Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes

Journal of Neuroinflammation

Volumn 10, Issue , 2013, Pages

  Ekmark Lewén, Sara ^a   Flygt, Johanna ^a   Kiwanuka, Olivia ^a   Meyerson, Bengt J ^b   Lewén, Anders ^a   Hillered, Lars ^a   Marklund, Niklas ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UPPSALA UNIVERSITY   (Sweden)

Author keywords

amyloid precursor protein ( APP); Astrocytes; Central fluid percussion injury; Diffuse traumatic axonal injury; Functional outcome; Inflammatory response; Mouse

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CD3 ANTIGEN; CELL PROTEIN; GLIAL FIBRILLARY ACIDIC PROTEIN; IMMUNOGLOBULIN G; PROTEIN GR 1; PROTEIN MAC 2; UNCLASSIFIED DRUG; VIMENTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AXONAL INJURY; BEHAVIOR DISORDER; BLOOD BRAIN BARRIER; BRAIN CORTEX; CAPSULA INTERNA; CELL ACTIVATION; CONTROLLED STUDY; EXPLORATORY BEHAVIOR; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MACROGLIA; MALE; MEMBRANE PERMEABILITY; MOUSE; NERVOUS SYSTEM INFLAMMATION; NEUTROPHIL CHEMOTAXIS; NONHUMAN; T LYMPHOCYTE; THALAMUS; WHITE MATTER;

AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ASTROCYTES; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; BRAIN INJURIES; CELL COUNT; DIFFUSE AXONAL INJURY; GLIAL FIBRILLARY ACIDIC PROTEIN; IMMUNOHISTOCHEMISTRY; INFLAMMATION; MALE; MICE; MICE, INBRED C57BL; NEUTROPHIL INFILTRATION; TREATMENT OUTCOME; VIMENTIN;

EID: 84875688606     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/1742-2094-10-44     Document Type: Article

References (90)

1. Gennarelli TA, Thibault LE, Adams JH, Graham DI, Thompson CJ, Marcincin RP. Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 1982, 12:564-574. 10.1002/ana.410120611, 7159060.
2. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 1989, 15:49-59. 10.1111/j.1365-2559.1989.tb03040.x, 2767623.
3. Abou-Hamden A, Blumbergs PC, Scott G, Manavis J, Wainwright H, Jones N, McLean J. Axonal injury in falls. J Neurotrauma 1997, 14:699-713. 10.1089/neu.1997.14.699, 9383089.
4. Pittella JE, Gusmao SN. The conformation of the brain plays an important role in the distribution of diffuse axonal injury in fatal road traffic accident. Arq Neuropsiquiatr 2004, 62:406-412. 10.1590/S0004-282X2004000300007, 15273836.
5. Greer JE, McGinn MJ, Povlishock JT. Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, and axonal outgrowth in the axotomized neuronal population. J Neurosci 2011, 31:5089-5105. 10.1523/JNEUROSCI.5103-10.2011, 3076099, 21451046.
6. Strich S. Diffuse degeneration of the cerebral white matter in severe dementia following head injury. J Neurol Neurosurg Psychiatry 1956, 19:163-185. 10.1136/jnnp.19.3.163, 497203, 13357957.
7. Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil 2005, 20:76-94. 10.1097/00001199-200501000-00008, 15668572.
8. Graham DI, McLellan D, Adams JH, Doyle D, Kerr A, Murray LS. The neuropathology of the vegetative state and severe disability after non-missile head injury. Acta NeurochirSuppl (Wien) 1983, 32:65-67.
9. Adams JH, Jennett B, McLellan DR, Murray LS, Graham DI. The neuropathology of the vegetative state after head injury. J Clin Pathol 1999, 52:804-806. 10.1136/jcp.52.11.804, 501589, 10690167.
10. Lipton ML, Gellella E, Lo C, Gold T, Ardekani BA, Shifteh K, Bello JA, Branch CA. Multifocal white matter ultrastructural abnormalities in mild traumatic brain injury with cognitive disability: a voxel-wise analysis of diffusion tensor imaging. J Neurotrauma 2008, 25:1335-1342. 10.1089/neu.2008.0547, 19061376.
11. Lipton ML, Gulko E, Zimmerman ME, Friedman BW, Kim M, Gellella E, Gold T, Shifteh K, Ardekani BA, Branch CA. Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury. Radiology 2009, 252:816-824. 10.1148/radiol.2523081584, 19567646.
12. Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain 2003, 126:515-530. 10.1093/brain/awg061, 12566274.
13. Huebner EA, Strittmatter SM. Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ 2009, 48:339-351. 2846285, 19582408.
14. Vink R, Van Den Heuvel C. Recent advances in the development of multifactorial therapies for the treatment of traumatic brain injury. Expert Opin Investig Drugs 2004, 13:1263-1274. 10.1517/13543784.13.10.1263, 15461556.
15. Marklund N, Bakshi A, Castelbuono D, McIntosh T. Evaluation of pharmacological treatment strategies in traumatic brain injury. Curr Pharm Des 2006, 12(13):1645-1680. 10.2174/138161206776843340, 16729876.
16. Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW. ß-Amyloid precursor protein (β-APP) as a marker for axonal injury after head injury. Neurosci Lett 1993, 160:139-144. 10.1016/0304-3940(93)90398-5, 8247344.
17. Sherriff FE, Bridges LR, Sivaloganathan S. Early detection of axonal injury after human head trauma using immunocytochemistry for beta-amyloid precursor protein. Acta Neuropathol 1994, 87:55-62. 10.1007/BF00386254, 8140894.
18. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA. Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 1995, 12:565-572. 10.1089/neu.1995.12.565, 8683607.
19. McKenzie KJ, McLellan DR, Gentleman SM, Maxwell WL, Gennarelli TA, Graham DI. Is beta-APP a marker of axonal damage in short-surviving head injury?. Acta Neuropathol 1996, 92:608-613. 10.1007/s004010050568, 8960319.
20. Geddes JF, Vowles GH, Beer TW, Ellison DW. The diagnosis of diffuse axonal injury: implications for forensic practice. Neuropathol Appl Neurobiol 1997, 23:339-347. 10.1111/j.1365-2990.1997.tb01305.x, 9292874.
21. Lewen A, Li GL, Nilsson P, Olsson Y, Hillered L. Traumatic brain injury in rat produces changes of beta-amyloid precursor protein immunoreactivity. Neuroreport 1995, 6:357-360. 10.1097/00001756-199501000-00032, 7756628.
22. Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol 2012, Epub ahead of print.
23. Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL. A fluid percussion model of experimental brain injury in the rat. J Neurosurg 1987, 67:110-119. 10.3171/jns.1987.67.1.0110, 3598659.
24. Marmarou A, Foda MA, van den Brink W, Campbell JHK, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 1994, 80(2):291-300. 10.3171/jns.1994.80.2.0291, 8283269.
25. Kelley BJ, Lifshitz J, Povlishock JT. Neuroinflammatory responses after experimental diffuse traumatic brain injury. J Neuropathol Exp Neurol 2007, 66:989-1001. 10.1097/NEN.0b013e3181588245, 17984681.
26. Venkatesan C, Chrzaszcz M, Choi N, Wainwright MS. Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following diffuse axonal injury. J Neuroinflammation 2010, 7:32. 10.1186/1742-2094-7-32, 2891720, 20507613.
27. Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 1991, 39:253-262. 10.1016/0165-0270(91)90104-8, 1787745.
28. Ekmark-Lewen S, Lewen A, Meyerson BJ, Hillered L. The multivariate concentric square field test reveals behavioral profiles of risk taking, exploration, and cognitive impairment in mice subjected to traumatic brain injury. J Neurotrauma 2010, 27:1643-1655. 10.1089/neu.2009.0953, 20578827.
29. Thompson HJ, Lifshitz J, Marklund N, Grady MS, Graham DI, Hovda DA, McIntosh TK. Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma 2005, 22:42-75. 10.1089/neu.2005.22.42, 15665602.
30. Marklund N, Bareyre FM, Royo NC, Thompson HJ, Mir AK, Grady MS, Schwab ME, McIntosh TK. Cognitive outcome following brain injury and treatment with an inhibitor of Nogo-A in association with an attenuated downregulation of hippocampal growth-associated protein-43 expression. J Neurosurg 2007, 107:844-853. 10.3171/JNS-07/10/0844, 2366808, 17937233.
31. PaxinosGaF KBJ. The Mouse Brain in Stereotaxic Coordinates 2001, New York: Academic Press, 2.
32. Eriksson LJE, Kettaneh-Wold N, Trygg J, Wikström C, Wold S. Multi- and megavariate data analysis. Part I: basic principles and applications.Umeå 2006, Sweden: Umetrics AB.
33. Eriksson L, Antti H, Gottfries J, Holmes E, Johansson E, Lindgren F, Long I, Lundstedt T, Trygg J, Wold S. Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm). Anal Bioanal Chem 2004, 380:419-429. 10.1007/s00216-004-2783-y, 15448969.
34. Eriksson L, Andersson PL, Johansson E, Tysklind M. Megavariate analysis of environmental QSAR data. Part II-investigating very complex problem formulations using hierarchical, non-linear and batch-wise extensions of PCA and PLS. Mol Divers 2006, 10:187-205. 10.1007/s11030-006-9026-4, 16802062.
35. Lewen A, Fredriksson A, Li GL, Olsson Y, Hillered L. Behavioural and morphological outcome of mild cortical contusion trauma of the rat brain: influence of NMDA-receptor blockade. Acta Neurochir (Wien) 1999, 141:193-202.
36. Cole JT, Yarnell A, Kean WS, Gold E, Lewis B, Ren M, McMullen DC, Jacobowitz DM, Pollard HB, O'Neill JT, Grunberg NE, Dalgard CL, Frank JA, Watson WD. Craniotomy: true sham for traumatic brain injury, or a sham of a sham?. J Neurotrauma 2011, 28:359-369. 10.1089/neu.2010.1427, 3057208, 21190398.
37. Stone JR, Singleton RH, Povlishock JT. Intra-axonal neurofilament compaction does not evoke local axonal swelling in all traumatically injured axons. Exp Neurol 2001, 172:320-331. 10.1006/exnr.2001.7818, 11716556.
38. Hamm RJ, Pike BR, Temple MD, O'Dell DM, Lyeth BG. The effect of postinjury kindled seizures on cognitive performance of traumatically brain-injured rats. Exp Neurol 1995, 136:143-148. 10.1006/exnr.1995.1091, 7498404.
39. Bolkvadze T, Pitkanen A. Development of post-traumatic epilepsy after controlled cortical impact and lateral fluid-percussion-induced brain injury in the mouse. J Neurotrauma 2012, 29:789-812. 10.1089/neu.2011.1954, 22023672.
40. Golarai G, Greenwood AC, Feeney DM, Connor JA. Physiological and structural evidence for hippocampal involvement in persistent seizure susceptibility after traumatic brain injury. J Neurosci 2001, 21:8523-8537.
41. Nilsson P, Ronne-Engstrom E, Flink R, Ungerstedt U, Carlson H, Hillered L. Epileptic seizure activity in the acute phase following cortical impact trauma in rat. Brain Res 1994, 637:227-232. 10.1016/0006-8993(94)91237-8, 8180800.
42. Rogatsky GG, Sonn J, Kamenir Y, Zarchin N, Mayevsky A. Relationship between intracranial pressure and cortical spreading depression following fluid percussion brain injury in rats. J Neurotrauma 2003, 20:1315-1325. 10.1089/089771503322686111, 14748980.
43. Kharatishvili I, Pitkanen A. Association of the severity of cortical damage with the occurrence of spontaneous seizures and hyperexcitability in an animal model of posttraumatic epilepsy. Epilepsy Res 2010, 90(1-2):47-59.
44. Reeves TM, Lyeth BG, Povlishock JT. Long-term potentiation deficits and excitability changes following traumatic brain injury. Exp Brain Res 1995, 106:248-256.
45. Nilsson B, Ponten U, Voigt G. Experimental head injury in the rat. Part 1: Mechanics, pathophysiology, and morphology in an impact acceleration trauma model. J Neurosurg 1977, 47:241-251. 10.3171/jns.1977.47.2.0241, 874547.
46. Smith DH, Nonaka M, Miller R, Leoni M, Chen XH, Alsop D, Meaney DF. Immediate coma following inertial brain injury dependent on axonal damage in the brainstem. J Neurosurg 2000, 93:315-322. 10.3171/jns.2000.93.2.0315, 10930019.
47. Singleton RH, Zhu J, Stone JR, Povlishock JT. Traumatically induced axotomy adjacent to the soma does not result in acute neuronal death. J Neurosci 2002, 22:791-802.
48. Kelley BJ, Farkas O, Lifshitz J, Povlishock JT. Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration. Exp Neurol 2006, 198:350-360. 10.1016/j.expneurol.2005.12.017, 16448652.
49. Lifshitz J, Kelley BJ, Povlishock JT. Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. J Neuropathol Exp Neurol 2007, 66:218-229. 10.1097/01.jnen.0000248558.75950.4d, 17356383.
50. Uryu K, Chen XH, Martinez D, Browne KD, Johnson VE, Graham DI, Lee VM, Trojanowski JQ, Smith DH. Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol 2007, 208:185-192. 10.1016/j.expneurol.2007.06.018, 17826768.
51. Chen XH, Johnson VE, Uryu K, Trojanowski JQ, Smith DH. A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injury. Brain Pathol 2009, 19:214-223. 10.1111/j.1750-3639.2008.00176.x, 3014260, 18492093.
52. Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease?. Nat Rev Neurosci 2010, 11:361-370.
53. Li Y, Zhang L, Kallakuri S, Zhou R, Cavanaugh JM. Quantitative relationship between axonal injury and mechanical response in a rodent head impact acceleration model. J Neurotrauma 2011, 28:1767-1782. 10.1089/neu.2010.1687, 3172873, 21895482.
54. Bramlett HM, Kraydieh S, Green EJ, Dietrich WD. Temporal and regional patterns of axonal damage following traumatic brain injury: a beta-amyloid precursor protein immunocytochemical study in rats. J Neuropathol Exp Neurol 1997, 56(10):1132-1141. 10.1097/00005072-199710000-00007, 9329457.
55. Pierce JE, Trojanowski JQ, Graham DI, Smith DH, McIntosh TK. Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat. J Neurosci 1996, 16(3):1083-1090.
56. Rafols JA, Morgan R, Kallakuri S, Kreipke CW. Extent of nerve cell injury in Marmarou's model compared to other brain trauma models. Neurol Res 2007, 29:348-355. 10.1179/016164107X204657, 17626729.
57. Kimelberg HK, Norenberg MD. Astrocytic Responses to Central Nervous System Trauma. The Neurobiology of Central Nervous System Trauma 1994, 193-208. New York: Oxford University Press, Salzman SK, Faden AI.
58. Norenberg MD. Astrocyte response to CNS Injury. J Neuropath ExpNeur 1994, 53:213-220.
59. Stichel CC, Muller HW. The CNS lesion scar: new vistas on an old regeneration barrier. Cell Tissue Res 1998, 294:1-9. 10.1007/s004410051151, 9724451.
60. Bignami A. Glial cells in the central nervous system. Discussions in Neuroscience 1991, 111:9-44.
61. Calvo JL, Carbonell AL, Boya J. Co-expression of glial fibrillary acidic protein and vimentin in reactive astrocytes following brain injury in rats. Brain Res 1991, 566:333-336. 10.1016/0006-8993(91)91720-L, 1814551.
62. Schiffer D, Giordana MT, Migheli A, Giaccone G, Pezzotta S, Mauro A. Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain. Brain Res 1986, 374:110-118. 10.1016/0006-8993(86)90399-9, 2424556.
63. Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 2006, 129:2761-2772. 10.1093/brain/awl165, 16825202.
64. Ridet JL, Malhotra SK, Privat A, Gage FH. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 1997, 20:570-577. 10.1016/S0166-2236(97)01139-9, 9416670.
65. Pixley SK, de Vellis J. Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Res 1984, 317:201-209.
66. Ekmark-Lewen S, Lewen A, Israelsson C, Li GL, Farooque M, Olsson Y, Ebendal T, Hillered L. Vimentin and GFAP responses in astrocytes after contusion trauma to the murine brain. Restor Neurol Neurosci 2010, 28:311-321.
67. Pekny M, Eliasson C, Siushansian R, Ding M, Dixon SJ, Pekna M, Wilson JX, Hamberger A. The impact of genetic removal of GFAP and/or vimentin on glutamine levels and transport of glucose and ascorbate in astrocytes. Neurochem Res 1999, 24:1357-1362. 10.1023/A:1022572304626, 10555775.
68. Morganti-Kossmann MC, Satgunaseelan L, Bye N, Kossmann T. Modulation of immune response by head injury. Injury 2007, 38:1392-1400. 10.1016/j.injury.2007.10.005, 18048036.
69. Israelsson C, Bengtsson H, Kylberg A, Kullander K, Lewen A, Hillered L, Ebendal T. Distinct cellular patterns of upregulated chemokine expression supporting a prominent inflammatory role in traumatic brain injury. J Neurotrauma 2008, 25:959-974. 10.1089/neu.2008.0562, 18665806.
70. Israelsson C, Bengtsson H, Lobell A, Nilsson LN, Kylberg A, Isaksson M, Wootz H, Lannfelt L, Kullander K, Hillered L, Ebendal T. Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders. Eur J Neurosci 2010, 31:852-863. 10.1111/j.1460-9568.2010.07105.x, 20374285.
71. Clausen F, Lorant T, Lewen A, Hillered L. T lymphocyte trafficking: a novel target for neuroprotection in traumatic brain injury. J Neurotrauma 2007, 24:1295-1307. 10.1089/neu.2006.0258, 17711391.
72. Clausen F, Hanell A, Israelsson C, Hedin J, Ebendal T, Mir AK, Gram H, Marklund N. Neutralization of interleukin-1beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice. Eur J Neurosci 2011, 34:110-123. 10.1111/j.1460-9568.2011.07723.x, 21623956.
73. Lloyd E, Somera-Molina K, Van Eldik LJ, Watterson DM, Wainwright MS. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury. J Neuroinflammation 2008, 5:28. 10.1186/1742-2094-5-28, 2483713, 18590543.
74. Yatsiv I, Grigoriadis N, Simeonidou C, Stahel PF, Schmidt OI, Alexandrovitch AG, Tsenter J, Shohami E. Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury. FASEB J 2005, 19:1701-1703.
75. Bye N, Habgood MD, Callaway JK, Malakooti N, Potter A, Kossmann T, Morganti-Kossmann MC. Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration. Exp Neurol 2007, 204:220-233. 10.1016/j.expneurol.2006.10.013, 17188268.
76. Helmy A, Carpenter KL, Menon DK, Pickard JD, Hutchinson PJ. The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production. J Cereb Blood Flow Metab 2011, 31:658-670. 10.1038/jcbfm.2010.142, 3049520, 20717122.
77. Helmy A, De Simoni MG, Guilfoyle MR, Carpenter KL, Hutchinson PJ. Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog Neurobiol 2011, 95:352-372. 10.1016/j.pneurobio.2011.09.003, 21939729.
78. Giulian D, Baker TJ, Shih LC, Lachman LB. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med 1986, 164:594-604. 10.1084/jem.164.2.594, 2188228, 3487617.
79. Pearson VL, Rothwell NJ, Toulmond S. Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death. Glia 1999, 25:311-323. 10.1002/(SICI)1098-1136(19990215)25:4<311::AID-GLIA1>3.0.CO;2-E, 10028914.
80. Clausen F, Hanell A, Bjork M, Hillered L, Mir AK, Gram H, Marklund N. Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice. Eur J Neurosci 2009, 30:385-396. 10.1111/j.1460-9568.2009.06820.x, 19614750.
81. Rivest S. Regulation of innate immune responses in the brain. Nat Rev Immunol 2009, 9:429-439. 10.1038/nri2565, 19461673.
82. Holmin S, Soderlund J, Biberfeld P, Mathiesen T. Intracerebral inflammation after human brain contusion. Neurosurgery 1998, 42:291-298. Discussion 298-299, 10.1097/00006123-199802000-00047, 9482179.
83. Wedmore CV, Williams TJ. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature 1981, 289:646-650. 10.1038/289646a0, 7464931.
84. Lindbom L. Regulation of vascular permeability by neutrophils in acute inflammation. Chem Immunol Allergy 2003, 83:146-166.
85. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010, 87:779-789. 10.1189/jlb.1109766, 2858674, 20130219.
86. Kenne E, Erlandsson A, Lindbom L, Hillered L, Clausen F. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice. J Neuroinflammation 2012, 9:17. 10.1186/1742-2094-9-17, 3292978, 22269349.
87. Holmin S, Mathiesen T, Shetye J, Biberfeld P. Intracerebral inflammatory response to experimental brain contusion. Acta Neurochir (Wien) 1995, 132(1-3):110-119.
88. Roman E, Gustafsson L, Berg M, Nylander I. Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation. Horm Behav 2006, 50:736-747. 10.1016/j.yhbeh.2006.06.016, 16876800.
89. Meyerson BJ, Augustsson H, Berg M, Roman E. The Concentric Square Field: a multivariate test arena for analysis of explorative strategies. Behav Brain Res 2006, 168:100-113. 10.1016/j.bbr.2005.10.020, 16356558.
90. Maruichi K, Kuroda S, Chiba Y, Hokari M, Shichinohe H, Hida K, Iwasaki Y. Transplanted bone marrow stromal cells improves cognitive dysfunction due to diffuse axonal injury in rats. Neuropathology 2009, 29:422-432. 10.1111/j.1440-1789.2008.00995.x, 19170895.