Cerebral Edema in Traumatic Brain Injury: Pathophysiology and Prospective Therapeutic Targets

Neurosurgery Clinics of North America

Volumn 27, Issue 4, 2016, Pages 473-488

  Winkler, Ethan A ^a,b   Minter, Daniel ^b   Yue, John K ^a,b   Manley, Geoffrey T ^a,b  

^a SAN FRANCISCO GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Blood brain barrier; Cerebral edema; Pathophysiology; Therapeutic targets; Traumatic brain injury

Indexed keywords

1 (5 IODO 1 NAPHTHALENESULFONYL)HEXAHYDRO 1H 1,4 DIAZEPINE; 2 [[(4 PHENOXYPHENYL)SULFONYL]METHYL]THIIRANE; AQUAPORIN; ARGIPRESSIN; BORTEZOMIB; BUMETANIDE; DEXAMETHASONE; GLIBENCLAMIDE; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; MATRIX METALLOPROTEINASE; METHYLPREDNISOLONE; MYOSIN LIGHT CHAIN KINASE; N ACETYLTRYPTOPHAN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PIOGLITAZONE; RELCOVAPTAN; ROSIGLITAZONE; SODIUM POTASSIUM CHLORIDE COTRANSPORTER 1; SUBSTANCE P; SULFONYLUREA RECEPTOR 1; VASCULOTROPIN;

BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; BRAIN CONTUSION; BRAIN EDEMA; BRAIN ISCHEMIA; COGNITIVE DEFECT; CYTOTOXIC EDEMA; DRUG MECHANISM; DRUG MEGADOSE; DRUG TARGETING; HUMAN; INJURY SEVERITY; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SUBARACHNOID HEMORRHAGE; TRAUMATIC BRAIN INJURY; VASOGENIC EDEMA; BRAIN; BRAIN INJURIES, TRAUMATIC; COMPLICATION;

BLOOD-BRAIN BARRIER; BRAIN; BRAIN EDEMA; BRAIN INJURIES, TRAUMATIC; HUMANS;

EID: 84990902997     PISSN: 10423680     EISSN: 15581349     Source Type: Journal    
DOI: 10.1016/j.nec.2016.05.008     Document Type: Review

References (143)

1. 1 Manley, G.T., Maas, A.I., Traumatic brain injury: an international knowledge-based approach. JAMA 310 (2013), 473–474.
2. 2 Menon, D.K., Schwab, K., Wright, D.W., et al. Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil 91 (2010), 1637–1640.
3. 3 Faul, M., Xu, L., Wald, M.M., et al. Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths, 2002-2006. 2010, Centers for Disease Control and Prevention, National Center for Injury, Atlanta (GA).
4. 4 Langlois, J.A., Rutland-Brown, W., Wald, M.M., The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21 (2006), 375–378.
5. 5 Maas, A.I., Stocchetti, N., Bullock, R., Moderate and severe traumatic brain injury in adults. Lancet Neurol 7 (2008), 728–741.
6. 6 Rosenfeld, J.V., Maas, A.I., Bragge, P., et al. Early management of severe traumatic brain injury. Lancet 380 (2012), 1088–1098.
7. 7 Masel, B.E., DeWitt, D.S., Traumatic brain injury: a disease process, not an event. J Neurotrauma 27 (2010), 1529–1540.
8. 8 Xiong, Y., Mahmood, A., Chopp, M., Animal models of traumatic brain injury. Nat Rev Neurosci 14 (2013), 128–142.
9. 9 Stocchetti, N., Maas, A.I., Traumatic intracranial hypertension. N Engl J Med 370 (2014), 2121–2130.
10. 10 Kim, D.J., Czosnyka, Z., Kasprowicz, M., et al. Continuous monitoring of the Monro-Kellie doctrine: is it possible?. J Neurotrauma 29 (2012), 1354–1363.
11. 11 Sheth, K.N., Stein, D.M., Aarabi, B., et al. Intracranial pressure dose and outcome in traumatic brain injury. Neurocrit Care 18 (2013), 26–32.
12. 12 Stocchetti, N., Maas, A.I., Traumatic intracranial hypertension. N Engl J Med, 371, 2014, 972.
13. 13 Klatzo, I., Pathophysiological aspects of brain edema. Acta Neuropathol 72 (1987), 236–239.
14. 14 Marmarou, A., A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus, 22, 2007, E1.
15. 15 Thal, S.C., Neuhaus, W., The blood-brain barrier as a target in traumatic brain injury treatment. Arch Med Res 45 (2014), 698–710.
16. 16 Rungta, R.L., Choi, H.B., Tyson, J.R., et al. The cellular mechanisms of neuronal swelling underlying cytotoxic edema. Cell 161 (2015), 610–621.
17. 17 Thrane, A.S., Rappold, P.M., Fujita, T., et al. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A 108 (2011), 846–851.
18. 18 Beaumont, A., Fatouros, P., Gennarelli, T., et al. Bolus tracer delivery measured by MRI confirms edema without blood-brain barrier permeability in diffuse traumatic brain injury. Acta Neurochir Suppl 96 (2006), 171–174.
19. 19 Marmarou, A., Pathophysiology of traumatic brain edema: current concepts. Acta Neurochir Suppl 86 (2003), 7–10.
20. 20 Marmarou, A., Signoretti, S., Fatouros, P.P., et al. Predominance of cellular edema in traumatic brain swelling in patients with severe head injuries. J Neurosurg 104 (2006), 720–730.
21. 21 Hudak, A.M., Peng, L., Marquez de la Plata, C., et al. Cytotoxic and vasogenic cerebral oedema in traumatic brain injury: assessment with FLAIR and DWI imaging. Brain Inj 28 (2014), 1602–1609.
22. 22 Beaumont, A., Marmarou, A., Hayasaki, K., et al. The permissive nature of blood brain barrier (BBB) opening in edema formation following traumatic brain injury. Acta Neurochir Suppl 76 (2000), 125–129.
23. 23 Stocchetti, N., Colombo, A., Ortolano, F., et al. Time course of intracranial hypertension after traumatic brain injury. J Neurotrauma 24 (2007), 1339–1346.
24. 24 Winkler, E.A., Bell, R.D., Zlokovic, B.V., Central nervous system pericytes in health and disease. Nat Neurosci 14 (2011), 1398–1405.
25. 25 Zlokovic, B.V., The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57 (2008), 178–201.
26. 26 Winkler, E.A., Sengillo, J.D., Bell, R.D., et al. Blood-spinal cord barrier pericyte reductions contribute to increased capillary permeability. J Cereb Blood Flow Metab 32 (2012), 1841–1852.
27. 27 Winkler, E.A., Sagare, A.P., Zlokovic, B.V., The pericyte: a forgotten cell type with important implications for Alzheimer's disease?. Brain Pathol 24 (2014), 371–386.
28. 28 Zlokovic, B.V., Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 12 (2011), 723–738.
29. 29 Bell, R.D., Winkler, E.A., Sagare, A.P., et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68 (2010), 409–427.
30. 30 Abbott, N.J., Ronnback, L., Hansson, E., Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7 (2006), 41–53.
31. 31 Iliff, J.J., Wang, M., Liao, Y., et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med, 4, 2012, 147ra111.
32. 32 Manley, G.T., Fujimura, M., Ma, T., et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6 (2000), 159–163.
33. 33 Chodobski, A., Zink, B.J., Szmydynger-Chodobska, J., Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res 2 (2011), 492–516.
34. 34 Dore-Duffy, P., Owen, C., Balabanov, R., et al. Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc Res 60 (2000), 55–69.
35. 35 Zehendner, C.M., Sebastiani, A., Hugonnet, A., et al. Traumatic brain injury results in rapid pericyte loss followed by reactive pericytosis in the cerebral cortex. Sci Rep, 5, 2015, 13497.
36. 36 Readnower, R.D., Chavko, M., Adeeb, S., et al. Increase in blood-brain barrier permeability, oxidative stress, and activated microglia in a rat model of blast-induced traumatic brain injury. J Neurosci Res 88 (2010), 3530–3539.
37. 37 Tanno, H., Nockels, R.P., Pitts, L.H., et al. Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: distribution and time course of protein extravasation. J Neurotrauma 9 (1992), 21–32.
38. 38 Shetty, A.K., Mishra, V., Kodali, M., et al. Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves. Front Cell Neurosci, 8, 2014, 232.
39. 39 Yeoh, S., Bell, E.D., Monson, K.L., Distribution of blood-brain barrier disruption in primary blast injury. Ann Biomed Eng 41 (2013), 2206–2214.
40. 40 Abdul-Muneer, P.M., Schuetz, H., Wang, F., et al. Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast. Free Radic Biol Med 60 (2013), 282–291.
41. 41 Elder, G.A., Gama Sosa, M.A., De Gasperi, R., et al. Vascular and inflammatory factors in the pathophysiology of blast-induced brain injury. Front Neurol, 6, 2015, 48.
42. 42 Gama Sosa, M.A., De Gasperi, R., Janssen, P.L., et al. Selective vulnerability of the cerebral vasculature to blast injury in a rat model of mild traumatic brain injury. Acta Neuropathol Commun, 2, 2014, 67.
43. 43 Tang, X., Zhong, W., Tu, Q., et al. NADPH oxidase mediates the expression of MMP-9 in cerebral tissue after ischemia-reperfusion damage. Neurol Res 36 (2014), 118–125.
44. 44 Alves, J.L., Blood-brain barrier and traumatic brain injury. J Neurosci Res 92 (2014), 141–147.
45. 45 Brown, G.C., Neher, J.J., Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol 41 (2010), 242–247.
46. 46 Bolton, S.J., Anthony, D.C., Perry, V.H., Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86 (1998), 1245–1257.
47. 47 Rosenberg, G.A., Yang, Y., Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia. Neurosurg Focus, 22, 2007, E4.
48. 48 Walker, K., Perkins, M., Dray, A., Kinins and kinin receptors in the nervous system. Neurochem Int 26 (1995), 1–16 [discussion: 17–26].
49. 49 Szmydynger-Chodobska, J., Fox, L.M., Lynch, K.M., et al. Vasopressin amplifies the production of proinflammatory mediators in traumatic brain injury. J Neurotrauma 27 (2010), 1449–1461.
50. 50 Winkler, E.A., Sengillo, J.D., Sagare, A.P., et al. Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci U S A 111 (2014), E1035–E1042.
51. 51 Seiffert, E., Dreier, J.P., Ivens, S., et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci 24 (2004), 7829–7836.
52. 52 Mori, K., Miyazaki, M., Iwase, H., et al. Temporal profile of changes in brain tissue extracellular space and extracellular ion (Na(+), K(+)) concentrations after cerebral ischemia and the effects of mild cerebral hypothermia. J Neurotrauma 19 (2002), 1261–1270.
53. 53 Stiefel, M.F., Tomita, Y., Marmarou, A., Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury. J Neurosurg 103 (2005), 707–714.
54. 54 Chen, M., Simard, J.M., Cell swelling and a nonselective cation channel regulated by internal Ca2+ and ATP in native reactive astrocytes from adult rat brain. J Neurosci 21 (2001), 6512–6521.
55. 55 Jayakumar, A.R., Panickar, K.S., Curtis, K.M., et al. Na-K-Cl cotransporter-1 in the mechanism of cell swelling in cultured astrocytes after fluid percussion injury. J Neurochem 117 (2011), 437–448.
56. 56 Lu, K.T., Wu, C.Y., Cheng, N.C., et al. Inhibition of the Na+ -K+ -2Cl- -cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage. Eur J Pharmacol 548 (2006), 99–105.
57. 57 Shohami, E., Biegon, A., Novel approach to the role of NMDA receptors in traumatic brain injury. CNS Neurol Disord Drug Targets 13 (2014), 567–573.
58. 58 Simard, J.M., Woo, S.K., Schwartzbauer, G.T., et al. Sulfonylurea receptor 1 in central nervous system injury: a focused review. J Cereb Blood Flow Metab 32 (2012), 1699–1717.
59. 59 Kahle, K.T., Simard, J.M., Staley, K.J., et al. Molecular mechanisms of ischemic cerebral edema: role of electroneutral ion transport. Physiology (Bethesda) 24 (2009), 257–265.
60. 60 Simard, J.M., Kahle, K.T., Gerzanich, V., Molecular mechanisms of microvascular failure in central nervous system injury–synergistic roles of NKCC1 and SUR1/TRPM4. J Neurosurg 113 (2010), 622–629.
61. 61 Verkman, A.S., Anderson, M.O., Papadopoulos, M.C., Aquaporins: important but elusive drug targets. Nat Rev Drug Discov 13 (2014), 259–277.
62. 62 Verkman, A.S., Yang, B., Song, Y., et al. Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol 85:Spec No (2000), 233S–241S.
63. 63 Zador, Z., Bloch, O., Yao, X., et al. Aquaporins: role in cerebral edema and brain water balance. Prog Brain Res 161 (2007), 185–194.
64. 64 Oshio, K., Song, Y., Verkman, A.S., et al. Aquaporin-1 deletion reduces osmotic water permeability and cerebrospinal fluid production. Acta Neurochir Suppl 86 (2003), 525–528.
65. 65 Bloch, O., Manley, G.T., The role of aquaporin-4 in cerebral water transport and edema. Neurosurg Focus, 22, 2007, E3.
66. 66 Nagelhus, E.A., Mathiisen, T.M., Ottersen, O.P., Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 129 (2004), 905–913.
67. 67 Solenov, E., Watanabe, H., Manley, G.T., et al. Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method. Am J Physiol Cell Physiol 286 (2004), C426–C432.
68. 68 Ishmael, J.E., Lohr, C.V., Fischer, K., et al. Localization of myosin II regulatory light chain in the cerebral vasculature. Acta Histochem 110 (2008), 172–177.
69. 69 Shen, Q., Rigor, R.R., Pivetti, C.D., et al. Myosin light chain kinase in microvascular endothelial barrier function. Cardiovasc Res 87 (2010), 272–280.
70. 70 Luh, C., Kuhlmann, C.R., Ackermann, B., et al. Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury. J Neurochem 112 (2010), 1015–1025.
71. 71 Rossi, J.L., Todd, T., Bazan, N.G., et al. Inhibition of myosin light-chain kinase attenuates cerebral edema after traumatic brain injury in postnatal mice. J Neurotrauma 30 (2013), 1672–1679.
72. 72 Haorah, J., Heilman, D., Knipe, B., et al. Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise. Alcohol Clin Exp Res 29 (2005), 999–1009.
73. 73 Kuhlmann, C.R., Tamaki, R., Gamerdinger, M., et al. Inhibition of the myosin light chain kinase prevents hypoxia-induced blood-brain barrier disruption. J Neurochem 102 (2007), 501–507.
74. 74 Ramirez, S.H., Potula, R., Fan, S., et al. Methamphetamine disrupts blood-brain barrier function by induction of oxidative stress in brain endothelial cells. J Cereb Blood Flow Metab 29 (2009), 1933–1945.
75. 75 Filippini, G., Brusaferri, F., Sibley, W.A., et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev(4), 2000 CD001331.
76. 76 Ryken, T.C., McDermott, M., Robinson, P.D., et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96 (2010), 103–114.
77. 77 Salvador, E., Shityakov, S., Forster, C., Glucocorticoids and endothelial cell barrier function. Cell Tissue Res 355 (2014), 597–605.
78. 78 Alderson, P., Roberts, I., Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev(1), 2005 CD000196.
79. 79 Sandercock, P.A., Soane, T., Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev(9), 2011 CD000064.
80. 80 Bratton, S.L., Chestnut, R.M., Ghajar, J., et al. Guidelines for the management of severe traumatic brain injury. XV. Steroids. J Neurotrauma 24:Suppl 1 (2007), S91–S95.
81. 81 Thal, S.C., Schaible, E.V., Neuhaus, W., et al. Inhibition of proteasomal glucocorticoid receptor degradation restores dexamethasone-mediated stabilization of the blood-brain barrier after traumatic brain injury. Crit Care Med 41 (2013), 1305–1315.
82. 82 Kleinschnitz, C., Blecharz, K., Kahles, T., et al. Glucocorticoid insensitivity at the hypoxic blood-brain barrier can be reversed by inhibition of the proteasome. Stroke 42 (2011), 1081–1089.
83. 83 Stahel, P.F., Smith, W.R., Bruchis, J., et al. Peroxisome proliferator-activated receptors: “key” regulators of neuroinflammation after traumatic brain injury. PPAR Res, 2008, 2008, 538141.
84. 84 Moreno, S., Farioli-Vecchioli, S., Ceru, M.P., Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123 (2004), 131–145.
85. 85 Besson, V.C., Chen, X.R., Plotkine, M., et al. Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, exerts neuroprotective effects in traumatic brain injury. Neurosci Lett 388 (2005), 7–12.
86. 86 Chen, X.R., Besson, V.C., Palmier, B., et al. Neurological recovery-promoting, anti-inflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury. J Neurotrauma 24 (2007), 1119–1131.
87. 87 Mysiorek, C., Culot, M., Dehouck, L., et al. Peroxisome-proliferator-activated receptor-alpha activation protects brain capillary endothelial cells from oxygen-glucose deprivation-induced hyperpermeability in the blood-brain barrier. Curr Neurovasc Res 6 (2009), 181–193.
88. 88 Sauerbeck, A., Gao, J., Readnower, R., et al. Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Exp Neurol 227 (2011), 128–135.
89. 89 Yi, J.H., Park, S.W., Brooks, N., et al. PPARgamma agonist rosiglitazone is neuroprotective after traumatic brain injury via anti-inflammatory and anti-oxidative mechanisms. Brain Res 1244 (2008), 164–172.
90. 90 Zhu, D., Wang, Y., Singh, I., et al. Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115 (2010), 4963–4972.
91. 91 Nag, S., Manias, J.L., Stewart, D.J., Pathology and new players in the pathogenesis of brain edema. Acta Neuropathol 118 (2009), 197–217.
92. 92 Storkebaum, E., Quaegebeur, A., Vikkula, M., et al. Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nat Neurosci 14 (2011), 1390–1397.
93. 93 Carmeliet, P., Jain, R.K., Molecular mechanisms and clinical applications of angiogenesis. Nature 473 (2011), 298–307.
94. 94 Dore-Duffy, P., Wang, X., Mehedi, A., et al. Differential expression of capillary VEGF isoforms following traumatic brain injury. Neurol Res 29 (2007), 395–403.
95. 95 Shore, P.M., Jackson, E.K., Wisniewski, S.R., et al. Vascular endothelial growth factor is increased in cerebrospinal fluid after traumatic brain injury in infants and children. Neurosurgery 54 (2004), 605–611 [discussion: 611–2].
96. 96 Chodobski, A., Chung, I., Kozniewska, E., et al. Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injury. Neuroscience 122 (2003), 853–867.
97. 97 Hirose, T., Matsumoto, N., Tasaki, O., et al. Delayed progression of edema formation around a hematoma expressing high levels of VEGF and mmp-9 in a patient with traumatic brain injury: case report. Neurol Med Chir (Tokyo) 53 (2013), 609–612.
98. 98 Koyama, J., Miyake, S., Sasayama, T., et al. Effect of VEGF receptor antagonist (VGA1155) on brain edema in the rat cold injury model. Kobe J Med Sci 53 (2007), 199–207.
99. 99 Kimura, R., Nakase, H., Tamaki, R., et al. Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction. Stroke 36 (2005), 1259–1263.
100. 100 van Bruggen, N., Thibodeaux, H., Palmer, J.T., et al. VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104 (1999), 1613–1620.
101. 101 Thau-Zuchman, O., Shohami, E., Alexandrovich, A.G., et al. Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. J Cereb Blood Flow Metab 30 (2010), 1008–1016.
102. 102 Nag, S., Kapadia, A., Stewart, D.J., Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 37 (2011), 3–23.
103. 103 Rosenberg, G.A., Matrix metalloproteinases in neuroinflammation. Glia 39 (2002), 279–291.
104. 104 Bell, R.D., Winkler, E.A., Singh, I., et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485 (2012), 512–516.
105. 105 Grossetete, M., Phelps, J., Arko, L., et al. Elevation of matrix metalloproteinases 3 and 9 in cerebrospinal fluid and blood in patients with severe traumatic brain injury. Neurosurgery 65 (2009), 702–708.
106. 106 Hadass, O., Tomlinson, B.N., Gooyit, M., et al. Selective inhibition of matrix metalloproteinase-9 attenuates secondary damage resulting from severe traumatic brain injury. PLoS One, 8, 2013, e76904.
107. 107 Hayashi, T., Kaneko, Y., Yu, S., et al. Quantitative analyses of matrix metalloproteinase activity after traumatic brain injury in adult rats. Brain Res 1280 (2009), 172–177.
108. 108 Asahi, M., Asahi, K., Jung, J.C., et al. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab 20 (2000), 1681–1689.
109. 109 Jia, F., Yin, Y.H., Gao, G.Y., et al. MMP-9 inhibitor SB-3CT attenuates behavioral impairments and hippocampal loss after traumatic brain injury in rat. J Neurotrauma 31 (2014), 1225–1234.
110. 110 Lee, M., Chen, Z., Tomlinson, B.N., et al. Water-soluble MMP-9 inhibitor reduces lesion volume after severe traumatic brain injury. ACS Chem Neurosci 6 (2015), 1658–1664.
111. 111 Vink, R., van den Heuvel, C., Substance P antagonists as a therapeutic approach to improving outcome following traumatic brain injury. Neurotherapeutics 7 (2010), 74–80.
112. 112 Donkin, J.J., Vink, R., Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 23 (2010), 293–299.
113. 113 Nimmo, A.J., Cernak, I., Heath, D.L., et al. Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats. Neuropeptides 38 (2004), 40–47.
114. 114 Zacest, A.C., Vink, R., Manavis, J., et al. Substance P immunoreactivity increases following human traumatic brain injury. Acta Neurochir Suppl 106 (2010), 211–216.
115. 115 Donkin, J.J., Nimmo, A.J., Cernak, I., et al. Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury. J Cereb Blood Flow Metab 29 (2009), 1388–1398.
116. 116 Donkin, J.J., Cernak, I., Blumbergs, P.C., et al. A substance P antagonist reduces axonal injury and improves neurologic outcome when administered up to 12 hours after traumatic brain injury. J Neurotrauma 28 (2011), 217–224.
117. 117 Turner, R.J., Helps, S.C., Thornton, E., et al. A substance P antagonist improves outcome when administered 4 h after onset of ischaemic stroke. Brain Res 1393 (2011), 84–90.
118. 118 Yao, X., Uchida, K., Papadopoulos, M.C., et al. Mildly reduced brain swelling and improved neurological outcome in aquaporin-4 knockout mice following controlled cortical impact brain injury. J Neurotrauma 32 (2015), 1458–1464.
119. 119 Papadopoulos, M.C., Manley, G.T., Krishna, S., et al. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 18 (2004), 1291–1293.
120. 120 Ding, J.Y., Kreipke, C.W., Speirs, S.L., et al. Hypoxia-inducible factor-1alpha signaling in aquaporin upregulation after traumatic brain injury. Neurosci Lett 453 (2009), 68–72.
121. 121 Shenaq, M., Kassem, H., Peng, C., et al. Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1alpha after traumatic brain injury (TBI). J Neurol Sci 323 (2012), 134–140.
122. 122 Dardiotis, E., Paterakis, K., Tsivgoulis, G., et al. AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury. J Neurotrauma 31 (2014), 1920–1926.
123. 123 Fukuda, A.M., Adami, A., Pop, V., et al. Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery. J Cereb Blood Flow Metab 33 (2013), 1621–1632.
124. 124 Chen, H., Luo, J., Kintner, D.B., et al. Na(+)-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. J Cereb Blood Flow Metab 25 (2005), 54–66.
125. 125 Watanabe, M., Fukuda, A., Development and regulation of chloride homeostasis in the central nervous system. Front Cell Neurosci, 9, 2015, 371.
126. 126 Lu, K.T., Cheng, N.C., Wu, C.Y., et al. NKCC1-mediated traumatic brain injury-induced brain edema and neuron death via Raf/MEK/MAPK cascade. Crit Care Med 36 (2008), 917–922.
127. 127 Yan, Y., Dempsey, R.J., Flemmer, A., et al. Inhibition of Na(+)-K(+)-Cl(-) cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain Res 961 (2003), 22–31.
128. 128 Ameli, P.A., Ameli, N.J., Gubernick, D.M., et al. Role of vasopressin and its antagonism in stroke related edema. J Neurosci Res 92 (2014), 1091–1099.
129. 129 Huang, W.D., Pan, J., Xu, M., et al. Changes and effects of plasma arginine vasopressin in traumatic brain injury. J Endocrinol Invest 31 (2008), 996–1000.
130. 130 Szmydynger-Chodobska, J., Zink, B.J., Chodobski, A., Multiple sites of vasopressin synthesis in the injured brain. J Cereb Blood Flow Metab 31 (2011), 47–51.
131. 131 Filippidis, A.S., Liang, X., Wang, W., et al. Real-time monitoring of changes in brain extracellular sodium and potassium concentrations and intracranial pressure after selective vasopressin-1a receptor inhibition following focal traumatic brain injury in rats. J Neurotrauma 31 (2014), 1258–1267.
132. 132 Marmarou, C.R., Liang, X., Abidi, N.H., et al. Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury. Brain Res 1581 (2014), 89–102.
133. 133 Krieg, S.M., Sonanini, S., Plesnila, N., et al. Effect of small molecule vasopressin V1a and V2 receptor antagonists on brain edema formation and secondary brain damage following traumatic brain injury in mice. J Neurotrauma 32 (2015), 221–227.
134. 134 Chen, M., Dong, Y., Simard, J.M., Functional coupling between sulfonylurea receptor type 1 and a nonselective cation channel in reactive astrocytes from adult rat brain. J Neurosci 23 (2003), 8568–8577.
135. 135 Walcott, B.P., Kahle, K.T., Simard, J.M., Novel treatment targets for cerebral edema. Neurotherapeutics 9 (2012), 65–72.
136. 136 Simard, J.M., Chen, M., Tarasov, K.V., et al. Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 12 (2006), 433–440.
137. 137 Kunte, H., Busch, M.A., Trostdorf, K., et al. Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas. Ann Neurol 72 (2012), 799–806.
138. 138 Kunte, H., Schmidt, S., Eliasziw, M., et al. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke 38 (2007), 2526–2530.
139. 139 Simard, J.M., Kilbourne, M., Tsymbalyuk, O., et al. Key role of sulfonylurea receptor 1 in progressive secondary hemorrhage after brain contusion. J Neurotrauma 26 (2009), 2257–2267.
140. 140 Zweckberger, K., Hackenberg, K., Jung, C.S., et al. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury. Neuroscience 272 (2014), 199–206.
141. 141 Sheth, K.N., Kimberly, W.T., Elm, J.J., et al. Pilot study of intravenous glyburide in patients with a large ischemic stroke. Stroke 45 (2014), 281–283.
142. 142 Kimberly, W.T., Battey, T.W., Pham, L., et al. Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care 20 (2014), 193–201.
143. 143 Diaz-Arrastia, R., Kochanek, P.M., Bergold, P., et al. Pharmacotherapy of traumatic brain injury: state of the science and the road forward: report of the Department of Defense Neurotrauma Pharmacology Workgroup. J Neurotrauma 31 (2014), 135–158.