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Preclinical Models of Intracerebral Hemorrhage: A Translational Perspective

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Abstract

Intracerebral hemorrhage (ICH) is a devastating and relatively common disease affecting as many as 50,000 people annually in the United States alone. ICH remains associated with poor outcome, and approximately 40–50% of afflicted patients will die within 30 days. In reports from the NIH and AHA, the importance of developing clinically relevant models of ICH that will extend our understanding of the pathophysiology of the disease and target new therapeutic approaches was emphasized. Traditionally, preclinical ICH research has most commonly utilized two paradigms: clostridial collagenase-induced hemorrhage and autologous blood injection. In this article, the use of various species is examined in the context of the different model types for ICH, and a mechanistic approach is considered in evaluating the numerous breakthroughs in our current fund of knowledge. Each of the model types has its inherent strengths and weaknesses and has the potential to further our understanding of the pathophysiology and treatment of ICH. In particular, transgenic rodent models may be helpful in addressing genetic influences on recovery from ICH.

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References

  1. Broderick JP, Adams HP Jr., Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30(4):905–15.

    PubMed  CAS  Google Scholar 

  2. Priorities for clinical research in intracerebral hemorrhage: report from a National Institute of Neurological Disorders and Stroke workshop. Stroke 2005;36(3):e23–41.

    Google Scholar 

  3. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke 2007;38(6):2001–23.

    Article  PubMed  Google Scholar 

  4. McCarron MO, Weir CJ, Muir KW, et al. Effect of apolipoprotein E genotype on in-hospital mortality following intracerebral haemorrhage. Acta Neurol Scand 2003;107(2):106–9.

    Article  PubMed  CAS  Google Scholar 

  5. Rosenberg GA, Estrada E, Wesley M, Kyner WT. Autoradiographic patterns of brain interstitial fluid flow after collagenase-induced haemorrhage in rat. Acta Neurochir Suppl (Wien) 1990;51:280–2.

    CAS  Google Scholar 

  6. Enzmann DR, Britt RH, Lyons BE, Buxton JL, Wilson DA. Natural history of experimental intracerebral hemorrhage: sonography, computed tomography and neuropathology. AJNR Am J Neuroradiol 1981;2(6):517–26.

    PubMed  CAS  Google Scholar 

  7. Matsushita K, Meng W, Wang X, et al. Evidence for apoptosis after intercerebral hemorrhage in rat striatum. J Cereb Blood Flow Metab 2000;20(2):396–404.

    Article  PubMed  CAS  Google Scholar 

  8. Yang GY, Betz AL, Chenevert TL, Brunberg JA, Hoff JT. Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood–brain barrier permeability in rats. J Neurosurg 1994;81(1):93–102.

    PubMed  CAS  Google Scholar 

  9. Deinsberger W, Hartmann M, Vogel J, et al. Local fibrinolysis and aspiration of intracerebral hematomas in rats. An experimental study using MR monitoring. Neurol Res 1998;20(4):349–52.

    PubMed  CAS  Google Scholar 

  10. Bullock R, Brock-Utne J, van Dellen J, Blake G. Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow. Surg Neurol 1988;29(2):101–7.

    Article  PubMed  CAS  Google Scholar 

  11. Laurent JP, Molinari GF, Oakley JC. Primate model of cerebral hematoma. J Neuropathol Exp Neurol 1976;35(5):560–8.

    Article  PubMed  CAS  Google Scholar 

  12. Tomita H, Ito U, Ohno K, Hirakawa K. Chronological changes in brain edema induced by experimental intracerebral hematoma in cats. Acta Neurochir Suppl (Wien) 1994;60:558–60.

    CAS  Google Scholar 

  13. Kobari M, Gotoh F, Tomita M, et al. Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats. Stroke 1988;19(8):991–6.

    PubMed  CAS  Google Scholar 

  14. Steiner L, Lofgren J, Zwetnow NN. Characteristics and limits of tolerance in repeated subarachnoid hemorrhage in dogs. Acta Neurol Scand 1975;52(4):241–67.

    PubMed  CAS  Google Scholar 

  15. Takasugi S, Ueda S, Matsumoto K. Chronological changes in spontaneous intracerebral hematoma—an experimental and clinical study. Stroke 1985;16(4):651–8.

    PubMed  CAS  Google Scholar 

  16. Lillehei KO, Chandler WF, Knake JE. Real time ultrasound characteristics of the acute intracerebral hemorrhage as studied in the canine model. Neurosurgery 1984;14(1):48–51.

    Article  PubMed  CAS  Google Scholar 

  17. Sussman BJ, Barber JB, Goald H. Experimental intracerebral hematoma. Reduction of oxygen tension in brain and cerebrospinal fluid. J Neurosurg 1974;41(2):177–86.

    PubMed  CAS  Google Scholar 

  18. Sugi T, Fujishima M, Omae T. Lactate and pyruvate concentrations, and acid-base balance of cerebrospinal fluid in experimentally induced intracerebral and subarachnoid hemorrhage in dogs. Stroke 1975;6(6):715–9.

    PubMed  CAS  Google Scholar 

  19. Weingarten K, Zimmerman RD, Deo-Narine V, Markisz J, Cahill PT, Deck MD. MR imaging of acute intracranial hemorrhage: findings on sequential spin-echo and gradient-echo images in a dog model. AJNR Am J Neuroradiol 1991;12(3):457–67.

    PubMed  CAS  Google Scholar 

  20. Lee EJ, Hung YC. Marked anemic hypoxia deteriorates cerebral hemodynamics and brain metabolism during massive intracerebral hemorrhage. J Neurol Sci 2001;190(1–2):3–10.

    Article  PubMed  CAS  Google Scholar 

  21. Yin W, Tibbs R, Aoki K, Badr A, Zhang J. Metabolic alterations in cerebrospinal fluid from double hemorrhage model of dogs. Acta Neurochir Suppl 2002;81:257–63.

    PubMed  CAS  Google Scholar 

  22. Mukai H, Yamashita J, Kitamura A, Ito H. Stereotactic Aqua-Stream and Aspirator in the treatment of intracerebral hematoma. An experimental study. Stereotact Funct Neurosurg 1991;57(4):221–7.

    Article  PubMed  CAS  Google Scholar 

  23. Qureshi AI, Wilson DA, Hanley DF, Traystman RJ. Pharmacologic reduction of mean arterial pressure does not adversely affect regional cerebral blood flow and intracranial pressure in experimental intracerebral hemorrhage. Crit Care Med 1999;27(5):965–71.

    Article  PubMed  CAS  Google Scholar 

  24. Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation of cerebral blood flow surrounding acute (6–22 h) intracerebral hemorrhage. Neurology 2001;57(1):18–24.

    Article  PubMed  CAS  Google Scholar 

  25. Qureshi AI, Wilson DA, Traystman RJ. Treatment of elevated intracranial pressure in experimental intracerebral hemorrhage: comparison between mannitol and hypertonic saline. Neurosurgery 1999;44(5):1055–63; discussion 63–4.

    Article  PubMed  CAS  Google Scholar 

  26. Qureshi AI, Suri MF, Ringer AJ, Guterman LR, Hopkins LN. Regional intraparenchymal pressure differences in experimental intracerebral hemorrhage: effect of hypertonic saline. Crit Care Med 2002;30(2):435–41.

    Article  PubMed  Google Scholar 

  27. Ware ML, Nemani VM, Meeker M, Lee C, Morabito DJ, Manley GT. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 2005;57(4):727–36; discussion -36.

    Article  PubMed  Google Scholar 

  28. Mun-Bryce S, Wilkerson AC, Papuashvili N, Okada YC. Recurring episodes of spreading depression are spontaneously elicited by an intracerebral hemorrhage in the swine. Brain Res 2001;888(2):248–55.

    Article  PubMed  CAS  Google Scholar 

  29. Mun-Bryce S, Wilkerson A, Pacheco B, et al. Depressed cortical excitability and elevated matrix metalloproteinases in remote brain regions following intracerebral hemorrhage. Brain Res 2004;1026(2):227–34.

    Article  PubMed  CAS  Google Scholar 

  30. Mun-Bryce S, Roberts LJ, Hunt WC, Bartolo A, Okada Y. Acute changes in cortical excitability in the cortex contralateral to focal intracerebral hemorrhage in the swine. Brain Res 2004;1026(2):218–26.

    Article  PubMed  CAS  Google Scholar 

  31. 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;1073–1074:481–90.

    Article  PubMed  CAS  Google Scholar 

  32. 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(9457):387–97.

    PubMed  Google Scholar 

  33. Wagner KR, Xi G, 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(3):491–8.

    PubMed  CAS  Google Scholar 

  34. Thiex R, Kuker W, Muller HD, et al. The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage. Neurol Res 2003;25(3):254–62.

    Article  PubMed  CAS  Google Scholar 

  35. Thiex R, Weis J, Krings T, et al. Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages. J Neurosurg 2007;106(2):314–20.

    Article  PubMed  CAS  Google Scholar 

  36. Hemphill JC III, Morabito D, Farrant M, Manley GT. Brain tissue oxygen monitoring in intracerebral hemorrhage. Neurocrit Care 2005;3(3):260–70.

    Article  PubMed  Google Scholar 

  37. Wagner KR, Xi G, Hua Y, et al. Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter. Stroke 1996;27(3):490–7.

    PubMed  CAS  Google Scholar 

  38. Wagner KR, Xi G, Hua Y, Kleinholz M, de Courten-Myers GM, Myers RE. Early metabolic alterations in edematous perihematomal brain regions following experimental intracerebral hemorrhage. J Neurosurg 1998;88(6):1058–65.

    PubMed  CAS  Google Scholar 

  39. Wagner KR, Packard BA, Hall CL, et al. Protein oxidation and heme oxygenase-1 induction in porcine white matter following intracerebral infusions of whole blood or plasma. Dev Neurosci 2002;24(2–3):154–60.

    Article  PubMed  CAS  Google Scholar 

  40. Wagner KR, Beiler S, Beiler C, et al. Delayed profound local brain hypothermia markedly reduces interleukin-1beta gene expression and vasogenic edema development in a porcine model of intracerebral hemorrhage. Acta Neurochir Suppl 2006;96:177–82.

    Article  PubMed  CAS  Google Scholar 

  41. 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 (Noisy-le-grand) 2000;46(3):597–608.

    CAS  Google Scholar 

  42. Gong Y, Tian H, Xi G, Keep RF, Hoff JT, Hua Y. Systemic zinc protoporphyrin administration reduces intracerebral hemorrhage-induced brain injury. Acta Neurochir Suppl 2006;96:232–6.

    Article  PubMed  CAS  Google Scholar 

  43. Kaufman HH, Pruessner JL, Bernstein DP, Borit A, Ostrow PT, Cahall DL. A rabbit model of intracerebral hematoma. Acta Neuropathol (Berl) 1985;65(3–4):318–21.

    Article  CAS  Google Scholar 

  44. Gustafsson O, Rossitti S, Ericsson A, Raininko R. MR imaging of experimentally induced intracranial hemorrhage in rabbits during the first 6 hours. Acta Radiol 1999;40(4):360–8.

    Article  PubMed  CAS  Google Scholar 

  45. Alemany Ripoll M, Gustafsson O, Siosteen B, Olsson Y, Raininko R. MR follow-up of small experimental intracranial haemorrhages from hyperacute to subacute phase. Acta Radiol 2002;43(1):2–9.

    PubMed  Google Scholar 

  46. Narayan RK, Narayan TM, Katz DA, Kornblith PL, Murano G. Lysis of intracranial hematomas with urokinase in a rabbit model. J Neurosurg 1985;62(4):580–6.

    PubMed  CAS  Google Scholar 

  47. Thai QA, Pradilla G, Legnani FG, Kretzer RM, Hsu W, Tamargo RJ. Lysis of intracerebral hematoma with stereotactically implanted tissue plasminogen activator polymers in a rabbit model. J Neurosurg 2006;105(3):424–9.

    Article  PubMed  CAS  Google Scholar 

  48. Qureshi AI, Ali Z, Suri MF, et al. Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: an in vivo microdialysis study. Crit Care Med 2003;31(5):1482–9.

    Article  PubMed  CAS  Google Scholar 

  49. Qureshi AI, Ling GS, Khan J, et al. Quantitative analysis of injured, necrotic, and apoptotic cells in a new experimental model of intracerebral hemorrhage. Crit Care Med 2001;29(1):152–7.

    Article  PubMed  CAS  Google Scholar 

  50. Koeppen AH, Dickson AC, McEvoy JA. The cellular reactions to experimental intracerebral hemorrhage. J Neurol Sci 1995;134(Suppl):102–12.

    Article  PubMed  Google Scholar 

  51. Koeppen AH, Dickson AC, Smith J. Heme oxygenase in experimental intracerebral hemorrhage: the benefit of tin-mesoporphyrin. J Neuropathol Exp Neurol 2004;63(6):587–97.

    PubMed  CAS  Google Scholar 

  52. Aydin MD, Erdogan AR, Cevli SC, Gundogdu C, Dane S, Diyarbakirli S. Ganglionary mechanisms of spasticity and ileus in cerebral hemorrhage: an experimental study. Int J Dev Neurosci 2006;24(7):455–9.

    Article  PubMed  Google Scholar 

  53. Karwacki Z, Kowianski P, Morys J, Dziewiatkowski J, Kaczmarek E, Suchorzewska J. Effect of sevoflurane on intracranial pressure and cardiovascular function in rabbits with experimental intracerebral haematoma. Med Sci Monit 2001;7(2):212–7.

    PubMed  CAS  Google Scholar 

  54. Bullock R, Mendelow AD, Teasdale GM, Graham DI. Intracranial haemorrhage induced at arterial pressure in the rat. Part 1: Description of technique, ICP changes and neuropathological findings. Neurol Res 1984;6(4):184–8.

    PubMed  CAS  Google Scholar 

  55. Sinar EJ, Mendelow AD, Graham DI, Teasdale GM. Experimental intracerebral hemorrhage: effects of a temporary mass lesion. J Neurosurg 1987;66(4):568–76.

    PubMed  CAS  Google Scholar 

  56. Kingman TA, Mendelow AD, Graham DI, Teasdale GM. Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology. J Neuropathol Exp Neurol 1988;47(2):128–37.

    Article  PubMed  CAS  Google Scholar 

  57. Nath FP, Jenkins A, Mendelow AD, Graham DI, Teasdale GM. Early hemodynamic changes in experimental intracerebral hemorrhage. J Neurosurg 1986;65(5):697–703.

    Article  PubMed  CAS  Google Scholar 

  58. Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 1998;89(6):991–6.

    PubMed  CAS  Google Scholar 

  59. Hua Y, Xi G, Keep RF, Hoff JT. Complement activation in the brain after experimental intracerebral hemorrhage. J Neurosurg 2000;92(6):1016–22.

    PubMed  CAS  Google Scholar 

  60. Xi G, Hua Y, Keep RF, Younger JG, Hoff JT. Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke 2001;32(1):162–7.

    Article  PubMed  CAS  Google Scholar 

  61. Peeling J, Del Bigio MR, Corbett D, Green AR, Jackson DM. Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke. Neuropharmacology 2001;40(3):433–9.

    Article  PubMed  CAS  Google Scholar 

  62. Wang X, Mori T, Sumii T, Lo EH. Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons: caspase activation and oxidative stress. Stroke 2002;33(7):1882–8.

    Article  PubMed  CAS  Google Scholar 

  63. Qureshi AI, Suri MF, Ostrow PT, et al. Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery 2003;52(5):1041–7; discussion 7–8.

    Article  PubMed  Google Scholar 

  64. Allan SM, Rothwell NJ. Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci 2003;358(1438):1669–77.

    Article  PubMed  CAS  Google Scholar 

  65. Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007;27(5):894–908.

    PubMed  CAS  Google Scholar 

  66. Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997;336(15):1066–71.

    Article  PubMed  CAS  Google Scholar 

  67. Mayne M, Ni W, Yan HJ, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage. Stroke 2001;32(1):240–8.

    PubMed  CAS  Google Scholar 

  68. Wagner KR. Modeling intracerebral hemorrhage: glutamate, nuclear factor-kappa B signaling and cytokines. Stroke 2007;38(2 Suppl):753–8.

    Article  PubMed  CAS  Google Scholar 

  69. 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(4):680–6.

    PubMed  CAS  Google Scholar 

  70. Masada T, Hua Y, Xi G, et al. Overexpression of interleukin-1 receptor antagonist reduces brain edema induced by intracerebral hemorrhage and thrombin. Acta Neurochir Suppl 2003;86:463–7.

    PubMed  CAS  Google Scholar 

  71. Sinn DI, Chu K, Lee ST, et al. Pharmacological induction of heat shock protein exerts neuroprotective effects in experimental intracerebral hemorrhage. Brain Res 2007;1135(1):167–76.

    Article  PubMed  CAS  Google Scholar 

  72. Zhao X, Zhang Y, Strong R, Grotta JC, Aronowski J. 15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-gamma, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab 2006;26(6):811–20.

    Article  PubMed  CAS  Google Scholar 

  73. Wang J, Rogove AD, Tsirka AE, Tsirka SE. Protective role of tuftsin fragment 1–3 in an animal model of intracerebral hemorrhage. Ann Neurol 2003;54(5):655–64.

    Article  PubMed  CAS  Google Scholar 

  74. Imamura N, Hida H, Aihara N, et al. Neurodegeneration of substantia nigra accompanied with macrophage/microglia infiltration after intrastriatal hemorrhage. Neurosci Res 2003;46(3):289–98.

    Article  PubMed  CAS  Google Scholar 

  75. Colton CA, Gilbert DL. Microglia, an in vivo source of reactive oxygen species in the brain. Adv Neurol 1993;59:321–6.

    PubMed  CAS  Google Scholar 

  76. Hanisch UK. Microglia as a source and target of cytokines. Glia 2002;40(2):140–55.

    Article  PubMed  Google Scholar 

  77. Koeppen AH. The history of iron in the brain. J Neurol Sci 1995;134(Suppl):1–9.

    Article  PubMed  CAS  Google Scholar 

  78. Van Beek J, Chan P, Bernaudin M, Petit E, MacKenzie ET, Fontaine M. Glial responses, clusterin, and complement in permanent focal cerebral ischemia in the mouse. Glia 2000;31(1):39–50.

    Article  PubMed  Google Scholar 

  79. Wang J, Tsirka SE. Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage. Neurocrit Care 2005;3(1):77–85.

    Article  PubMed  CAS  Google Scholar 

  80. Gong C, Hoff JT, Keep RF. Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res 2000;871(1):57–65.

    Article  PubMed  CAS  Google Scholar 

  81. Hickenbottom SL, Grotta JC, Strong R, Denner LA, Aronowski J. Nuclear factor-kappaB and cell death after experimental intracerebral hemorrhage in rats. Stroke 1999;30(11):2472–7; discussion 7–8.

    PubMed  CAS  Google Scholar 

  82. Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci Lett 2000;283(3):230–2.

    Article  PubMed  CAS  Google Scholar 

  83. Power C, Henry S, Del Bigio MR, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol 2003;53(6):731–42.

    Article  PubMed  CAS  Google Scholar 

  84. Wasserman JK, Schlichter LC. Neuron death and inflammation in a rat model of intracerebral hemorrhage: effects of delayed minocycline treatment. Brain Res 2007;1136(1):208–18.

    Article  PubMed  CAS  Google Scholar 

  85. Jung KH, Chu K, Jeong SW, et al. HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 2004;35(7):1744–9.

    Article  PubMed  CAS  Google Scholar 

  86. Karwacki Z, Kowianski P, Dziewiatkowski J, et al. Quantitative analysis of influence of sevoflurane on the reactivity of microglial cells in the course of the experimental model of intracerebral haemorrhage. Eur J Anaesthesiol 2006;23(10):874–81.

    Article  PubMed  CAS  Google Scholar 

  87. Karwacki Z, Kowianski P, Dziewiatowski J, et al. The effect of propofol on astro- and microglial reactivity in the course of experimental intracerebral haemorrhage in rats. Folia Neuropathol 2006;44(1):50–8.

    PubMed  CAS  Google Scholar 

  88. Yokota H, Yoshikawa M, Hirabayashi H, et al. Expression of ciliary neurotrophic factor (CNTF), CNTF receptor alpha (CNTFR-alpha) following experimental intracerebral hemorrhage in rats. Neurosci Lett 2005;377(3):170–5.

    Article  PubMed  CAS  Google Scholar 

  89. Altumbabic M, Peeling J, Del Bigio MR. Intracerebral hemorrhage in the rat: effects of hematoma aspiration. Stroke 1998;29(9):1917–22; discussion 22–3.

    PubMed  CAS  Google Scholar 

  90. Nonaka M, Yoshikawa M, Nishimura F, et al. Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats. Neurol Res 2004;26(3):265–72.

    Article  PubMed  Google Scholar 

  91. Rosenberg GA, Estrada EY, Mobashery S. Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide-induced blood–brain barrier opening in rodents: Differences in response based on strains and solvents. Brain Res 2006.

  92. Wells JE, Biernaskie J, Szymanska A, Larsen PH, Yong VW, Corbett D. Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice. Eur J Neurosci 2005;21(1):187–96.

    Article  PubMed  Google Scholar 

  93. Tang J, Liu J, Zhou C, et al. Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J Cereb Blood Flow Metab 2004;24(10):1133–45.

    Article  PubMed  CAS  Google Scholar 

  94. Lee JM, Yin K, Hsin I, et al. Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage. J Neurol Sci 2005;229–230:249–54.

    Article  PubMed  CAS  Google Scholar 

  95. Wang J, Tsirka SE. Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain 2005;128(Pt 7):1622–33.

    Article  PubMed  Google Scholar 

  96. Lee ST, Chu K, Jung KH, et al. Memantine reduces hematoma expansion in experimental intracerebral hemorrhage, resulting in functional improvement. J Cereb Blood Flow Metab 2006;26(4):536–44.

    Article  PubMed  CAS  Google Scholar 

  97. Rosenberg GA, Navratil M. Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat. Neurology 1997;48(4):921–6.

    PubMed  CAS  Google Scholar 

  98. Gong C, Boulis N, Qian J, Turner DE, Hoff JT, Keep RF. Intracerebral hemorrhage-induced neuronal death. Neurosurgery 2001;48(4):875–82; discussion 82–3.

    Article  PubMed  CAS  Google Scholar 

  99. Matz PG, Lewen A, Chan PH. Neuronal, but not microglial, accumulation of extravasated serum proteins after intracerebral hemolysate exposure is accompanied by cytochrome c release and DNA fragmentation. J Cereb Blood Flow Metab 2001;21(8):921–8.

    Article  PubMed  CAS  Google Scholar 

  100. Felberg RA, Grotta JC, Shirzadi AL, et al. Cell death in experimental intracerebral hemorrhage: the “black hole” model of hemorrhagic damage. Ann Neurol 2002;51(4):517–24.

    Article  PubMed  Google Scholar 

  101. Sinn DI, Lee ST, Chu K, et al. Combined neuroprotective effects of celecoxib and memantine in experimental intracerebral hemorrhage. Neurosci Lett 2007;411(3):238–42.

    Article  PubMed  CAS  Google Scholar 

  102. Lee ST, Chu K, Sinn DI, et al. Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage. J Neurochem 2006;96(6):1728–39.

    Article  PubMed  CAS  Google Scholar 

  103. Peeling J, Yan HJ, Corbett D, Xue M, Del Bigio MR. Effect of FK-506 on inflammation and behavioral outcome following intracerebral hemorrhage in rat. Exp Neurol 2001;167(2):341–7.

    Article  PubMed  CAS  Google Scholar 

  104. Mayne M, Fotheringham J, Yan HJ, et al. Adenosine A2A receptor activation reduces proinflammatory events and decreases cell death following intracerebral hemorrhage. Ann Neurol 2001;49(6):727–35.

    Article  PubMed  CAS  Google Scholar 

  105. Rodrigues CM, Sola S, Nan Z, et al. Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. Proc Natl Acad Sci USA 2003;100(10):6087–92.

    Article  PubMed  CAS  Google Scholar 

  106. Sayah S, Ischenko AM, Zhakhov A, Bonnard AS, Fontaine M. Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: specific increase in interleukin-6 mRNA expression. J Neurochem 1999;72(6):2426–36.

    Article  PubMed  CAS  Google Scholar 

  107. Wu G, Huang FP. Effects of venom defibrase on brain edema after intracerebral hemorrhage in rats. Acta Neurochir Suppl 2005;95:381–7.

    Article  PubMed  CAS  Google Scholar 

  108. Yang S, Nakamura T, Hua Y, et al. Intracerebral hemorrhage in complement C3-deficient mice. Acta Neurochir Suppl 2006;96:227–31.

    Article  PubMed  CAS  Google Scholar 

  109. Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G. Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg 2004;100(4):672–8.

    Article  PubMed  CAS  Google Scholar 

  110. Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF. Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 2003;23(6):629–52.

    Article  PubMed  CAS  Google Scholar 

  111. Wu J, Hua Y, Keep RF, Schallert T, Hoff JT, Xi G. Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. Brain Res 2002;953(1–2):45–52.

    Article  PubMed  CAS  Google Scholar 

  112. Tang J, Liu J, Zhou C, et al. Role of NADPH oxidase in the brain injury of intracerebral hemorrhage. J Neurochem 2005;94(5):1342–50.

    Article  PubMed  CAS  Google Scholar 

  113. Qu Y, Chen-Roetling J, Benvenisti-Zarom L, Regan RF. Attenuation of oxidative injury after induction of experimental intracerebral hemorrhage in heme oxygenase-2 knockout mice. J Neurosurg 2007;106(3):428–35.

    Article  PubMed  Google Scholar 

  114. Peeling J, Yan HJ, Chen SG, Campbell M, Del Bigio MR. Protective effects of free radical inhibitors in intracerebral hemorrhage in rat. Brain Res 1998;795(1–2):63–70.

    Article  PubMed  CAS  Google Scholar 

  115. Suzuki K, Nakazato K, Kusakabe T, Nagamine T, Sakurai H, Takatama M. Role of oxidative stress on pathogenesis of hypertensive cerebrovascular lesions. Pathology international 2007;57(3):133–9.

    Article  PubMed  CAS  Google Scholar 

  116. Nakamura T, Keep RF, Hua Y, Nagao S, Hoff JT, Xi G. Iron-induced oxidative brain injury after experimental intracerebral hemorrhage. Acta Neurochir Suppl 2006;96:194–8.

    Article  PubMed  CAS  Google Scholar 

  117. Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G. Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 2005;1039(1–2):30–6.

    Article  PubMed  CAS  Google Scholar 

  118. Winkler DT, Bondolfi L, Herzig MC, et al. Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. J Neurosci 2001;21(5):1619–27.

    PubMed  CAS  Google Scholar 

  119. 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(5):487–94.

    Article  PubMed  Google Scholar 

  120. Thiex R, Mayfrank L, Rohde V, Gilsbach JM, Tsirka SA. The role of endogenous versus exogenous tPA on edema formation in murine ICH. Exp Neurol 2004;189(1):25–32.

    Article  PubMed  CAS  Google Scholar 

  121. Weisgraber KH. Apolipoprotein E: structure–function relationships. Advances in protein chemistry 1994;45:249–302.

    Article  PubMed  CAS  Google Scholar 

  122. Alberts MJ, Graffagnino C, McClenny C, et al. ApoE genotype and survival from intracerebral haemorrhage. Lancet 1995;346(8974):575.

    Article  PubMed  CAS  Google Scholar 

  123. Sullivan PM, Mezdour H, Aratani Y, et al. Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem 1997;272(29):17972–80.

    Article  PubMed  CAS  Google Scholar 

  124. Lynch JR, Pineda JA, Morgan D, et al. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Ann Neurol 2002;51(1):113–7.

    Article  PubMed  CAS  Google Scholar 

  125. Lynch JR, Tang W, Wang H, et al. APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. J Biol Chem 2003;278(49):48529–33.

    Article  PubMed  CAS  Google Scholar 

  126. Lynch JR, Wang H, Mace B, et al. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol 2005;192(1):109–16.

    Article  PubMed  CAS  Google Scholar 

  127. Gao J, Wang H, Sheng H, et al. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care 2006;4(1):25–31.

    Article  PubMed  CAS  Google Scholar 

  128. Laskowitz DT, McKenna SE, Song P, et al. COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. J Neurotrauma 2007;24(7):1093–107.

    Article  PubMed  Google Scholar 

  129. Del Bigio MR, Yan HJ, Buist R, Peeling J. Experimental intracerebral hemorrhage in rats. Magnetic resonance imaging and histopathological correlates. Stroke 1996;27(12):2312–9; discussion 9–20.

    PubMed  Google Scholar 

  130. Orakcioglu B, Fiebach JB, Steiner T, et al. Evolution of early perihemorrhagic changes–ischemia vs. edema: an MRI study in rats. Exp Neurol 2005;193(2):369–76.

    Article  PubMed  CAS  Google Scholar 

  131. Elger B, Seega J, Brendel R. Magnetic resonance imaging study on the effect of levemopamil on the size of intracerebral hemorrhage in rats. Stroke 1994;25(9):1836–41.

    PubMed  CAS  Google Scholar 

  132. Del Bigio MR, Yan HJ, Campbell TM, Peeling J. Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats. Neurol Res 1999;21(4):415–9.

    PubMed  Google Scholar 

  133. Del Bigio MR, Yan HJ, Xue M. Intracerebral infusion of a second-generation ciliary neurotrophic factor reduces neuronal loss in rat striatum following experimental intracerebral hemorrhage. J Neurol Sci 2001;192(1–2):53–9.

    Article  PubMed  Google Scholar 

  134. Xi G, Keep RF, Hoff JT. Pathophysiology of brain edema formation. Neurosurg Clin N Am 2002;13(3):371–83.

    Article  PubMed  Google Scholar 

  135. Mendelow AD, Unterberg A. Surgical treatment of intracerebral haemorrhage. Curr Opin Crit Care 2007;13(2):169–74.

    Article  PubMed  Google Scholar 

  136. 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(5):493–8.

    Article  PubMed  Google Scholar 

  137. Stroick M, Alonso A, Fatar M, et al. Effects of simultaneous application of ultrasound and microbubbles on intracerebral hemorrhage in an animal model. Ultrasound Med Biol 2006;32(9):1377–82.

    Article  PubMed  Google Scholar 

  138. 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;96:212–7.

    Article  PubMed  CAS  Google Scholar 

  139. MacLellan CL, Davies LM, Fingas MS, Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke 2006;37(5):1266–70.

    Article  PubMed  Google Scholar 

  140. Maclellan CL, Grams J, Adams K, Colbourne F. Combined use of a cytoprotectant and rehabilitation therapy after severe intracerebral hemorrhage in rats. Brain Res 2005;1063(1):40–7.

    Article  PubMed  CAS  Google Scholar 

  141. 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(2):287–93.

    PubMed  Google Scholar 

  142. Ardizzone TD, Lu A, Wagner KR, Tang Y, Ran R, Sharp FR. Glutamate receptor blockade attenuates glucose hypermetabolism in perihematomal brain after experimental intracerebral hemorrhage in rat. Stroke 2004;35(11):2587–91.

    Article  PubMed  CAS  Google Scholar 

  143. Chu K, Jeong SW, Jung KH, et al. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab 2004;24(8):926–33.

    Article  PubMed  CAS  Google Scholar 

  144. Seyfried D, Han Y, Lu D, Chen J, Bydon A, Chopp M. Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg 2004;101(1):104–7.

    Article  PubMed  CAS  Google Scholar 

  145. Seyfried D, Ding J, Han Y, Li Y, Chen J, Chopp M. Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats. J Neurosurg 2006;104(2):313–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC, 27710, USA

    Michael Lucas James & David S. Warner

  2. Department of Medicine (Neurology), Duke University Medical Center, Durham, NC, USA

    Michael Lucas James & Daniel T. Laskowitz

  3. Department of Neurobiology, Duke University Medical Center, Durham, NC, USA

    David S. Warner & Daniel T. Laskowitz

  4. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    David S. Warner

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  1. Michael Lucas James
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Correspondence to Michael Lucas James.

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James, M.L., Warner, D.S. & Laskowitz, D.T. Preclinical Models of Intracerebral Hemorrhage: A Translational Perspective. Neurocrit Care 9, 139–152 (2008). https://doi.org/10.1007/s12028-007-9030-2

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