Intracerebral haemorrhage: Mechanisms of injury and therapeutic targets

The Lancet Neurology

Volumn 11, Issue 8, 2012, Pages 720-731

  Keep, Richard F ^a   Hua, Ya ^a   Xi, Guohua ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; AMINOCAPROIC ACID; ANTIHYPERTENSIVE AGENT; ARGATROBAN; BLOOD CLOTTING FACTOR 7A; CELECOXIB; CELL ADHESION MOLECULE; CHEMOKINE; CITICOLINE; COLLAGENASE; DEFEROXAMINE; DEXAMETHASONE; DISUFENTON SODIUM; GAVESTINEL; GLYCEROL; IBUPROFEN; INTERLEUKIN 1BETA; MANNITOL; MATRIX METALLOPROTEINASE; PIOGLITAZONE; PROTEINASE ACTIVATED RECEPTOR 1; PROTEINASE ACTIVATED RECEPTOR 3; ROSUVASTATIN; SIMVASTATIN; TAUROURSODEOXYCHOLIC ACID; THROMBIN; TISSUE PLASMINOGEN ACTIVATOR; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; WARFARIN;

ACUPUNCTURE; ASTROCYTE; BRAIN BLOOD FLOW; BRAIN EDEMA; BRAIN HEMATOMA; BRAIN HEMORRHAGE; BRAIN INJURY; BRAIN ISCHEMIA; CEREBROSPINAL FLUID; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); COMPUTER ASSISTED TOMOGRAPHY; DISEASE ASSOCIATION; EXPERIMENTAL PIG; HUMAN; HYPERTENSION; INFLAMMATION; MINIMALLY INVASIVE SURGERY; MORBIDITY; MORTALITY; NERVE CELL; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; SEIZURE; STEM CELL TRANSPLANTATION; STROKE; THROMBOCYTE TRANSFUSION;

CEREBRAL HEMORRHAGE; HUMANS; STROKE;

EID: 84863863921     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(12)70104-7     Document Type: Review

References (155)

1. van Asch CJJ, Luitse MJA, Rinkel GJE, van der Tweel I, Algra A, Klijn CJM Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010, 9:167-176.
2. Adeoye O, Broderick JP Advances in the management of intracerebral hemorrhage. Nat Rev Neurosci 2010, 6:593-601.
3. Morgenstern LB, Hemphill JC, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010, 41:2108-2129.
4. Aguilar MI, Freeman WD Spontaneous intracerebral hemorrhage. Semin Neurol 2010, 30:555-564.
5. Xi G, Keep RF, Hoff JT Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006, 5:53-63.
6. Flaherty ML Anticoagulant-associated intracerebral hemorrhage. Semin Neurol 2010, 30:565-572.
7. Cordonnier C, Al-Shahi Salman R, Wardlaw J Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007, 130:1988-2003.
8. Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009, 8:165-174. for the Microbleed Study Group.
9. Leary MC, Saver JL Annual incidence of first silent stroke in the United States: a preliminary estimate. Cerebrovasc Dis 2003, 16:280-285.
10. Lee S-H, Ryu W-S, Roh J-K Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage. Neurology 2009, 72:171-176.
11. Cordonnier C, van der Flier WM Brain microbleeds and Alzheimer's disease: innocent observation or key player?. Brain 2011, 134:335-344.
12. Werring DJ, Gregoire SM, Cipolotti L Cerebral microbleeds and vascular cognitive impairment. J Neurol Sci 2010, 299:131-135.
13. Aronowski J, Zhao X Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke 2011, 42:1781-1786.
14. Hanley DF, Syed SJ Current acute care of intracerebral hemorrhage. Rev Neurol Dis 2007, 4:10-18.
15. Qureshi AI, Mendelow AD, Hanley DF Intracerebral haemorrhage. Lancet 2009, 373:1632-1644.
16. Wagner KR Modeling intracerebral hemorrhage: glutamate, nuclear factor-kappa B signaling and cytokines. Stroke 2007, 38(2 suppl):753-758.
17. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G Volume of intracerebral hemorrhage: a powerful and easy-to-use predictor of 30-day mortality. Stroke 1993, 24:987-993.
18. Tsunoda A, Mitsuoka H, Bandai H, Endo T, Arai H, Sato K Intracranial cerebrospinal fluid measurement studies in suspected idiopathic normal pressure hydrocephalus, secondary normal pressure hydrocephalus, and brain atrophy. J Neurol Neurosurg Psychiatry 2002, 73:552-555.
19. Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke 2010, 41:54-60.
20. Dowlatshahi D, Demchuk AM, Flaherty ML, et al. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology 2011, 76:1238-1244.
21. Balami JS, Buchan AM Complications of intracerebral haemorrhage. Lancet Neurol 2012, 11:101-118.
22. Dolinskas CA, Bilaniuk LT, Zimmerman RA, Kuhl DE Computed tomography of intracerebral hematomas, I: transmission CT observations on hematoma resolution. AJR Am J Roentgenol 1977, 129:681-688.
23. Mendelow AD, Gregson BA, Mitchell PM, Murray GD, Rowan EN, Gholkar AR Surgical trial in lobar intracerebral haemorrhage (STICH II) protocol. Trials 2011, 12:124.
24. Hanley DF Intraventricular hemorrhage: severity factor and treatment target in spontaneous intracerebral hemorrhage. Stroke 2009, 40:1533-1538.
25. MacLellan CL, Silasi G, Auriat AM, Colbourne F Rodent models of intracerebral hemorrhage. Stroke 2010, 41(10 suppl):S95-S98.
26. Kirkman MA, Allan SM, Parry-Jones AR Experimental intracerebral hemorrhage: avoiding pitfalls in translational research. J Cereb Blood Flow Metab 2011, 31:2135-2151.
27. Iida S, Baumbach GL, Lavoie JL, Faraci FM, Sigmund CD, Heistad DD Spontaneous stroke in a genetic model of hypertension in mice. Stroke 2005, 36:1253-1258.
28. Wakisaka Y, Chu Y, Miller JD, Rosenberg GA, Heistad DD Spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. J Cereb Blood Flow Metab 2010, 30:56-69.
29. Burbach GJ, Vlachos A, Ghebremedhin E, et al. Vessel ultrastructure in APP23 transgenic mice after passive anti-Aβ immunotherapy and subsequent intracerebral hemorrhage. Neurobiol Aging 2007, 28:202-212.
30. Okauchi M, Hua Y, Keep RF, Morgenstern LB, Schallert T, Xi G Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration. Stroke 2010, 41:375-382.
31. Foerch C, Arai K, Jin G, et al. Experimental model of warfarin-associated intracerebral hemorrhage. Stroke 2008, 39:3397-3404.
32. Illanes S, Zhou W, Heiland S, Markus Z, Veltkamp R Kinetics of hematoma expansion in murine warfarin-associated intracerebral hemorrhage. Brain Res 2010, 1320:135-142.
33. Ginsberg MD Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 2009, 40(3 suppl):S111-S114.
34. Poungvarin N, Bhoopat W, Viriyavejakul A, et al. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N Engl J Med 1987, 316:1229-1233.
35. Misra UK, Kalita J, Vajpayee A, Phadke RV, Hadique A, Savlani V Effect of single mannitol bolus in intracerebral hemorrhage. Eur J Neurol 2007, 14:1118-1123.
36. Yu YL, Kumana CR, Lauder IJ, et al. Treatment of acute cerebral hemorrhage with intravenous glycerol: a double-blind, placebo-controlled, randomized trial. Stroke 1992, 23:967-971.
37. Lyden PD, Shuaib A, Lees KR, et al. Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial. Stroke 2007, 38:2262-2269.
38. Haley EC, Thompson JLP, Levin B, et al. Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies. Stroke 2005, 36:1006-1010.
39. Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005, 365:387-397. for the STICH investigators.
40. Morgan T, Zuccarello M, Narayan R, Keyl P, Lane K, Hanley D Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl 2008, 105:147-151.
41. Newell DW, Shah MM, Wilcox R, et al. Minimally invasive evacuation of spontaneous intracerebral hemorrhage using sonothrombolysis. J Neurosurg 2011, 115:592-601.
42. Imberti R, Pietrobono L, Klersy C, Gamba G, Iotti G, Cornara G Intraoperative intravenous administration of rFVIIa and hematoma volume after early surgery for spontaneous intracerebral hemorrhage: a randomized prospective phase II study. Minerva Anestesiol 2012, 78:168-175.
43. Qureshi AI, Palesch YY, Martin R, et al. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol 2010, 67:570-576.
44. Anderson CS, Huang Y, Arima H, et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke 2010, 41:307-312.
45. Butcher K, Jeerakathil T, Emery D, et al. The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial: ICH ADAPT. Int J Stroke 2010, 5:227-233.
46. Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008, 358:2127-2137.
47. Platelet transfusion in cerebral hemorrhage "PATCH" The Internet Stroke Center, (accessed May 24, 2012). http://www.strokecenter.org/trials/clinicalstudies/platelet-transfusion-in-cerebral-hemorrhage/description.
48. Antifibrinolytic therapy in acute intracerebral hemorrhage "ATICH" The Internet Stroke Center, (accessed May 24, 2012). http://www.strokecenter.org/trials/clinicalstudies/antifibrinolytic-therapy-in-acute-intracerebral-hemorrhage/description.
49. Secades JJ, Alvarez-Sabin J, Rubio F, et al. Citicoline in intracerebral haemorrhage: a double-blind, randomized, placebo-controlled, multi-centre pilot study. Cerebrovasc Dis 2006, 21:380-385.
50. Iranmanesh F, Vakilian A Efficiency of citicoline in increasing muscular strength of patients with nontraumatic cerebral hemorrhage: a double-blind randomized clinical trial. J Stroke Cerebrovasc Dis 2008, 17:153-155.
51. Tapia-Perez H, Sanchez-Aguilar M, Torres-Corzo JG, et al. Use of statins for the treatment of spontaneous intracerebral hemorrhage: results of a pilot study. Cent Eur Neurosurg 2009, 70:15-20.
52. Gonzales NR, Shah J, Sangha N, et al. Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC). Int J Stroke 2012, published online Feb 20. 10.1111/j.1747-4949.2011.00761.x.
53. Selim M, Yeatts S, Goldstein JN, et al. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke 2011, 42:3067-3074.
54. Innovative strategies for treating intra-cerebral hemorrhage (ICH) The Internet Stroke Center, (accessed May 24, 2012). http://www.strokecenter.org/trials/clinicalstudies/innovative-strategies-for-treating-intra-cerebral-hemorrhage-ich/description.
55. Thiex R, Kuker W, Jungbluth P, et al. Minor inflammation after surgical evacuation compared with fibrinolytic therapy of experimental intracerebral hemorrhages. Neurol Res 2005, 27:493-498.
56. Wagner KR, Xi GH, Hua Y, et al. Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection. J Neurosurg 1999, 90:491-498.
57. Morgenstern LB, Demchuk AM, Kim DH, Frankowski RF, Grotta JC Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage. Neurology 2001, 56:1294-1299.
58. Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005, 352:777-785.
59. Diringer MN, Skolnick BE, Mayer SA, et al. Thromboembolic events with recombinant activated factor VII in spontaneous intracerebral hemorrhage: results from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Stroke 2010, 41:48-53.
60. Naidech AM, Liebling SM, Rosenberg NF, et al. Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage. Neurocrit Care 2012, 16:82-87.
61. Kawai N, Nakamura T, Nagao S Early hemostatic therapy using recombinant factor VIIa in a collagenase-induced intracerebral hemorrhage model in rats. Acta Neurochir Suppl 2006, 96:212-217.
62. Illanes S, Zhou W, Schwarting S, Heiland S, Veltkamp R Comparative effectiveness of hemostatic therapy in experimental warfarin-associated intracerebral hemorrhage. Stroke 2011, 42:191-195.
63. Wu G, Bao X, Xi G, Keep RF, Thompson BG, Hua Y Brain injury after intracerebral hemorrhage in spontaneously hypertensive rats. J Neurosurg 2011, 114:1805-1811.
64. Benveniste H, Kim KR, Hedlund LW, Kim JW, Friedman AH Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure. J Neurosurg 2000, 92:100-107.
65. Liu J, Gao BB, Clermont AC, et al. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med 2011, 17:206-210.
66. Mayer SA, Lignelli A, Fink ME, et al. Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study. Stroke 1998, 29:1791-1798.
67. Qureshi AI, Wilson DA, Hanley DF, Traystman RJ No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage. Neurology 1999, 52:266-272.
68. Tanaka A, Yoshinaga S, Nakayama Y, Kimura M, Tomonaga M Cerebral blood flow and clinical outcome in patients with thalamic hemorrhages: a comparison with putaminal hemorrhages. J Neurol Sci 1996, 144:191-197.
69. Herweh C, Juttler E, Schellinger PD, et al. Evidence against a perihemorrhagic penumbra provided by perfusion computed tomography. Stroke 2007, 38:2941-2947.
70. Murakami M, Fujioka S, Oyama T, Kuroda J, Tajiri S, Kuratsu J Serial changes in the regional cerebral blood flow of patients with hypertensive intracerebral hemorrhage: long-term follow-up SPECT study. J Neurosurg Sci 2005, 49:117-124.
71. Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab 2001, 21:804-810.
72. Kim-Han JS, Kopp SJ, Dugan LL, Diringer MN Perihematomal mitochondrial dysfunction after intracerebral hemorrhage. Stroke 2006, 37:2457-2462.
73. Wagner KR, Xi G, Hua Y, et al. Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter. Stroke 1996, 27:490-497.
74. Xi G, Reiser G, Keep RF The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?. J Neurochem 2003, 84:3-9.
75. Liu D-Z, Ander BP, Xu H, et al. Blood-brain barrier breakdown and repair by Src after thrombin-induced injury. Ann Neurol 2010, 67:526-533.
76. Lee KR, Kawai N, Kim S, Sagher O, Hoff JT Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg 1997, 86:272-278.
77. Vaughan PJ, Pike CJ, Cotman CW, Cunningham DD Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J Neurosci 1995, 15:5389-5401.
78. Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann KG, Reiser G The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc Natl Acad Sci USA 2000, 97:2264-2269.
79. Jiang Y, Wu J, Hua Y, et al. Thrombin-receptor activation and thrombin-induced brain tolerance. J Cereb Blood Flow Metab 2002, 22:404-410.
80. Moller T, Hanisch UK, Ransom BR Thrombin-induced activation of cultured rodent microglia. J Neurochem 2000, 75:1539-1547.
81. Donovan FM, Pike CJ, Cotman CW, Cunningham DD Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci 1997, 17:5316-5326.
82. Ardizzone TD, Zhan X, Ander BP, Sharp FR SRC kinase inhibition improves acute outcomes after experimental intracerebral hemorrhage. Stroke 2007, 38:1621-1625.
83. Liu DZ, Sharp FR The dual role of SRC kinases in intracerebral hemorrhage. Acta Neurochir Suppl 2011, 111:77-81.
84. Xi G, Reiser G, Keep RF The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?. J Neurochem 2003, 84:3-9.
85. Ohnishi M, Katsuki H, Fujimoto S, Takagi M, Kume T, Akaike A Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury. Exp Neurol 2007, 206:43-52.
86. Xue M, Hollenberg MD, Demchuk A, Yong VW Relative importance of proteinase-activated receptor-1 versus matrix metalloproteinases in intracerebral hemorrhage-mediated neurotoxicity in mice. Stroke 2009, 40:2199-2204.
87. Hamada R, Matsuoka H, Wagner KR, et al. Antithrombin therapy for intracerebral hemorrhage. Stroke 2000, 31:794-795.
88. Xi G, Keep RF, Hua Y, Xiang JM, Hoff JT Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning. Stroke 1999, 30:1247-1255.
89. Hua Y, Keep RF, Gu Y, Xi G Thrombin and brain recovery after intracerebral hemorrhage. Stroke 2009, 40(3 suppl):S88-S89.
90. Yang S, Song S, Hua Y, Nakamura T, Keep RF, Xi G Effects of thrombin on neurogenesis after intracerebral hemorrhage. Stroke 2008, 39:2079-2084.
91. Niclou S, Suidan HS, Brown-Luedi M, Monard D Expression of the thrombin receptor mRNA in rat brain. Cell Mol Biol 1994, 40:421-428.
92. Weinstein JR, Gold SJ, Cunningham DD, Gall CM Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci 1995, 15:2906-2919.
93. Junge CE, Sugawara T, Mannaioni G, et al. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc Natl Acad Sci USA 2003, 100:13019-13024.
94. Wang J Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol 2010, 92:463-477.
95. Hwang BY, Appelboom G, Ayer A, et al. Advances in neuroprotective strategies: potential therapies for intracerebral hemorrhage. Cerebrovasc Dis 2011, 31:211-222.
96. Wang J, Dore S Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007, 27:894-908.
97. Sansing LH, Harris TH, Kasner SE, Hunter CA, Kariko K Neutrophil depletion diminishes monocyte infiltration and improves functional outcome after experimental intracerebral hemorrhage. Acta Neurochir Suppl 2011, 111:173-178.
98. Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol 2011, 70:646-656.
99. Rolland WB, Manaenko A, Lekic T, et al. FTY720 is neuroprotective and improves functional outcomes after intracerebral hemorrhage in mice. Acta Neurochir Suppl 2011, 111:213-217.
100. Strbian D, Kovanen PT, Karjalainen-Lindsberg ML, Tatlisumak T, Lindsberg PJ An emerging role of mast cells in cerebral ischemia and hemorrhage. Ann Med 2009, 41:438-450.
101. Lu A, Tang Y, Ran R, Ardizzone TL, Wagner KR, Sharp FR Brain genomics of intracerebral hemorrhage. J Cereb Blood Flow Metab 2006, 26:230-252.
102. Rosell A, Vilalta A, Garcia-Berrocoso T, et al. Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage. PLoS One 2011, 6:e16750.
103. Hua Y, Wu J, Keep RF, Nakamura T, Hoff JT, Xi G Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation. Neurosurgery 2006, 58:542-550.
104. Ma Q, Manaenko A, Khatibi NH, Chen W, Zhang JH, Tang J Vascular adhesion protein-1 inhibition provides antiinflammatory protection after an intracerebral hemorrhagic stroke in mice. J Cereb Blood Flow Metab 2011, 31:881-893.
105. Masada T, Hua Y, Xi G, Yang GY, Hoff JT, Keep RF Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist. J Neurosurg 2001, 95:680-686.
106. Keep RF, Xiang J, Ennis SR, et al. Blood-brain barrier function in intracerebral hemorrhage. Acta Neurochir Suppl 2008, 105:73-77.
107. Ducruet AF, Zacharia BE, Hickman ZL, et al. The complement cascade as a therapeutic target in intracerebral hemorrhage. Exp Neurol 2009, 219:398-403.
108. Hua Y, Xi G, Keep RF, Hoff JT Complement activation in the brain after experimental intracerebral hemorrhage. J Neurosurg 2000, 92:1016-1022.
109. Xi G, Hua Y, Keep RF, Younger JG, Hoff JT Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke 2001, 32:162-167.
110. Garrett MC, Otten ML, Starke RM, et al. Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Res 2009, 1298:171-177.
111. Nakamura T, Xi G, Hua Y, Schallert T, Hoff JT, Keep RF Intracerebral hemorrhage in mice: model characterization and application for genetically modified mice. J Cereb Blood Flow Metab 2004, 24:487-494.
112. Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 2002, 96:287-293.
113. Xi G, Keep RF, Hoff JT Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 1998, 89:991-996.
114. Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 2003, 34:2964-2969.
115. Zhao F, Hua Y, He Y, Keep RF, Xi G Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke 2011, 42:3587-3593.
116. Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke 2009, 40:2241-2243.
117. Wu H, Wu T, Xu X, Wang J, Wang J Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab 2011, 31:1243-1250.
118. Auriat AM, Silasi G, Wei Z, et al. Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome. Exp Neurol 2012, 234:136-143.
119. Koeppen AH, Dickson AC, Smith J Heme oxygenase in experimental intracerebral hemorrhage: the benefit of tin-mesoporphyrin. J Neuropathol Exp Neurol 2004, 63:587-597.
120. Wagner KR, Hua Y, de Courten-Myers GM, et al. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol 2000, 46:597-608.
121. Wang J, Dore S Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage. Brain 2007, 130:1643-1652.
122. Han N, Ding S-J, Wu T, Zhu Y-L Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats. Neurosci Bull 2008, 24:351-358.
123. Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 2005, 1039:30-36.
124. Chen Y-C, Chen C-M, Liu J-L, Chen S-T, Cheng M-L, Chiu DT-Y Oxidative markers in spontaneous intracerebral hemorrhage: leukocyte 8-hydroxy-2'-deoxyguanosine as an independent predictor of the 30-day outcome. J Neurosurg 2011, 115:1184-1190.
125. Nakamura T, Kuroda Y, Yamashita S, et al. Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke 2008, 39:463-469.
126. Tang J, Liu J, Zhou C, et al. Role of NADPH oxidase in the brain injury of intracerebral hemorrhage. J Neurochem 2005, 94:1342-1350.
127. Guo F, Hua Y, Wang J, Keep RF, Xi G Inhibition of carbonic anhydrase reduces brain injury after intracerebral hemorrhage. Transl Stroke Res 2012, 3:130-137.
128. Lee S-T, Chu K, Jung K-H, et al. Memantine reduces hematoma expansion in experimental intracerebral hemorrhage, resulting in functional improvement. J Cereb Blood Flow Metab 2006, 26:536-544.
129. Sharp F, Liu DZ, Zhan X, Ander BP Intracerebral hemorrhage injury mechanisms: glutamate neurotoxicity, thrombin, and Src. Acta Neurochir Suppl 2008, 105:43-46.
130. Bullock MR, Merchant RE, Carmack CA, et al. An open-label study of CP-101,606 in subjects with a severe traumatic head injury or spontaneous intracerebral hemorrhage. Ann N Y Acad Sci 1999, 890:51-58.
131. Lee KR, Drury I, Vitarbo E, Hoff JT Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage. J Neurosurg 1997, 87:73-78.
132. Mun-Bryce S, Roberts L, Bartolo A, Okada Y Transhemispheric depolarizations persist in the intracerebral hemorrhage swine brain following corpus callosal transection. Brain Res 2006, 1073-1074:481-490.
133. Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab 2011, 31:17-35.
134. Hua Y, Nakamura T, Keep RF, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg 2006, 104:305-312.
135. Delgado P, Cuadrado E, Rosell A, et al. Fas system activation in perihematomal areas after spontaneous intracerebral hemorrhage. Stroke 2008, 39:1730-1734.
136. Zhu X, Tao L, Tejima-Mandeville E, et al. Plasmalemma permeability and necrotic cell death phenotypes after intracerebral hemorrhage in mice. Stroke 2012, 43:524-531.
137. Lee S-T, Chu K, Sinn D-I, et al. Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage. J Neurochem 2006, 96:1728-1739.
138. Yang D, Han Y, Zhang J, Ding C, Anagli J, Seyfried DM Improvement in recovery after experimental intracerebral hemorrhage using a selective cathepsin B and L inhibitor. J Neurosurg 2011, 114:1110-1116.
139. He Y, Wan S, Hua Y, Keep RF, Xi G Autophagy after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 2008, 28:897-905.
140. Wang J, Fields J, Zhao C, et al. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med 2007, 43:408-414.
141. Zhao X, Sun G, Zhang J, et al. Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage. Stroke 2007, 38:3280-3286.
142. Zhao X, Grotta J, Gonzales N, Aronowski J Hematoma resolution as a therapeutic target: the role of microglia/macrophages. Stroke 2009, 40(3 suppl):S92-S94.
143. Seyfried DM, Han Y, Yang D, Ding J, Chopp M Erythropoietin promotes neurological recovery after intracerebral haemorrhage in rats. Int J Stroke 2009, 4:250-256.
144. Belayev L, Obenaus A, Zhao W, et al. Experimental intracerebral hematoma in the rat: characterization by sequential magnetic resonance imaging, behavior, and histopathology: effect of albumin therapy. Brain Res 2007, 1157:146-155.
145. Karki K, Knight RA, Han Y, et al. Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage. Stroke 2009, 40:3384-3389.
146. MacLellan CL, Clark DL, Silasi G, Colbourne F Use of prolonged hypothermia to treat ischemic and hemorrhagic stroke. J Neurotrauma 2009, 26:313-323.
147. Fingas M, Penner M, Silasi G, Colbourne F Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia. Exp Neurol 2009, 219:156-162.
148. Hua Y, Schallert T, Keep RF, Wu J, Hoff JT, Xi G Behavioral tests after intracerebral hemorrhage in the rat. Stroke 2002, 33:2478-2484.
149. Zhao X, Sun G, Zhang J, et al. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol 2007, 61:352-362.
150. Auriat AM, Colbourne F Delayed rehabilitation lessens brain injury and improves recovery after intracerebral hemorrhage in rats. Brain Res 2009, 1251:262-268.
151. Auriat AM, Grams JD, Yan RH, Colbourne F Forced exercise does not improve recovery after hemorrhagic stroke in rats. Brain Res 2006, 1109:183-191.
152. Auriat AM, Wowk S, Colbourne F Rehabilitation after intracerebral hemorrhage in rats improves recovery with enhanced dendritic complexity but no effect on cell proliferation. Behav Brain Res 2010, 214:42-47.
153. Frantzias J, Sena ES, Macleod MR, Al-Shahi Salman R Treatment of intracerebral hemorrhage in animal models: meta-analysis. Ann Neurol 2011, 69:389-399.
154. Seyfried DM, Han Y, Yang D, et al. Localization of bone marrow stromal cells to the injury site after intracerebral hemorrhage in rats. J Neurosurg 2010, 112:329-335.
155. Lee HJ, Kim MK, Kim HJ, Kim SU Human neural stem cells genetically modified to overexpress Akt1 provide neuroprotection and functional improvement in mouse stroke model. PLoS One 2009, 4:e5586.