Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes

Journal of Neurotrauma

Volumn 32, Issue 23, 2015, Pages 1834-1848

  Bramlett, Helen M ^a   Dietrich, W Dalton ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

atrophy; inflammation; neurogenesis; progressive damage; TBI; white matter

Indexed keywords

CALPAIN; INFLAMMASOME; INTERLEUKIN 1BETA; INTERLEUKIN 6; REACTIVE OXYGEN METABOLITE; TRANSFORMING GROWTH FACTOR; TUMOR NECROSIS FACTOR ALPHA;

APOPTOSIS; ARTICLE; BRAIN BLOOD FLOW; BRAIN ISCHEMIA; BRAIN REGION; CELLS; CYTOKINE PRODUCTION; DEGENERATIVE DISEASE; DEMYELINATING DISEASE; DIFFUSE AXONAL INJURY; EXCITOTOXICITY; HUMAN; INFLAMMATION; INFLAMMATORY CELL; MACROPHAGE; MOLECULAR PATHOLOGY; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEUROLOGICAL COMPLICATION; NEUROPATHOLOGY; NONHUMAN; OLIGODENDROGLIA; OXIDATIVE STRESS; POSTTRAUMATIC COMPLICATION; PROGNOSIS; PROTEIN DEGRADATION; SPREADING CORTICAL DEPRESSION; TRAUMATIC BRAIN INJURY; TRAUMATIC EPILEPSY; WHITE MATTER INJURY; BRAIN INJURY; COMPLICATION; PATHOLOGY;

BRAIN INJURY, CHRONIC; HUMANS;

EID: 84949815714     PISSN: 08977151     EISSN: 15579042     Source Type: Journal    
DOI: 10.1089/neu.2014.3352     Document Type: Article

References (262)

1. Masel, B.E., DeWitt, D.S. (2010). Traumatic brain injury: a disease process, not an event. J. Neurotrauma 27, 1529-1540.
2. Bergeson, A.G., Lundin, R., Parkinson, R.B., Tate, D.F., Victoroff, J., Hopkins, R.O., Bigler, E.D. (2004). Clinical rating of cortical atrophy and cognitive correlates following traumatic brain injury. Clin. Neuropsychol. 18, 509-520.
3. Levin, H.S., Amparo, E., Eisenberg, H.M., Williams, D.H., High, W.M., Jr., McArdle, C.B., Weiner, R.L. (1987). Magnetic resonance imaging and computerized tomography in relation to the neurobehavioral sequelae of mild and moderate head injuries. J. Neurosurg. 66, 706-713.
4. Corrigan, J.D., Hammond, F.M. (2013). Traumatic brain injury as a chronic health condition. Arch. Phys. Med. Rehabil. 94, 1199-1201.
5. Annegers, J.F., Hauser, W.A., Coan, S.P., Rocca, W.A. (1998). A population-based study of seizures after traumatic brain injuries. N. Engl. J. Med. 338, 20-24.
6. McLean, A., Jr., Dikmen, S., Temkin, N., Wyler, A.R., Gale, J.L. (1984). Psychosocial functioning at 1 month after head injury. Neurosurgery 14, 393-399.
7. Masel, B.E., Scheibel, R.S., Kimbark, T., Kuna, S.T. (2001). Excessive daytime sleepiness in adults with brain injuries. Arch. Phys. Med. Rehabil. 82, 1526-1532.
8. Lye, T.C., Shores, E.A. (2000). Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol. Rev. 10, 115-129.
9. Schneider, H.J., Kreitschmann-Andermahr, I., Ghigo, E., Stalla, G.K., Agha, A. (2007). Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 298, 1429-1438.
10. Goldman, S.M., Tanner, C.M., Oakes, D., Bhudhikanok, G.S., Gupta, A., Langston, J.W. (2006). Head injury and Parkinson's disease risk in twins. Ann. Neurol. 60, 65-72.
11. DeKosky, S.T., Blennow, K., Ikonomovic, M.D., Gandy, S. (2013). Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat. Rev. Neurol. 9, 192-200.
12. Institute of Medicine. (2009). Longterm consequences of traumatic brain injury, in: Gulf War and Health. The National Academies Press: Washington, D.C.
13. Vespa, P.M. (2013). Hormonal dysfunction in neurocritical patients. Curr. Opin. Crit. Care 19, 107-112.
14. Bramlett, H.M., Dietrich, W.D., Green, E.J., Busto, R. (1997). Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. Acta Neuropathol. (Berl.) 93, 190-199.
15. Atkins, C.M., Truettner, J.S., Lotocki, G., Sanchez-Molano, J., Kang, Y., Alonso, O.F., Sick, T.J., Dietrich, W.D., Bramlett, H.M. (2010). Post-traumatic seizure susceptibility is attenuated by hypothermia therapy. Eur. J. Neurosci. 32, 1912-1920.
16. Narayan, R.K., Michel, M.E., Ansell, B., Baethmann, A., Biegon, A., Bracken, M.B., Bullock, M.R., Choi, S.C., Clifton, G.L., Contant, C.F., Coplin, W.M., Dietrich, W.D., Ghajar, J., Grady, S.M., Grossman, R.G., Hall, E.D., Heetderks, W., Hovda, D.A., Jallo, J., Katz, R.L., Knoller, N., Kochanek, P.M., Maas, A.I., Majde, J., Marion, D.W., Marmarou, A., Marshall, L.F., McIntosh, T.K., Miller, E., Mohberg, N., Muizelaar, J.P., Pitts, L.H., Quinn, P., Riesenfeld, G., Robertson, C.S., Strauss, K.I., Teasdale, G., Temkin, N., Tuma, R., Wade, C., Walker, M.D., Weinrich, M., Whyte, J., Wilberger, J., Young, A.B., Yurkewicz, L. (2002). Clinical trials in head injury. J. Neurotrauma 19, 503-557.
17. Belur, P.K., Chang, J.J., He, S., Emanuel, B.A., Mack,W.J. (2013). Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury. Neurosurg. Focus 34, E9.
18. Lu, J., Gary, K.W., Neimeier, J.P., Ward, J., Lapane, K.L. (2012). Randomized controlled trials in adult traumatic brain injury. Brain Inj. 26, 1523-1548.
19. Uchino, H., Hatakeyama, K., Morota, S., Tanoue, T., Nishiyama, T., Usui, D., Taguchi, C., Suzuki, M., Hansson, M.J., Elmer, E. (2013). Cyclophilin-D inhibition in neuroprotection: dawn of a new era of mitochondrial medicine. Acta Neurochir. Suppl. 118, 311-315.
20. Xiong, Y., Mahmood, A., Chopp, M. (2013). Animal models of traumatic brain injury. Nat. Rev. Neurosci. 14, 128-142.
21. Loane, D.J., Faden, A.I. (2010). Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol. Sci. 31, 596-604.
22. Meng, Y., Xiong, Y., Mahmood, A., Zhang, Y., Qu, C., Chopp, M. (2011). Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats. J. Neurosurg. 115, 550-560.
23. Marklund, N., Hillered, L. (2011). Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here Br. J. Pharmacol. 164, 1207-1229.
24. Dashnaw, M.L., Petraglia, A.L., Bailes, J.E. (2012). An overview of the basic science of concussion and subconcussion: where we are and where we are going. Neurosurg. Focus 33, E5.
25. Rosenfeld, J.V., McFarlane, A.C., Bragge, P., Armonda, R.A., Grimes, J.B., Ling, G.S. (2013). Blast-related traumatic brain injury. Lancet Neurol. 12, 882-893.
26. McCrory, P., Meeuwisse, W.H., Aubry, M., Cantu, R.C., Dvorák, J., Echemendia, R.J., Engebretsen, L., Johnston, K.M., Kutcher, J.S., Raftery, M., Sills, A., Benson, B.W., Davis, G.A., Ellenbogen, R., Guskiewicz, K.M., Herring, S.A., Iverson, G.L., Jordan, B.D., Kissick, J., McCrea, M., McIntosh, A.S., Maddocks, D.L., Makdissi, M., Purcell, L., Putukian, M., Schneider, K., Tator, C.H., Turner, M. (2013). Consensus statement on concussion in sport-the 4th International Conference on Concussion in Sport held in Zurich, November 2012. PM R 5, 255-279.
27. Mouzon, B.C., Bachmeier, C., Ferro, A., Ojo, J.O., Crynen, G., Acker, C.M., Davies, P., Mullan, M., Stewart, W., Crawford, F. (2013). Chronic neuropathological and neurobehavioral changes in a repetitive mTBI model. Ann. Neurol. 75, 241-254.
28. Bramlett, H.M., Dietrich, W.D. (2002). Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol. (Berl.) 103, 607-614.
29. Bramlett, H.M., Dietrich, W.D. (2007). Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog. Brain Res. 161, 125-141.
30. Hall, E.D., Sullivan, P.G., Gibson, T.R., Pavel, K.M., Thompson, B.M., Scheff, S.W. (2005). Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal brain injury. J. Neurotrauma 22, 252-265.
31. Pierce, J.E., Smith, D.H., Trojanowski, J.Q., McIntosh, T.K. (1998). Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience 87, 359-369.
32. Smith, D.H., Chen, X.H., Pierce, J.E., Wolf, J.A., Trojanowski, J.Q., Graham, D.I., McIntosh, T.K. (1997). Progressive atrophy and neuron death for one year following brain trauma in the rat. J. Neurotrauma 14, 715-727.
33. Dixon, C.E., Kochanek, P.M., Yan, H.Q., Schiding, J.K., Griffith, R.G., Baum, E., Marion, D.W., DeKosky, S.T. (1999). One-year study of spatial memory performance, brain morphology, cholinergic markers after moderate controlled cortical impact in rats. J. Neurotrauma 16, 109-122.
34. Rodriguez-Paez, A.C., Brunschwig, J.P., Bramlett, H.M. (2005). Light and electron microscopic assessment of progressive atrophy following moderate traumatic brain injury in the rat. Acta Neuropathol. 109, 603-616.
35. van der Naalt, J., Hew, J.M., van Zomeren, A.H., Sluiter, W.J., Minderhoud, J.M. (1999). Computed tomography and magnetic resonance imaging in mild to moderate head injury: early and late imaging related to outcome. Ann. Neurol. 46, 70-78.
36. Hayasaki, K., Marmarou, A., Barzo, P., Fatouros, P., Corwin, F. (1997). Detection of brain atrophy following traumatic brain injury using gravimetric techniques. Acta Neurochir. Suppl. 70, 75-77.
37. Anderson, C.V., Bigler, E.D. (1995). Ventricular dilation, cortical atrophy, neuropsychological outcome following traumatic brain injury. J. Neuropsychiatry Clin. Neurosci. 7, 42-48.
38. Cullum, C.M., Bigler, E.D. (1986). Ventricle size, cortical atrophy and the relationship with neuropsychological status in closed head injury: a quantitative analysis. J. Clin. Exp. Neuropsychol. 8, 437-452.
39. Adnan, A., Crawley, A., Mikulis, D., Moscovitch, M., Colella, B., Green, R. (2013). Moderate-severe traumatic brain injury causes delayed loss of white matter integrity: evidence of fornix deterioration in the chronic stage of injury. Brain Inj. 27, 1415-1422.
40. Palacios, E.M., Sala-Llonch, R., Junque, C., Roig, T., Tormos, J.M., Bargallo, N., Vendrell, P. (2013). White matter/gray matter contrast changes in chronic and diffuse traumatic brain injury. J. Neurotrauma 30, 1991-1994.
41. Bigler, E.D., Maxwell, W.L. (2011). Neuroimaging and neuropathology of TBI. NeuroRehabilitation 28, 63-74.
42. Wang, K.K.W., Moghieb, A., Yang, Z., Zhang, Z. (2013). Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury, pps. 87230O-87230O-87215.
43. Bramlett, H.M. and Dietrich, W.D. (2004). Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J. Cereb. Blood Flow Metab. 24, 133-150.
44. Grossman, S.D., Wolfe, B.B., Yasuda, R.P., Wrathall, J.R. (1999). Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury. J. Neurosci. 19, 5711-5720.
45. McDonald, J.W., Althomsons, S.P., Hyrc, K.L., Choi, D.W., Goldberg, M.P. (1998). Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nat. Med. 4, 291-297.
46. Globus, M.Y., Alonso, O., Dietrich, W.D., Busto, R., Ginsberg, M.D. (1995). Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J. Neurochem. 65, 1704-1711.
47. Algattas, H., Huang, J.H. (2013). Traumatic brain injury pathophysiology and treatments: early, intermediate, late phases post-injury. Int. J. Mol. Sci. 15, 309-341.
48. Katayama, Y., Becker, D.P., Tamura, T., Hovda, D.A. (1990). Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J. Neurosurg. 73, 889-900.
49. Nilsson, P., Hillered, L., Ponten, U., Ungerstedt, U. (1990). Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J. Cereb. Blood Flow Metab. 10, 631-637.
50. Zauner, A., Bullock, R., Kuta, A.J., Woodward, J., Young, H.F. (1996). Glutamate release and cerebral blood flow after severe human head injury. Acta Neurochir. Suppl. 67, 40-44.
51. Faden, A.I., Demediuk, P., Panter, S.S., Vink, R. (1989). The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244, 798-800.
52. Hayes, R.L., Jenkins, L.W. and Lyeth, B.G. (1992). Neurotransmitter-mediated mechanisms of traumatic brain injury: acetylcholine and excitatory amino acids. J. Neurotrauma 9, Suppl. 1, S173-S187.
53. Palmer, A.M., Marion, D.W., Botscheller, M.L., Swedlow, P.E., Styren, S.D., DeKosky, S.T. (1993). Traumatic brain injuryinduced excitotoxicity assessed in a controlled cortical impact model. J. Neurochem. 61, 2015-2024.
54. Miller, L.P., Lyeth, B.G., Jenkins, L.W., Oleniak, L., Panchision, D., Hamm, R.J., Phillips, L.L., Dixon, C.E., Clifton, G.L., Hayes, R.L. (1990). Excitatory amino acid receptor subtype binding following traumatic brain injury. Brain Res/526, 103-107.
55. Bullock, R., Zauner, A., Myseros, J.S., Marmarou, A., Woodward, J.J. and Young, H.F. (1995). Evidence for prolonged release of excitatory amino acids in severe human head trauma. Relationship to clinical events. Ann. N. Y. Acad. Sci. 765, 290-297; discussion, 298.
56. Vespa, P., Prins, M., Ronne-Engstrom, E., Caron, M., Shalmon, E., Hovda, D.A., Martin, N.A. and Becker, D.P. (1998). Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study. J. Neurosurg. 89, 971-982.
57. Hutchinson, P.J. (2005). Microdialysis in traumatic brain injury-methodology and pathophysiology. Acta Neurochir. Suppl. 95, 441-445.
58. Hamm, R.J., O'Dell, D.M., Pike, B.R., Lyeth, B.G. (1993). Cognitive impairment following traumatic brain injury: the effect of pre-and post-injury administration of scopolamine and MK-801. Brain Res. Cogn. Brain Res. 1, 223-226.
59. Bullock, R., Kuroda, Y., Teasdale, G.M., McCulloch, J. (1992). Prevention of post-traumatic excitotoxic brain damage with NMDA antagonist drugs: a new strategy for the nineties. Acta Neurochir. Suppl. (Wien) 55, 49-55.
60. Shapira, Y., Yadid, G., Cotev, S., Niska, A., Shohami, E. (1990). Protective effect of MK801 in experimental brain injury. J. Neurotrauma 7, 131-139.
61. Avramescu, S., Nita, D.A., Timofeev, I. (2009). Neocortical post-traumatic epileptogenesis is associated with loss of GABAergic neurons. J. Neurotrauma 26, 799-812.
62. Waxman, S.G. (1989). Demyelination in spinal cord injury. J. Neurol. Sci. 91, 1-14.
63. Matute, C., Ransom, B.R. (2012). Roles of white matter in central nervous system pathophysiologies. ASN Neuro 4. pii: e00079. doi: 10.1042/AN20110060.
64. Shohami, E., Biegon, A. (2014). Novel approach to the role of NMDA receptors in traumatic brain injury. CNS Neurol. Disord. Drug Targets 13, 567-573.
65. Bains, M., Hall, E.D. (2012). Antioxidant therapies in traumatic brain and spinal cord injury. Biochim. Biophys. Acta 1822, 675-684.
66. Cornelius, C., Crupi, R., Calabrese, V., Graziano, A., Milone, P., Pennisi, G., Radak, Z., Calabrese, E.J., Cuzzocrea, S. (2013). Traumatic brain injury: oxidative stress and neuroprotection. Antioxid. Redox Signal. 19, 836-853.
67. Kontos, H.A., Wei, E.P., Ellis, E.F., Dietrich, W.D., Povlishock, J.T. (1981). Prostaglandins in physiological and in certain pathological responses of the cerebral circulation. Fed. Proc. 40, 2326-2330.
68. Rodriguez-Rodriguez, A., Egea-Guerrero, J.J., Murillo-Cabezas, F., Carrillo-Vico, A. (2014). Oxidative stress in traumatic brain injury. Curr. Med. Chem. 21, 1201-1211.
69. Hall, E.D., Wang, J.A., Miller, D.M. (2012). Relationship of nitric oxide synthase induction to peroxynitrite-mediated oxidative damage during the first week after experimental traumatic brain injury. Exp. Neurol. 238, 176-182.
70. Tewari, A., Mahendru, V., Sinha, A., Bilotta, F. (2014). Antioxidants: the new frontier for translational research in cerebroprotection. J. Anaesthesiol. Clin. Pharmacol. 30, 160-171.
71. Singh, I.N., Gilmer, L.K., Miller, D.M., Cebak, J.E., Wang, J.A., Hall, E.D. (2013). Phenelzine mitochondrial functional preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation-derived aldehyde 4-hydroxy-2-nonenal. J. Cereb. Blood Flow Metab. 33, 593-599.
72. Hughes, R.H., Silva, V.A., Ahmed, I., Shreiber, D.I., Morrison, B., III. (2014). Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures. Brain Res. 1543, 308-314.
73. Clond, M.A., Lee, B.S., Yu, J.J., Singer, M.B., Amano, T., Lamb, A.W., Drazin, D., Kateb, B., Ley, E.J., Yu, J.S. (2013). Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice. PloS One 8, e61819.
74. Stoica, B.A., Loane, D.J., Zhao, Z., Kabadi, S.V., Hanscom, M., Byrnes, K.R., Faden, A.I. (2014). PARP-1 inhibition attenuates neuronal loss, microglia activation and neurological deficits after traumatic brain injury. J. Neurotrauma 31, 758-772.
75. Di Pietro, V., Lazzarino, G., Amorini, A.M., Tavazzi, B., D'Urso, S., Longo, S., Vagnozzi, R., Signoretti, S., Clementi, E., Giardina, B., Lazzarino, G., Belli, A. (2014). Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat. Free Radic. Biol. Med. 69, 258-264.
76. Miller, D.M., Singh, I.N., Wang, J.A., Hall, E.D. (2013). Administration of the Nrf2-ARE activators sulforaphane and carnosic acid attenuates 4-hydroxy-2-nonenal-induced mitochondrial dysfunction ex vivo. Free Radic. Biol. Med. 57, 1-9.
77. Miller, D.M., Wang, J.A., Buchanan, A.K., Hall, E.D. (2014). Temporal and spatial dynamics of nrf2-antioxidant response elements mediated gene targets in cortex and hippocampus after controlled cortical impact traumatic brain injury in mice. J. Neurotrauma 31, 1194-1201.
78. Keane, R.W., Kraydieh, S., Lotocki, G., Alonso, O.F., Aldana, P., Dietrich, W.D. (2001). Apoptotic and antiapoptotic mechanisms after traumatic brain injury. J. Cereb. Blood Flow Metab. 21, 1189-1198.
79. Eldadah, B.A., Faden, A.I. (2000). Caspase pathways, neuronal apoptosis, CNS injury. J. Neurotrauma 17, 811-829.
80. Uzan, M., Erman, H., Tanriverdi, T., Sanus, G.Z., Kafadar, A., Uzun, H. (2006). Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury. Acta Neurochir. (Wien) 148, 1157-1164; discussion.
81. Wagner, A.K., Amin, K.B., Niyonkuru, C., Postal, B.A., McCullough, E.H., Ozawa, H., Dixon, C.E., Bayir, H., Clark, R.S., Kochanek, P.M., Fabio, A. (2011). CSF Bcl-2 and cytochrome C temporal profiles in outcome prediction for adults with severe TBI. J. Cereb. Blood Flow Metab. 31, 1886-1896.
82. Raghupathi, R. (2004). Cell death mechanisms following traumatic brain injury. Brain Pathol. 14, 215-222.
83. Flygt, J., Djupsjo, A., Lenne, F., Marklund, N. (2013). Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat. Eur. J. Neurosci. 38, 2153-2165.
84. Lotocki, G., de Rivero Vaccari, J.P., Alonso, O., Molano, J.S., Nixon, R., Safavi, P., Dietrich, W.D., Bramlett, H.M. (2011). Oligodendrocyte vulnerability following traumatic brain injury in rats. Neurosci. Lett. 499, 143-148.
85. Yakovlev, A.G., Faden, A.I. (2001). Caspase-dependent apoptotic pathways in CNS injury. Mol. Neurobiol. 24, 131-144.
86. Zhang, X., Chen, Y., Jenkins, L.W., Kochanek, P.M., Clark, R.S. (2005). Bench-to-bedside review: apoptosis/programmed cell death triggered by traumatic brain injury. Critical Care (Lond.) 9, 66-75.
87. Knoblach, S.M., Nikolaeva, M., Huang, X., Fan, L., Krajewski, S., Reed, J.C., Faden, A.I. (2002). Multiple caspases are activated after traumatic brain injury: evidence for involvement in functional outcome. J. Neurotrauma 19, 1155-1170.
88. Clark, R.S., Kochanek, P.M., Watkins, S.C., Chen, M., Dixon, C.E., Seidberg, N.A., Melick, J., Loeffert, J.E., Nathaniel, P.D., Jin, K.L., Graham, S.H. (2000). Caspase-3 mediated neuronal death after traumatic brain injury in rats. J. Neurochem 74, 740-753.
89. Satchell, M.A., Zhang, X., Kochanek, P.M., Dixon, C.E., Jenkins, L.W., Melick, J., Szabo, C., Clark, R.S. (2003). A dual role for poly-ADP-ribosylation in spatial memory acquisition after traumatic brain injury in mice involving NAD+ depletion and ribosylation of 14-3-3gamma. J. Neurochem. 85, 697-708.
90. Wong, J., Hoe, N.W., Zhiwei, F., Ng, I. (2005). Apoptosis and traumatic brain injury. Neurocrit. Care 3, 177-182.
91. Das, M., Mohapatra, S., Mohapatra, S.S. (2012). New perspectives on central and peripheral immune responses to acute traumatic brain injury. J. Neuroinflammation 9, 236.
92. Loane, D.J., Kumar, A., Stoica, B.A., Cabatbat, R., Faden, A.I. (2014). Progressive neurodegeneration after experimental brain trauma: association with chronic microglial activation. J. Neuropathol. Exp. Neurol. 73, 14-29.
93. Ziebell, J.M., Morganti-Kossmann, M.C. (2010). Involvement of pro-and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 7, 22-30.
94. Smith, C., Gentleman, S.M., Leclercq, P.D., Murray, L.S., Griffin, W.S., Graham, D.I., Nicoll, J.A. (2013). The neuroinflammatory response in humans after traumatic brain injury. Neuropathol. Appl. Neurobiol. 39, 654-666.
95. Mayer, C.L., Huber, B.R., Peskind, E. (2013). Traumatic brain injury, neuroinflammation, post-traumatic headaches. Headache 53, 1523-1530.
96. Gentleman, S.M., Leclercq, P.D., Moyes, L., Graham, D.I., Smith, C., Griffin, W.S., Nicoll, J.A. (2004). Long-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci. Int. 146, 97-104.
97. Nonaka, M., Chen, X.H., Pierce, J.E., Leoni, M.J., McIntosh, T.K., Wolf, J.A., Smith, D.H. (1999). Prolonged activation of NFkappaB following traumatic brain injury in rats. J. Neurotrauma 16, 1023-1034.
98. Acosta, S.A., Tajiri, N., Shinozuka, K., Ishikawa, H., Grimmig, B., Diamond, D., Sanberg, P.R., Bickford, P.C., Kaneko, Y., Borlongan, C.V. (2013). Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model. PloS One 8, e53376.
99. Morganti-Kossmann, M.C., Rancan, M., Stahel, P.F., Kossmann, T. (2002). Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr. Opin. Crit. Care 8, 101-105.
100. de Rivero Vaccari, J.P., Dietrich, W.D., Keane, R.W. (2014). Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J. Cereb. Blood Flow Metab. 34, 369-375.
101. de Rivero Vaccari, J.P., Lotocki, G., Marcillo, A.E., Dietrich, W.D., Keane, R.W. (2008). A molecular platform in neurons regulates inflammation after spinal cord injury. J. Neurosci. 28, 3404-3414.
102. Adamczak, S., Dale, G., de Rivero Vaccari, J.P., Bullock, M.R., Dietrich, W.D., Keane, R.W. (2012). Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article. J. Neurosurg. 117, 1119-1125.
103. Siman, R., Giovannone, N., Hanten, G., Wilde, E.A., McCauley, S.R., Hunter, J.V., Li, X., Levin, H.S., Smith, D.H. (2013). Evidence that the blood biomarker SNTF predicts brain imaging changes and persistent cognitive dysfunction in mild TBI patients. Front. Neurol. 4, 190.
104. McClain, C.J., Cohen, D., Ott, L., Dinarello, C.A., Young, B. (1987). Ventricular fluid interleukin-1 activity in patients with head injury. J. Lab. Clin. Med. 110, 48-54.
105. Frugier, T., Morganti-Kossmann, M.C., O'Reilly, D., McLean, C.A. (2010). In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J. Neurotrauma 27, 497-507.
106. Johnson, V.E., Stewart, J.E., Begbie, F.D., Trojanowski, J.Q., Smith, D.H., Stewart, W. (2013). Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 136, 28-42.
107. Ramlackhansingh, A.F., Brooks, D.J., Greenwood, R.J., Bose, S.K., Turkheimer, F.E., Kinnunen, K.M., Gentleman, S., Heckemann, R.A., Gunanayagam, K., Gelosa, G., Sharp, D.J. (2011). Inflammation after trauma: microglial activation and traumatic brain injury. Ann. Neurol. 70, 374-383.
108. Singh, N., Hopkins, S.J., Hulme, S., Galea, J.P., Hoadley, M., Vail, A., Hutchinson, P.J., Grainger, S., Rothwell, N.J., King, A.T., Tyrrell, P.J. (2014). The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J. Neuroinflammation 11, 1.
109. Tehranian, R., Andell-Jonsson, S., Beni, S.M., Yatsiv, I., Shohami, E., Bartfai, T., Lundkvist, J., Iverfeldt, K. (2002). Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin-1 receptor antagonist. J. Neurotrauma 19, 939-951.
110. Lucas, S.M., Rothwell, N.J., Gibson, R.M. (2006). The role of inflammation in CNS injury and disease. Br. J. Pharmacol. 147, Suppl. 1, S232-S240.
111. Jones, N.C., Prior, M.J., Burden-Teh, E., Marsden, C.A., Morris, P.G., Murphy, S. (2005). Antagonism of the interleukin-1 receptor following traumatic brain injury in the mouse reduces the number of nitric oxide synthase-2-positive cells and improves anatomical and functional outcomes. Eur. J. Neurosci. 22, 72-78.
112. Adamczak, S.E., de Rivero Vaccari, J.P., Dale, G., Brand Iii, F.J., Nonner, D., Bullock, M., Dahl, G.P., Dietrich, W., Keane, R.W. (2014). Pyroptotic neuronal cell death mediated by the AIM2 inflammasome. J. Cereb. Blood Flow Metab. 34, 621-629.
113. Clausen, F., Hanell, A., Bjork, M., Hillered, L., Mir, A.K., Gram, H., Marklund, N. (2009). Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice. Eur. J. Neurosci. 30, 385-396.
114. Clausen, F., Hanell, A., Israelsson, C., Hedin, J., Ebendal, T., Mir, A.K., Gram, H., Marklund, N. (2011). Neutralization of interleukin-1beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice. Eur. J. Neurosci. 34, 110-123.
115. Xiao, G., Wei, J., Yan, W., Wang, W., Lu, Z. (2008). Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit. Care (Lond.) 12, R61.
116. Dietrich, W.D., Atkins, C.M., Bramlett, H.M. (2009). Protection in animal models of brain and spinal cord injury with mild to moderate hypothermia. J. Neurotrauma 26, 301-312.
117. Chatzipanteli, K., Alonso, O.F., Kraydieh, S., Dietrich, W.D. (2000). Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies. J. Cereb. Blood Flow Metab. 20, 531-542.
118. Chatzipanteli, K., Yanagawa, Y., Marcillo, A.E., Kraydieh, S., Yezierski, R.P., Dietrich, W.D. (2000). Posttraumatic hypothermia reduces polymorphonuclear leukocyte accumulation following spinal cord injury in rats. J. Neurotrauma 17, 321-332.
119. Kinoshita, K., Chatzipanteli, K., Vitarbo, E., Truettner, J.S., Alonso, O.F., Dietrich, W.D. (2002). Interleukin-1beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature. Neurosurgery 51, 195-203; discussion, 203.
120. Vitarbo, E.A., Chatzipanteli, K., Kinoshita, K., Truettner, J.S., Alonso, O.F., Dietrich, W.D. (2004). Tumor necrosis factor alpha expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature. Neurosurgery 55, 416-424; discussion, 424-415.
121. Tomura, S., de Rivero Vaccari, J.P., Keane, R.W., Bramlett, H.M., Dietrich, W.D. (2012). Effects of therapeutic hypothermia on inflammasome signaling after traumatic brain injury. J. Cereb. Blood Flow Metab. 32, 1939-1947.
122. Dietrich, W.D. (1992). The importance of brain temperature in cerebral injury. J. Neurotrauma 9, Suppl. 2, S475-S485.
123. Gensel, J.C., Kigerl, K.A., Mandrekar-Colucci, S.S., Gaudet, A.D., Popovich, P.G. (2012). Achieving CNS axon regeneration by manipulating convergent neuro-immune signaling. Cell Tissue Res. 349, 201-213.
124. Kigerl, K.A., Gensel, J.C., Ankeny, D.P., Alexander, J.K., Donnelly, D.J., Popovich, P.G. (2009). Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci. 29, 13435-13444.
125. Donnelly, D.J., Gensel, J.C., Ankeny, D.P., van Rooijen, N., Popovich, P.G. (2009). An efficient and reproducible method for quantifying macrophages in different experimental models of central nervous system pathology. J. Neurosci. Methods 181, 36-44.
126. Chhor, V., Le Charpentier, T., Lebon, S., Ore, M.V., Celador, I.L., Josserand, J., Degos, V., Jacotot, E., Hagberg, H., Savman, K., Mallard, C., Gressens, P., Fleiss, B. (2013). Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav. Immun. 32, 70-85.
127. Hu, X., Li, P., Guo, Y., Wang, H., Leak, R.K., Chen, S., Gao, Y., Chen, J. (2012). Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke 43, 3063-3070.
128. Jetten, N., Verbruggen, S., Gijbels, M.J., Post, M.J., De Winther, M.P., Donners, M.M. (2014). Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17, 109-118.
129. Fenn, A.M., Gensel, J.C., Huang, Y., Popovich, P.G., Lifshitz, J., Godbout, J.P. (2013). Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia. Biol. Psychiatry 76, 575-584.
130. Lowenstein, D.H. (2009). Epilepsy after head injury: an overview. Epilepsia 50, Suppl. 2, 4-9.
131. Vespa, P.M., Nuwer, M.R., Nenov, V., Ronne-Engstrom, E., Hovda, D.A., Bergsneider, M., Kelly, D.F., Martin, N.A., Becker, D.P. (1999). Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J. Neurosurg. 91, 750-760.
132. Bushnik, T., Englander, J., Wright, J., Kolakowsky-Hayner, S.A. (2012). Traumatic brain injury with and without late posttraumatic seizures: what are the impacts in the post-acute phase: a NIDRR Traumatic Brain Injury Model Systems study. J. Head Trauma Rehabil. 27, E36-E44.
133. Asikainen, I., Kaste, M., Sarna, S. (1999). Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia 40, 584-589.
134. Garga, N., Lowenstein, D.H. (2006). Posttraumatic epilepsy: a major problem in desperate need of major advances. Epilepsy Curr. 6, 1-5.
135. Bao, Y.H., Bramlett, H.M., Atkins, C.M., Truettner, J.S., Lotocki, G., Alonso, O.F., Dietrich, W.D. (2011). Post-traumatic seizures exacerbate histopathological damage after fluid-percussion brain injury. J. Neurotrauma 28, 35-42.
136. Kharatishvili, I., Nissinen, J.P., McIntosh, T.K., Pitkanen, A. (2006). A model of posttraumatic epilepsy induced by lateral fluidpercussion brain injury in rats. Neuroscience 140, 685-697.
137. Santhakumar, V., Ratzliff, A.D., Jeng, J., Toth, Z., Soltesz, I. (2001). Long-term hyperexcitability in the hippocampus after experimental head trauma. Ann. Neurol. 50, 708-717.
138. Stewart, T.H., Eastman, C.L., Groblewski, P.A., Fender, J.S., Verley, D.R., Cook, D.G., D'Ambrosio, R. (2010). Chronic dysfunction of astrocytic inwardly rectifying K+ channels specific to the neocortical epileptic focus after fluid percussion injury in the rat. J. Neurophysiol. 104, 3345-3360.
139. Ueda, Y., Kitamoto, A., Willmore, L.J., Kojima, T. (2011). Hippocampal gene network analysis in an experimental model of posttraumatic epilepsy. Neurochem. Res. 36, 1323-1328.
140. Arndt, D.H., Lerner, J.T., Matsumoto, J.H., Madikians, A., Yudovin, S., Valino, H., McArthur, D.L., Wu, J.Y., Leung, M., Buxey, F., Szeliga, C., Van Hirtum-Das, M., Sankar, R., Brooks-Kayal, A., Giza, C.C. (2013). Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort. Epilepsia 54, 1780-1788.
141. Temkin, N.R. (2009). Preventing and treating posttraumatic seizures: the human experience. Epilepsia 50, Suppl. 2, 10-13.
142. Pearl, P.L., McCarter, R., McGavin, C.L., Yu, Y., Sandoval, F., Trzcinski, S., Atabaki, S.M., Tsuchida, T., van den Anker, J., He, J., Klein, P. (2013). Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy. Epilepsia 54, e135-e137.
143. Sick, J., Bray, E., Bregy, A., Dietrich, W.D., Bramlett, H.M., Sick, T. (2013). EEGgui: a program used to detect electroencephalogram anomalies after traumatic brain injury. Source Code Biol. Med. 8, 12.
144. Vespa, P.M., McArthur, D.L., Xu, Y., Eliseo, M., Etchepare, M., Dinov, I., Alger, J., Glenn, T.P., Hovda, D. (2010). Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 75, 792-798.
145. Lu, X.C., Mountney, A., Chen, Z., Wei, G., Cao, Y., Leung, L.Y., Khatri, V., Cunningham, T., Tortella, F.C. (2013). Similarities and differences of acute nonconvulsive seizures and other epileptic activities following penetrating and ischemic brain injuries in rats. J. Neurotrauma 30, 580-590.
146. Hartings, J.A., Strong, A.J., Fabricius, M., Manning, A., Bhatia, R., Dreier, J.P., Mazzeo, A.T., Tortella, F.C., Bullock, M.R.; Co-Operative Study of Brain Injury Depolarizations. (2009). Spreading depolarizations and late secondary insults after traumatic brain injury. J. Neurotrauma 26, 1857-1866.
147. Alessandri, B., Tretzel, J.S., Heimann, A., Kempski, O. (2012). Spontaneous cortical spreading depression and intracranial pressure following acute subdural hematoma in a rat. Acta Neurochir. Suppl. 114, 373-376.
148. Dreier, J.P. (2011). The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat. Med. 17, 439-447.
149. Dreier, J.P., Major, S., Pannek, H.W., Woitzik, J., Scheel, M., Wiesenthal, D., Martus, P., Winkler, M.K., Hartings, J.A., Fabricius, M., Speckmann, E.J., Gorji, A.; COSBID Study Group. (2012). Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex. Brain 135, 259-275.
150. Dohmen, C., Sakowitz, O.W., Fabricius, M., Bosche, B., Reithmeier, T., Ernestus, R.I., Brinker, G., Dreier, J.P., Woitzik, J., Strong, A.J., Graf, R.; Co-Operative Study of Brain Injury Depolarizations (COSBID). (2008). Spreading depolarizations occur in human ischemic stroke with high incidence. Ann. Neurol. 63, 720-728.
151. Menniti, F.S., Pagnozzi, M.J., Butler, P., Chenard, B.L., Jaw-Tsai, S.S., Frost White, W. (2000). CP-101,606, an NR2B subunit selective NMDA receptor antagonist, inhibits NMDA and injury induced c-fos expression and cortical spreading depression in rodents. Neuropharmacology 39, 1147-1155.
152. Hertle, D.N., Dreier, J.P., Woitzik, J., Hartings, J.A., Bullock, R., Okonkwo, D.O., Shutter, L.A., Vidgeon, S., Strong, A.J., Kowoll, C., Dohmen, C., Diedler, J., Veltkamp, R., Bruckner, T., Unterberg, A.W., Sakowitz, O.W., Cooperative Study of Brain Injury, D. (2012). Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury. Brain 135, 2390-2398.
153. Piilgaard, H., Witgen, B.M., Rasmussen, P., Lauritzen, M. (2011). Cyclosporine A, FK506, NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression. J. Cereb. Blood Flow Metab. 31, 1588-1598.
154. Yenari, M.A., Onley, D., Hedehus, M., deCrespigny, A., Sun, G.H., Moseley, M.E., Steinberg, G.K. (2000). Diffusion-and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under conditions of mild hypothermia. Brain Res. 885, 208-219.
155. Katsura, K., Minamisawa, H., Ekholm, A., Folbergrova, J., Siesjo, B.K. (1992). Changes of labile metabolites during anoxia in moderately hypo-and hyperthermic rats: correlation to membrane fluxes of K+ . Brain Res. 590, 6-12.
156. Willmore, L.J. (2012). Posttraumatic epilepsy: what's contusion got to do with it Epilepsy Curr. 12, 87-91.
157. Willmore, L.J., Ueda, Y. (2009). Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate. Neurochem. Res. 34, 688-697.
158. Ueda, Y., Kitamoto, A., Willmore, L.J., Kojima, T. (2013). Hippocampal gene expression profiling in a rat model of posttraumatic epilepsy reveals temporal upregulation of lipid metabolismrelated genes. Neurochem. Res. 38, 1399-1406.
159. Schoch, K.M., von Reyn, C.R., Bian, J., Telling, G.C., Meaney, D.F., Saatman, K.E. (2013). Brain injury-induced proteolysis is reduced in a novel calpastatin-overexpressing transgenic mouse. J. Neurochem. 125, 909-920.
160. Ottens, A.K., Golden, E.C., Bustamante, L., Hayes, R.L., Denslow, N.D., Wang, K.K. (2008). Proteolysis of multiple myelin basic protein isoforms after neurotrauma: characterization by mass spectrometry. J. Neurochem. 104, 1404-1414.
161. Reeves, T.M., Greer, J.E., Vanderveer, A.S., Phillips, L.L. (2010). Proteolysis of submembrane cytoskeletal proteins ankyrin-G and alphaII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain. Pathol. 20, 1055-1068.
162. Thompson, S.N., Gibson, T.R., Thompson, B.M., Deng, Y., Hall, E.D. (2006). Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice. Exp. Neurol. 201, 253-265.
163. Liu, M.C., Akle, V., Zheng, W., Dave, J.R., Tortella, F.C., Hayes, R.L., Wang, K.K. (2006). Comparing calpain-and caspase-3-mediated degradation patterns in traumatic brain injury by differential proteome analysis. Biochem. J. 394, 715-725.
164. Ma, M., Shofer, F.S., Neumar, R.W. (2012). Calpastatin overexpression protects axonal transport in an in vivo model of traumatic axonal injury. J. Neurotrauma 29, 2555-2563.
165. Brophy, G.M., Pineda, J.A., Papa, L., Lewis, S.B., Valadka, A.B., Hannay, H.J., Heaton, S.C., Demery, J.A., Liu, M.C., Tepas, J.J., III, Gabrielli, A., Robicsek, S., Wang, K.K., Robertson, C.S., Hayes, R.L. (2009). alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury. J. Neurotrauma 26, 471-479.
166. Ma, M., Li, L., Wang, X., Bull, D.L., Shofer, F.S., Meaney, D.F., Neumar, R.W. (2012). Short-duration treatment with the calpain inhibitor MDL-28170 does not protect axonal transport in an in vivo model of traumatic axonal injury. J. Neurotrauma 29, 445-451.
167. Czeiter, E., Buki, A., Bukovics, P., Farkas, O., Pal, J., Kovesdi, E., Doczi, T., Sandor, J. (2009). Calpain inhibition reduces axolemmal leakage in traumatic axonal injury. Molecules 14, 5115-5123.
168. Schoch, K.M., Evans, H.N., Brelsfoard, J.M., Madathil, S.K., Takano, J., Saido, T.C., Saatman, K.E. (2012). Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury. Exp. Neurol. 236, 371-382.
169. Povlishock, J.T., Christman, C.W. (1995). The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J. Neurotrauma 12, 555-564.
170. Bramlett, H.M., Kraydieh, S., Green, E.J., Dietrich, W.D. (1997). Temporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats. J. Neuropathol. Exp. Neurol. 56, 1132-1141.
171. Pierce, J.E., Trojanowski, J.Q., Graham, D.I., Smith, D.H., McIntosh, T.K. (1996). Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and betaamyloid peptide after experimental brain injury in the rat. J. Neurosci. 16, 1083-1090.
172. Johnson, V.E., Stewart, W., Smith, D.H. (2013). Axonal pathology in traumatic brain injury. Exp. Neurol. 246, 35-43.
173. Greenberg, G., Mikulis, D.J., Ng, K., DeSouza, D., Green, R.E. (2008). Use of diffusion tensor imaging to examine subacute white matter injury progression in moderate to severe traumatic brain injury. Arch. Phys. Med. Rehabil. 89, S45-S50.
174. Hall, E.D., Bryant, Y.D., Cho, W. and Sullivan, P.G. (2008). Evolution of post-traumatic neurodegeneration after controlled cortical impact traumatic brain injury in mice and rats as assessed by the de Olmos silver and fluorojade staining methods. J. Neurotrauma 25, 235-247.
175. Hemerka, J.N., Wu, X., Dixon, C.E., Garman, R.H., Exo, J.L., Shellington, D.K., Blasiole, B., Vagni, V.A., Janesko-Feldman, K., Xu, M., Wisniewski, S.R., Bayir, H., Jenkins, L.W., Clark, R.S., Tisherman, S.A., Kochanek, P.M. (2012). Severe brief pressurecontrolled hemorrhagic shock after traumatic brain injury exacer-bates functional deficits and long-term neuropathological damage in mice. J. Neurotrauma 29, 2192-2208.
176. Adams, J.H., Graham, D.I., Jennett, B. (2000). The neuropathology of the vegetative state after an acute brain insult. Brain 123, Pt. 7, 1327-1338.
177. Graham, D.I., Adams, J.H., Nicoll, J.A., Maxwell, W.L., Gennarelli, T.A. (1995). The nature, distribution and causes of traumatic brain injury. Brain Pathol. 5, 397-406.
178. Povlishock, J.T. (1992). Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol. 2, 1-12.
179. Conti, A.C., Raghupathi, R., Trojanowski, J.Q., McIntosh, T.K. (1998). Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. J. Neurosci. 18, 5663-5672.
180. Sutula, T., He, X.X., Cavazos, J., Scott, G. (1988). Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science 239, 1147-1150.
181. Swartz, B.E., Houser, C.R., Tomiyasu, U., Walsh, G.O., DeSalles, A., Rich, J.R., Delgado-Escueta, A. (2006). Hippocampal cell loss in posttraumatic human epilepsy. Epilepsia 47, 1373-1382.
182. Santhakumar, V., Bender, R., Frotscher, M., Ross, S.T., Hollrigel, G.S., Toth, Z., Soltesz, I. (2000). Granule cell hyperexcitability in the early post-traumatic rat dentate gyrus: the 'irritable mossy cell' hypothesis. J. Physiol. 524, Pt. 1, 117-134.
183. Golarai, G., Greenwood, A.C., Feeney, D.M., Connor, J.A. (2001). Physiological and structural evidence for hippocampal involvement in persistent seizure susceptibility after traumatic brain injury. J. Neurosci. 21, 8523-8537.
184. Greer, J.E., McGinn, M.J., Povlishock, J.T. (2011). Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, axonal outgrowth in the axotomized neuronal population. J. Neurosci. 31, 5089-5105.
185. Kharatishvili, I., Immonen, R., Grohn, O., Pitkanen, A. (2007). Quantitative diffusion MRI of hippocampus as a surrogate marker for post-traumatic epileptogenesis. Brain 130, 3155-3168.
186. Dickson, T.C., Chung, R.S., McCormack, G.H., Staal, J.A., Vickers, J.C. (2007). Acute reactive and regenerative changes in mature cortical axons following injury. Neuroreport 18, 283-288.
187. Babb, T.L., Kupfer, W.R., Pretorius, J.K., Crandall, P.H., Levesque, M.F. (1991). Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience 42, 351-363.
188. Fujita, M., Oda, Y., Wei, E.P., Povlishock, J.T. (2011). The combination of either tempol or FK506 with delayed hypothermia: implications for traumatically induced microvascular and axonal protection. J. Neurotrauma 28, 1209-1218.
189. Buki, A., Koizumi, H., Povlishock, J.T. (1999). Moderate posttraumatic hypothermia decreases early calpain-mediated proteolysis and concomitant cytoskeletal compromise in traumatic axonal injury. Exp. Neurol. 159, 319-328.
190. Ma, M., Matthews, B.T., Lampe, J.W., Meaney, D.F., Shofer, F.S., Neumar, R.W. (2009). Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. Exp. Neurol. 215, 119-127.
191. Maxwell, W.L., Watson, A., Queen, R., Conway, B., Russell, D., Neilson, M., Graham, D.I. (2005). Slow, medium, or fast rewarming following post-traumatic hypothermia therapy An ultrastructural perspective. J. Neurotrauma 22, 873-884.
192. Kumar, R., Husain, M., Gupta, R.K., Hasan, K.M., Haris, M., Agarwal, A.K., Pandey, C.M., Narayana, P.A. (2009). Serial changes in the white matter diffusion tensor imaging metrics in moderate traumatic brain injury and correlation with neuro-cognitive function. J. Neurotrauma 26, 481-495.
193. Fields, R.D. (2008). White matter in learning, cognition and psychiatric disorders. Trends Neurosci. 31, 361-370.
194. Zhao, C., Deng, W., Gage, F.H. (2008). Mechanisms and functional implications of adult neurogenesis. Cell 132, 645-660.
195. Zhao, C., Teng, E.M., Summers, R.G., Jr., Ming, G.L., Gage, F.H. (2006). Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J. Neurosci. 26, 3-11.
196. Deng, W., Aimone, J.B., Gage, F.H. (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory Nat. Rev. Neurosci. 11, 339-350.
197. Dupret, D., Revest, J.M., Koehl, M., Ichas, F., De Giorgi, F., Costet, P., Abrous, D.N., Piazza, P.V. (2008). Spatial relational memory requires hippocampal adult neurogenesis. PloS One 3, e1959.
198. Gould, E., Beylin, A., Tanapat, P., Reeves, A., Shors, T.J. (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2, 260-265.
199. Spalding, K.L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H.B., Bostrom, E., Westerlund, I., Vial, C., Buchholz, B.A., Possnert, G., Mash, D.C., Druid, H., Frisen, J. (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219-1227.
200. Chirumamilla, S., Sun, D., Bullock, M.R., Colello, R.J. (2002). Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J. Neurotrauma 19, 693-703.
201. Dash, P.K., Mach, S.A., Moore, A.N. (2001). Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J. Neurosci. Res. 63, 313-319.
202. Sun, D., McGinn, M.J., Zhou, Z., Harvey, H.B., Bullock, M.R., Colello, R.J. (2007). Anatomical integration of newly generated dentate granule neurons following traumatic brain injury in adult rats and its association to cognitive recovery. Exp. Neurol. 204, 264-272.
203. Gao, X., Enikolopov, G., Chen, J. (2009). Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus. Exp. Neurol. 219, 516-523.
204. Urrea, C., Castellanos, D.A., Sagen, J., Tsoulfas, P., Bramlett, H.M., Dietrich, W.D. (2007). Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat. Restor. Neurol. Neurosci. 25, 65-76.
205. Chen, X.H., Iwata, A., Nonaka, M., Browne, K.D., Smith, D.H. (2003). Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in rats. J. Neurotrauma 20, 623-631.
206. Bregy, A., Nixon, R., Lotocki, G., Alonso, O.F., Atkins, C.M., Tsoulfas, P., Bramlett, H.M., Dietrich, W.D. (2012). Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat. Exp. Neurol. 233, 821-828.
207. Blaiss, C.A., Yu, T.S., Zhang, G., Chen, J., Dimchev, G., Parada, L.F., Powell, C.M., Kernie, S.G. (2011). Temporally specified genetic ablation of neurogenesis impairs cognitive recovery after traumatic brain injury. J. Neurosci. 31, 4906-4916.
208. Gao, X., Deng-Bryant, Y., Cho, W., Carrico, K.M., Hall, E.D., Chen, J. (2008). Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury. J. Neurosci. Res. 86, 2258-2270.
209. Sierra, A., Encinas, J.M., Deudero, J.J., Chancey, J.H., Enikolopov, G., Overstreet-Wadiche, L.S., Tsirka, S.E., Maletic-Savatic, M. (2010). Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7, 483-495.
210. Barha, C.K., Ishrat, T., Epp, J.R., Galea, L.A., Stein, D.G. (2011). Progesterone treatment normalizes the levels of cell proliferation and cell death in the dentate gyrus of the hippocampus after traumatic brain injury. Exp. Neurol. 231, 72-81.
211. Blaya, M.O., Bramlett, H., Nadoo, J., Pieper, A.A., Dietrich, W.D., III. (2014). Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury. J. Neurotrauma 31, 476-496.
212. Zhang, Y., Chopp, M., Mahmood, A., Meng, Y., Qu, C., Xiong, Y. (2012). Impact of inhibition of erythropoietin treatment-mediated neurogenesis in the dentate gyrus of the hippocampus on restoration of spatial learning after traumatic brain injury. Exp. Neurol. 235, 336-344.
213. Gaulke, L.J., Horner, P.J., Fink, A.J., McNamara, C.L., Hicks, R.R. (2005). Environmental enrichment increases progenitor cell survival in the dentate gyrus following lateral fluid percussion injury. Brain Res. Mol. Brain Res. 141, 138-150.
214. Dietrich, W.D., Alonso, O., Busto, R., Prado, R., Dewanjee, S., Dewanjee, M.K., Ginsberg, M.D. (1996). Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats. J. Cereb. Blood Flow Metab. 16, 481-489.
215. Dietrich, W.D., Alonso, O., Busto, R., Prado, R., Zhao, W., Dewanjee, M.K., Ginsberg, M.D. (1998). Posttraumatic cerebral ischemia after fluid percussion brain injury: an autoradiographic and histopathological study in rats. Neurosurgery 43, 585-593; discussion, 593-584.
216. DeWitt, D.S., Jenkins, L.W., Wei, E.P., Lutz, H., Becker, D.P., Kontos, H.A. (1986). Effects of fluid-percussion brain injury on regional cerebral blood flow and pial arteriolar diameter. J. Neurosurg. 64, 787-794.
217. Bouma, G.J., Muizelaar, J.P., Choi, S.C., Newlon, P.G., Young, H.F. (1991). Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. J. Neurosurg. 75, 685-693.
218. Marion, D.W., Darby, J., Yonas, H. (1991). Acute regional cerebral blood flow changes caused by severe head injuries. J. Neurosurg. 74, 407-414.
219. Forbes, M.L., Hendrich, K.S., Kochanek, P.M., Williams, D.S., Schiding, J.K., Wisniewski, S.R., Kelsey, S.F., DeKosky, S.T., Graham, S.H., Marion, D.W., Ho, C. (1997). Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spinlabeling in rats. J. Cereb. Blood Flow Metab. 17, 865-874.
220. Bryan, R.M., Jr., Cherian, L., Robertson, C. (1995). Regional cerebral blood flow after controlled cortical impact injury in rats. Anesth. Analg. 80, 687-695.
221. Len, T.K., Neary, J.P. (2011). Cerebrovascular pathophysiology following mild traumatic brain injury. Clin. Physiol. Funct. Imaging 31, 85-93.
222. Ginsberg, M.D., Zhao, W., Alonso, O.F., Loor-Estades, J.Y., Dietrich, W.D., Busto, R. (1997). Uncoupling of local cerebral glucose metabolism and blood flow after acute fluid-percussion injury in rats. Am. J. Physiol. 272, H2859-H2868.
223. Bartnik, B.L., Hovda, D.A., Lee, P.W. (2007). Glucose metabolism after traumatic brain injury: estimation of pyruvate carboxylase and pyruvate dehydrogenase flux by mass isotopomer analysis. J. Neurotrauma 24, 181-194.
224. Wu, H.M., Huang, S.C., Vespa, P., Hovda, D.A., Bergsneider, M. (2013). Redefining the pericontusional penumbra following traumatic brain injury: evidence of deteriorating metabolic derangements based on positron emission tomography. J. Neurotrauma 30, 352-360.
225. Honda, M., Sase, S., Yokota, K., Ichibayashi, R., Yoshihara, K., Masuda, H., Uekusa, H., Nomoto, J., Sugo, N., Kishi, T., Seiki, Y. (2013). Early cerebral circulation disturbance in patients suffering from different types of severe traumatic brain injury: a xenon CT and perfusion CT study. Acta Neurochir. Suppl. 118, 259-263.
226. Liu, W., Wang, B., Wolfowitz, R., Yeh, P.H., Nathan, D.E., Graner, J., Tang, H., Pan, H., Harper, J., Pham, D., Oakes, T.R., French, L.M., Riedy, G. (2013). Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI. NMR Biomed. 26, 651-663.
227. Rangel-Castilla, L., Gasco, J., Nauta, H.J., Okonkwo, D.O., Robertson, C.S. (2008). Cerebral pressure autoregulation in traumatic brain injury. Neurosurg. Focus 25, E7.
228. Oda, Y., Gao, G., Wei, E.P., Povlishock, J.T. (2011). Combinational therapy using hypothermia and the immunophilin ligand FK506 to target altered pial arteriolar reactivity, axonal damage, blood-brain barrier dysfunction after traumatic brain injury in rat. J. Cereb. Blood Flow Metab. 31, 1143-1154.
229. Baranova, A.I., Wei, E.P., Ueda, Y., Sholley, M.M., Kontos, H.A., Povlishock, J.T. (2008). Cerebral vascular responsiveness after experimental traumatic brain injury: the beneficial effects of delayed hypothermia combined with superoxide dismutase administration. J. Neurosurg. 109, 502-509.
230. Danton, G.H., Prado, R., Truettner, J., Watson, B.D., Dietrich, W.D. (2002). Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats. J. Cereb. Blood Flow Metab. 22, 612-619.
231. Wei, E.P., Dietrich, W.D., Povlishock, J.T., Navari, R.M., Kontos, H.A. (1980). Functional, morphological, metabolic abnormalities of the cerebral microcirculation after concussive brain injury in cats. Circ. Res. 46, 37-47.
232. Len, T.K., Neary, J.P., Asmundson, G.J., Candow, D.G., Goodman, D.G., Bjornson, B., Bhambhani, Y.N. (2013). Serial monitoring of CO2 reactivity following sport concussion using hypocapnia and hypercapnia. Brain Inj. 27, 346-353.
233. Bailey, D.M., Jones, D.W., Sinnott, A., Brugniaux, J.V., New, K.J., Hodson, D., Marley, C.J., Smirl, J.D., Ogoh, S., Ainslie, P.N. (2013). Impaired cerebral haemodynamic function associated with chronic traumatic brain injury in professional boxers. Clin. Sci. 124, 177-189.
234. Kim, J., Whyte, J., Patel, S., Europa, E., Slattery, J., Coslett, H.B., Detre, J.A. (2012). A perfusion fMRI study of the neural correlates of sustained-attention and working-memory deficits in chronic traumatic brain injury. Neurorehabil. Neural Repair 26, 870-880.
235. Hayward, N.M., Immonen, R., Tuunanen, P.I., Ndode-Ekane, X.E., Grohn, O., Pitkanen, A. (2010). Association of chronic vascular changes with functional outcome after traumatic brain injury in rats. J. Neurotrauma 27, 2203-2219.
236. Hayward, N.M., Tuunanen, P.I., Immonen, R., Ndode-Ekane, X.E., Pitkanen, A., Grohn, O. (2011). Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats. J. Cereb. Blood Flow Metab. 31, 166-177.
237. Abdel-Dayem, H.M., Abu-Judeh, H., Kumar, M., Atay, S., Naddaf, S., El-Zeftawy, H., Luo, J.Q. (1998). SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury. Clin. Nucl. Med. 23, 309-317.
238. Goldenberg, G., Oder, W., Spatt, J., Podreka, I. (1992). Cerebral correlates of disturbed executive function and memory in survivors of severe closed head injury: a SPECT study. J. Neurol. Neurosurg. Psychiatry 55, 362-368.
239. Gray, B.G., Ichise, M., Chung, D.G., Kirsh, J.C., Franks, W. (1992). Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: a comparison with X-ray computed tomography. J. Nucl. Med. 33, 52-58.
240. Jacobs, A., Put, E., Ingels, M., Put, T., Bossuyt, A. (1996). Oneyear follow-up of technetium-99m-HMPAO SPECT in mild head injury. J. Nucl. Med. 37, 1605-1609.
241. Kochanek, P.M., Hendrich, K.S., Dixon, C.E., Schiding, J.K., Williams, D.S., Ho, C. (2002). Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging. J. Neurotrauma 19, 1029-1037.
242. Stein, S.C., Graham, D.I., Chen, X.H., Smith, D.H. (2004). Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injury. Neurosurgery 54, 687-691; discussion, 691.
243. Stein, S.C., Smith, D.H. (2004). Coagulopathy in traumatic brain injury. Neurocrit. Care 1, 479-488.
244. Daneshvar, D.H., Riley, D.O., Nowinski, C.J., McKee, A.C., Stern, R.A., Cantu, R.C. (2011). Long-term consequences: effects on normal development profile after concussion. Phys. Med. Rehabil. Clin. N. Am. 22, 683-700, ix.
245. Plassman, B.L., Havlik, R.J., Steffens, D.C., Helms, M.J., Newman, T.N., Drosdick, D., Phillips, C., Gau, B.A., Welsh-Bohmer, K.A., Burke, J.R., Guralnik, J.M., Breitner, J.C. (2000). Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 55, 1158-1166.
246. Jellinger, K.A., Paulus, W., Wrocklage, C., Litvan, I. (2001). Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype. BMC Neurol. 1, 3.
247. Blumbergs, P.C., Scott, G., Manavis, J., Wainwright, H., Simpson, D.A., McLean, A.J. (1994). Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344, 1055-1056.
248. Graham, D.I., Gentleman, S.M., Lynch, A., Roberts, G.W. (1995). Distribution of beta-amyloid protein in the brain following severe head injury. Neuropathol. Appl. Neurobiol. 21, 27-34.
249. Lewen, A., Li, G.L., Nilsson, P., Olsson, Y., Hillered, L. (1995). Traumatic brain injury in rat produces changes of beta-amyloid precursor protein immunoreactivity. Neuroreport 6, 357-360.
250. Hamberger, A., Huang, Y.L., Zhu, H., Bao, F., Ding, M., Blennow, K., Olsson, A., Hansson, H.A., Viano, D., Haglid, K.G. (2003). Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head. J. Neurotrauma 20, 169-178.
251. Bramlett, H.M., Dietrich, W.D. (2003). Synuclein aggregation: possible role in traumatic brain injury. Exp. Neurol. 184, 27-30.
252. Irving, E.A., Nicoll, J., Graham, D.I., Dewar, D. (1996). Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neurosci. Lett. 213, 189-192.
253. Sherriff, F.E., Bridges, L.R., Sivaloganathan, S. (1994). Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein. Acta Neuropathol. (Berl.) 87, 55-62.
254. Baugh, C.M., Stamm, J.M., Riley, D.O., Gavett, B.E., Shenton, M.E., Lin, A., Nowinski, C.J., Cantu, R.C., McKee, A.C., Stern, R.A. (2012). Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 6, 244-254.
255. Castillo-Carranza, D.L., Lasagna-Reeves, C.A., Kayed, R. (2013). Tau aggregates as immunotherapeutic targets. Front. Biosci. 5, 426-438.
256. Schenk, D., Basi, G.S., Pangalos, M.N. (2012). Treatment strategies targeting amyloid beta-protein. Cold Spring Harb. Perspect. Med. 2, a006387.
257. Schneeberger, A., Mandler, M., Mattner, F., Schmidt, W. (2012). Vaccination for Parkinson's disease. Parkinsonism Relat. Disord. 18, Suppl. 1, S11-S13.
258. McConeghy, K.W., Hatton, J., Hughes, L., Cook, A.M. (2012). A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury. CNS Drugs 26, 613-636.
259. Steward, O., Popovich, P.G., Dietrich, W.D., Kleitman, N. (2012). Replication and reproducibility in spinal cord injury research. Exp. Neurol. 233, 597-605.
260. Nielson, J.L., Guandique, C.F., Liu, A.W., Burke, D.A., Lash, A.T., Moseanko, R., Hawbecker, S., Strand, S.C., Zdunowski, S., Irvine, K.A., Brock, J.H., Nout-Lomas, Y.S., Gensel, J.C., Anderson, K.D., Segal, M.R., Rosenzweig, E.S., Magnuson, D.S., Whittemore, S.R., McTigue, D.M., Popovich, P.G., Rabchevsky, A.G., Scheff, S.W., Steward, O., Courtine, G., Edgerton, V.R., Tuszynski, M.H., Beattie, M.S., Bresnahan, J.C., Ferguson, A.R. (2014). Development of a database for translational spinal cord injury research. J. Neurotrauma 31, 1789-1799.
261. Kochanek, P.M., Bramlett, H., Dietrich, W.D., Dixon, C.E., Hayes, R.L., Povlishock, J., Tortella, F.C., Wang, K.K. (2011). A novel multicenter preclinical drug screening and biomarker consortium for experimental traumatic brain injury: operation brain trauma therapy. J. Trauma 71, S15-S24.
262. Lemmon, V.P., Ferguson, A.R., Popovich, P.G., Xu, X.M., Snow, D.M., Igarashi, M., Beattie, C.E., Bixby, J.L. (2014). Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments. J. Neurotrauma 31, 1354-1361.