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New Avenues for Treatment of Intracranial Hemorrhage

  • Cerebrovascular Disease and Stroke (D Greer, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

The mortality and morbidity from intracerebral hemorrhage (ICH) remain high despite advances in medical, neurologic, and surgical care during the past decade. The lessons learned from previous therapeutic trials in ICH, improved understanding of the pathophysiology of neuronal injury after ICH, and advances in imaging and pre-hospital assessment technologies provide optimism that more effective therapies for ICH are likely to emerge in the coming years. The potential new avenues for the treatment of ICH include a combination of increased utilization of minimally invasive surgical techniques with or without thrombolytic usage to evacuate or reduce the size of the hematoma; utilization of advanced imaging to improve selection of patients who are likely to benefit from reversal of coagulopathy or hemostatic therapy; ultra-early diagnosis and initiation of therapy in the ambulance; and the use of novel drugs to target the secondary injury mechanisms, including the inflammatory cascade, perihematomal edema reduction, and hemoglobin degradation products-mediated toxicity.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Lovelock CE, Molyneux AJ, Rothwell PM. Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol. 2007;6(6):487–93.

    Article  CAS  PubMed  Google Scholar 

  2. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. 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(2):167–76.

    Article  PubMed  Google Scholar 

  3. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8(4):355–69.

    Article  PubMed  Google Scholar 

  4. Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009;40(2):394–9.

    Article  PubMed  Google Scholar 

  5. Labovitz DL, Halim A, Boden-Albala B, Hauser WA, Sacco RL. The incidence of deep and lobar intracerebral hemorrhage in Whites, Blacks, and Hispanics. Neurology. 2005;65(4):518–22.

    Article  CAS  PubMed  Google Scholar 

  6. Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003;34(8):2060–5.

    Article  CAS  PubMed  Google Scholar 

  7. Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology. 2007;68(2):116–21.

    Article  CAS  PubMed  Google Scholar 

  8. McCarron MO, Nicoll JA. Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage. Ann N Y Acad Sci. 2000;903:176–9.

    Article  CAS  PubMed  Google Scholar 

  9. Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006;66(8):1175–81.

    Article  CAS  PubMed  Google Scholar 

  10. Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011;76(14):1238–44.

    Article  CAS  PubMed  Google Scholar 

  11. Delcourt C, Huang Y, Arima H, et al. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012;79(4):314–9.

    Article  PubMed  Google Scholar 

  12. Dowlatshahi D, Smith EE, Flaherty ML, Ali M, Lyden P, Demchuk AM. Small intracerebral haemorrhages are associated with less haematoma expansion and better outcomes. Int J Stroke. 2011;6(3):201–6.

    Article  PubMed  Google Scholar 

  13. Brouwers HB, Greenberg SM. Hematoma expansion following acute intracerebral hemorrhage. Cerebrovasc Dis. 2013;35(3):195–201.

    Article  PubMed  Google Scholar 

  14. Adeoye O, Broderick JP. Advances in the management of intracerebral hemorrhage. Nat Rev Neurol. 2010;6(11):593–601.

    Article  CAS  PubMed  Google Scholar 

  15. Brouwers HB, Falcone GJ, McNamara KA, et al. CTA spot sign predicts hematoma expansion in patients with delayed presentation after intracerebral hemorrhage. Neurocrit Care. 2012;17(3):421–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fisher CM. Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol. 1971;30(3):536–50.

    Article  CAS  PubMed  Google Scholar 

  17. Broderick JP, Diringer MN, Hill MD, et al. Determinants of intracerebral hemorrhage growth: an exploratory analysis. Stroke. 2007;38(3):1072–5.

    Article  CAS  PubMed  Google Scholar 

  18. Flibotte JJ, Hagan N, O'Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63(6):1059–64.

    Article  CAS  PubMed  Google Scholar 

  19. Cucchiara B, Messe S, Sansing L, Kasner S, Lyden P. Hematoma growth in oral anticoagulant related intracerebral hemorrhage. Stroke. 2008;39(11):2993–6.

    Article  CAS  PubMed  Google Scholar 

  20. Brouwers HB, Biffi A, Ayres AM, et al. Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage. Stroke. 2012;43(6):1490–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Silva Y, Leira R, Tejada J, Lainez JM, Castillo J, Davalos A. Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. Stroke. 2005;36(1):86–91.

    Article  PubMed  Google Scholar 

  22. Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38(4):1257–62.

    Article  PubMed  Google Scholar 

  23. Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology. 2007;68(12):889–94.

    Article  CAS  PubMed  Google Scholar 

  24. Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012;11(4):307–14. In this large observational study, the hypothesis that CT-angiography spot sign (contrast extravasation within the hematoma) predicts subsequent hematoma growth. Despite some concern regarding low sensitivity and inter-rater reliability, it appears to be a useful imaging diagnostic tool which, if further refined, could be of significant use in early detection of those patients at higher risk for hematoma growth

    Article  PubMed  Google Scholar 

  25. Rizos T, Dorner N, Jenetzky E, et al. Spot signs in intracerebral hemorrhage: useful for identifying patients at risk for hematoma enlargement? Cerebrovasc Dis. 2013;35(6):582–9.

    Article  PubMed  Google Scholar 

  26. Wang YH, Fan JY, Luo GD, et al. Hematoma volume affects the accuracy of computed tomographic angiography 'spot sign' in predicting hematoma expansion after acute intracerebral hemorrhage. Eur Neurol. 2011;65(3):150–5.

    Article  PubMed  Google Scholar 

  27. 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(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  28. 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 U S A. 2000;97(5):2264–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu DZ, Ander BP, Xu H, et al. Blood–brain barrier breakdown and repair by Src after thrombin-induced injury. Ann Neurol. 2010;67(4):526–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Liu DZ, Sharp FR. The dual role of SRC kinases in intracerebral hemorrhage. Acta Neurochir Suppl (Wien). 2011;111:77–81.

    Article  Google Scholar 

  31. 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(14):5316–26.

    CAS  PubMed  Google Scholar 

  32. Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010;92(4):463–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Florczak-Rzepka M, Grond-Ginsbach C, Montaner J, Steiner T. Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update. Cerebrovasc Dis. 2012;34(4):249–62.

    Article  CAS  PubMed  Google Scholar 

  34. Keep RF, Xiang J, Ennis SR, et al. Blood–brain barrier function in intracerebral hemorrhage. Acta Neurochir Suppl (Wien). 2008;105:73–7.

    Article  CAS  Google Scholar 

  35. 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(3):542–50. discussion 542–50. discussion 542–50

    Google Scholar 

  36. Rosenberg GA. Matrix metalloproteinases in neuroinflammation. Glia. 2002;39(3):279–91.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  38. Ducruet AF, Zacharia BE, Hickman ZL, et al. The complement cascade as a therapeutic target in intracerebral hemorrhage. Exp Neurol. 2009;219(2):398–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  PubMed  Google Scholar 

  41. 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  CAS  PubMed  Google Scholar 

  42. Han N, Ding SJ, Wu T, Zhu YL. Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats. Neurosci Bull. 2008;24(6):351–8.

    Article  CAS  PubMed  Google Scholar 

  43. Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M. Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke. 2008;39(4):1165–70.

    Article  CAS  PubMed  Google Scholar 

  44. Lou M, Lieb K, Selim M. The relationship between hematoma iron content and perihematoma edema: an MRI study. Cerebrovasc Dis. 2009;27(3):266–71.

    Article  CAS  PubMed  Google Scholar 

  45. 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(4):646–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Inaji M, Tomita H, Tone O, Tamaki M, Suzuki R, Ohno K. Chronological changes of perihematomal edema of human intracerebral hematoma. Acta Neurochir Suppl (Wien). 2003;86:445–8.

    CAS  Google Scholar 

  47. McCarron MO, Hoffmann KL, DeLong DM, Gray L, Saunders AM, Alberts MJ. Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology. 1999;53(9):2176–9.

    Article  CAS  PubMed  Google Scholar 

  48. Sansing LH, Messe SR, Cucchiara BL, Lyden PD, Kasner SE. Anti-adrenergic medications and edema development after intracerebral hemorrhage. Neurocrit Care. 2011;14(3):395–400.

    Article  CAS  PubMed  Google Scholar 

  49. Venkatasubramanian C, Mlynash M, Finley-Caulfield A, et al. Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke. 2011;42(1):73–80.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ. Progression of mass effect after intracerebral hemorrhage. Stroke. 1999;30(6):1167–73.

    Article  CAS  PubMed  Google Scholar 

  51. Gebel Jr JM, Jauch EC, Brott TG, et al. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33(11):2631–5.

    Article  PubMed  Google Scholar 

  52. Staykov D, Wagner I, Volbers B, et al. Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2011;42(9):2625–9.

    Article  PubMed  Google Scholar 

  53. Arima H, Wang JG, Huang Y, et al. Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial. Neurology. 2009;73(23):1963–8.

    Article  CAS  PubMed  Google Scholar 

  54. Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke. 2004;35(8):1879–85.

    Article  PubMed  Google Scholar 

  55. Olivot JM, Mlynash M, Kleinman JT, et al. MRI profile of the perihematomal region in acute intracerebral hemorrhage. Stroke. 2010;41(11):2681–3.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Pascual AM, Lopez-Mut JV, Benlloch V, Chamarro R, Soler J, Lainez MJ. Perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage at baseline and during the 1st and 2nd week: a longitudinal study. Cerebrovasc Dis. 2007;23(1):6–13.

    Article  PubMed  Google Scholar 

  57. Fainardi E, Borrelli M, Saletti A, et al. Temporal changes in perihematomal apparent diffusion coefficient values during the transition from acute to subacute phases in patients with spontaneous intracerebral hemorrhage. Neuroradiology. 2013;55(2):145–56.

    Article  PubMed  Google Scholar 

  58. Kidwell CS, Saver JL, Mattiello J, et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage. Neurology. 2001;57(9):1611–7.

    Article  CAS  PubMed  Google Scholar 

  59. Morgenstern LB, Hemphill 3rd 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(9):2108–29.

    Article  PubMed  Google Scholar 

  60. Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery vs initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomized trial. Lancet. 2005;365(9457):387–97.

    PubMed  Google Scholar 

  61. Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM. Early surgery vs initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomized trial. Lancet. 2013;382(9890):397–408. In this large, randomized multi-center trial, early surgery was tested against conservative treatment in patients with superficial (<1cm from surface) supratentorial spontaneous ICH, based on subgroup analyses from STICH I. The study again failed to show superiority of the surgical approach. The focus of surgical clot evacuation has shifted toward less invasive approaches.

    Google Scholar 

  62. 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 (Wien). 2008;105:147–51.

    Article  CAS  Google Scholar 

  63. Mould WA, Carhuapoma JR, Muschelli J, et al. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke. 2013;44(3):627–34The MISTIE trial is a series of clinical trials testing the safety and efficacy of minimally invasive methods for clot retrieval in conjunction with tissue plasminogen activator use. Its safety has been shown and planning for phase III is underway. The promising preliminary results and failure of major invasive surgery in the STICH trials have shifted the focus on this and other minimally invasive methods that might dramatically alter the landscape of ICH treatment.

    Article  CAS  PubMed  Google Scholar 

  64. Naff N, Williams MA, Keyl PM, et al. Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial. Stroke. 2011;42(11):3009–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Newell DW, Shah MM, Wilcox R, et al. Minimally invasive evacuation of spontaneous intracerebral hemorrhage using sonothrombolysis. J Neurosurg. 2011;115(3):592–601.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 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(20):2127–37 The need for improved selection and identification of ICH patients who are most likely to derive benefit from hemostatic therapy using advanced imaging or biochemical markers and 2- Targeting hematoma expansion is time sensitive. HE resulting in significant clinical deterioration occurs in 26% of patients within 1 hour of ICH onset and in an additional 12% of patients by 20 hours.

    Article  CAS  PubMed  Google Scholar 

  67. 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(1):48–53.

    Article  CAS  PubMed  Google Scholar 

  68. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke. 1997;28(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  69. Hanger HC, Geddes JA, Wilkinson TJ, Lee M, Baker AE. Warfarin-related intracerebral haemorrhage: better outcomes when reversal includes prothrombin complex concentrates. Int Med J. 2013;43(3):308–16.

    Article  CAS  Google Scholar 

  70. Dowlatshahi D, Butcher KS, Asdaghi N, et al. Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke. 2012;43(7):1812–7.

    Article  CAS  PubMed  Google Scholar 

  71. Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomized pilot trial. Lancet Neurol. 2008;7(5):391–9.

    Article  PubMed  Google Scholar 

  72. 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(5):570–6.

    Article  PubMed  Google Scholar 

  73. Butcher KS, Jeerakathil T, Hill M, et al. The intracerebral hemorrhage acutely decreasing arterial pressure trial. Stroke. 2013;44(3):620–6.

    Article  PubMed  Google Scholar 

  74. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355–65. The Intensive Blood Pressure Reduction in Acute Cerebral-2 (INTERACT-2) trial in 2839 patients confirmed the safety of rapid lowering of SBP within 6 hours of ICH onset to less than 140 mm Hg. They reported a strong trend, albeit nonsignificant, toward reduced 90-day mortality and severe disability with intensive blood pressure lowering. It showed significant improved functional outcomes in the treatment arm in a secondary ordinal analysis of 90-day modified Rankin Scale scores.

    Article  CAS  PubMed  Google Scholar 

  75. Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale. Neurocrit Care. 2011;15(3):559–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Moon JS, Janjua N, Ahmed S, et al. Prehospital neurologic deterioration in patients with intracerebral hemorrhage. Crit Care Med. 2008;36(1):172–5.

    Article  PubMed  Google Scholar 

  77. Fan JS, Huang HH, Chen YC, et al. Emergency department neurologic deterioration in patients with spontaneous intracerebral hemorrhage: incidence, predictors, and prognostic significance. Acad Emerg Med. 2012;19(2):133–8.

    Article  PubMed  Google Scholar 

  78. Audebert HJ, Saver JL, Starkman S, Lees KR, Endres M. Prehospital stroke care: new prospects for treatment and clinical research. Neurology. 2013;81(5):501–8.

    Article  CAS  PubMed  Google Scholar 

  79. 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(12):3587–93.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Shi W, Wang Z, Pu J, et al. Changes of blood–brain barrier permeability following intracerebral hemorrhage and the therapeutic effect of minocycline in rats. Acta Neurochir Suppl (Wien). 2011;110(Pt 2):61–7.

    Google Scholar 

  81. Wasserman JK, Schlichter LC. Minocycline protects the blood–brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp Neurol. 2007;207(2):227–37.

    Article  CAS  PubMed  Google Scholar 

  82. Szymanska A, Biernaskie J, Laidley D, Granter-Button S, Corbett D. Minocycline and intracerebral hemorrhage: influence of injury severity and delay to treatment. Exp Neurol. 2006;197(1):189–96.

    Article  CAS  PubMed  Google Scholar 

  83. Colbourne F, Corbett D, Zhao Z, Yang J, Buchan AM. Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model. J Cereb Blood Flow Metab. 2000;20(12):1702–8.

    Article  CAS  PubMed  Google Scholar 

  84. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.

    Article  PubMed  Google Scholar 

  85. Fingas M, Clark DL, Colbourne F. The effects of selective brain hypothermia on intracerebral hemorrhage in rats. Exp Neurol. 2007;208(2):277–84.

    Article  PubMed  Google Scholar 

  86. MacLellan CL, Girgis J, Colbourne F. Delayed onset of prolonged hypothermia improves outcome after intracerebral hemorrhage in rats. J Cereb Blood Flow Metab. 2004;24(4):432–40.

    Article  PubMed  Google Scholar 

  87. Staykov D, Wagner I, Volbers B, Doerfler A, Schwab S, Kollmar R. Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care. 2013;18(2):178–83.

    Article  PubMed  Google Scholar 

  88. Kollmar R, Juettler E, Huttner HB, et al. Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial. Int J Stroke. 2012;7(2):168–72.

    Article  PubMed  Google Scholar 

  89. Belayev L, Saul I, Busto R, et al. Albumin treatment reduces neurological deficit and protects blood–brain barrier integrity after acute intracortical hematoma in the rat. Stroke. 2005;36(2):326–31.

    Article  CAS  PubMed  Google Scholar 

  90. 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;1157:146–55.

    Article  CAS  PubMed  Google Scholar 

  91. Ginsberg MD, Palesch YY, Martin RH, et al. The albumin in acute stroke (ALIAS) multi-center clinical trial: safety analysis of part 1 and rationale and design of part 2. Stroke. 2011;42(1):119–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. 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  CAS  PubMed  Google Scholar 

  93. Chen M, Awe OO, Chen-Roetling J, Regan RF. Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage. Brain Res. 2010;1337:95–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. 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(2):375–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 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(6):2241–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wu H, Wu T, Xu X, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab. 2011;31(5):1243–50.

    Article  CAS  PubMed  Google Scholar 

  97. 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. Neurosurg Focus. 2003;15(4):ECP4.

    Article  PubMed  Google Scholar 

  98. Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009;40(3 Suppl):S90–1.

    Article  CAS  PubMed  Google Scholar 

  99. Selim M, Yeatts S, Goldstein JN, et al. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011;42(11):3067–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ji S, Kronenberg G, Balkaya M, et al. Acute neuroprotection by pioglitazone after mild brain ischemia without effect on long-term outcome. Exp Neurol. 2009;216(2):321–8.

    Article  CAS  PubMed  Google Scholar 

  101. 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. 2013;8(5):388–96.

    Article  PubMed  Google Scholar 

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Conflict of Interest

Dr. Shruti Sonni declares no potential conflicts of interest relevant to this article. Dr. Vasileios-Arsenios Lioutas declares no potential conflicts of interest relevant to this article. Dr. Magdy H. Selim is the principal investigator for a NINDS-sponsored trial (U01 NS074425).

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Authors and Affiliations

  1. Department of Neurology, Cambridge Hospital, 1493 Cambridge Street, Cambridge, MA, 02139, USA

    Shruti Sonni MD

  2. Department of Neurology, Stroke Division, Beth Israel Deaconess Medical Center, Palmer 127, 330 Brookline Avenue, Boston, MA, 02215, USA

    Vasileios-Arsenios Lioutas MD & Magdy H. Selim MD, PhD

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  1. Shruti Sonni MD
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  2. Vasileios-Arsenios Lioutas MD
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  3. Magdy H. Selim MD, PhD
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Correspondence to Magdy H. Selim MD, PhD.

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This article is part of the Topical Collection on Cerebrovascular Disease and Stroke

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Sonni, S., Lioutas, VA. & Selim, M.H. New Avenues for Treatment of Intracranial Hemorrhage. Curr Treat Options Cardio Med 16, 277 (2014). https://doi.org/10.1007/s11936-013-0277-y

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  • DOI: https://doi.org/10.1007/s11936-013-0277-y

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