Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurotherapeutics
Published in: Neurotherapeutics 3/2011

01-07-2011 | Review

Treatment Targets in Intracerebral Hemorrhage

Authors: Navdeep Sangha, Nicole R. Gonzales

Published in: Neurotherapeutics | Issue 3/2011

Login to get access

Abstract

Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease.
Appendix
Available only for authorised users
Literature
1.
Cheung RT. Update on medical and surgical management of intracerebral hemorrhage. Rev Recent Clin Trials 2007;2:174–181.PubMedCrossRef
2.
Broderick JP, Phillips SJ, Whisnant JP, O'Fallon WM, Bergstralh EJ. Incidence rates of stroke in the eighties: the end of the decline in stroke? Stroke 1989;20:577–582.PubMedCrossRef
3.
Giroud M, Gras P, Chadan N, et al. Cerebral haemorrhage in a French prospective population study. J Neurol Neurosurg Psychiatry 1991;54:595–598.PubMedCrossRef
4.
Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med 1992;326:733–736.PubMedCrossRef
5.
Suzuki K, Kutsuzawa T, Takita K, et al. Clinico-epidemiologic study of stroke in Akita, Japan. Stroke 1987;18:402–406.PubMedCrossRef
6.
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;65:518–522.PubMedCrossRef
7.
Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project—1981-86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990;53:16–22.PubMedCrossRef
8.
Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007;115:e69-e171.PubMedCrossRef
9.
Diringer MN, Edwards DF. Admission to a neurologic/neurosurgical intensive care unit is associated with reduced mortality rate after intracerebral hemorrhage. Crit Care Med 2001;29:635–640.PubMedCrossRef
10.
Varelas PN, Schultz L, Conti M, Spanaki M, Genarrelli T, Hacein-Bey L. The impact of a neuro-intensivist on patients with stroke admitted to a neurosciences intensive care unit. Neurocrit Care 2008;9:293–299.PubMedCrossRef
11.
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006;5:53–63.PubMedCrossRef
12.
Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007;68:116–121.PubMedCrossRef
13.
Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004;164:880–884.PubMedCrossRef
14.
Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005;36:1588–1593.PubMedCrossRef
15.
Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 2007;50:309–315.PubMedCrossRef
16.
O'Donnell HC, Rosand J, Knudsen KA, et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000;342:240–245.PubMedCrossRef
17.
Greenberg SM, Vonsattel JP. Diagnosis of cerebral amyloid angiopathy. Sensitivity and specificity of cortical biopsy. Stroke 1997;28:1418–1422.PubMedCrossRef
18.
19.
Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP, Jr. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991;30:637–649.PubMedCrossRef
20.
Greenberg SM, Briggs ME, Hyman BT, et al. Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke 1996;27:1333–1337.PubMedCrossRef
21.
Nicoll JA, Burnett C, Love S, et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997;41:716–721.PubMedCrossRef
22.
Yamada M, Itoh Y, Suematsu N, Matsushita M, Otomo E. Lack of an association between apolipoprotein E epsilon 4 and cerebral amyloid angiopathy in elderly Japanese. Ann Neurol 1996;39:683–684.PubMedCrossRef
23.
Greenberg SM, Vonsattel JP, Segal AZ, et al. Association of apolipoprotein E epsilon2 and vasculopathy in cerebral amyloid angiopathy. Neurology 1998;50:961–965.PubMed
24.
Biffi A, Sonni A, Anderson CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 2010;68:934–943.PubMedCrossRef
25.
Biffi A, Kissela B, Ayres AM, et al. International Stroke Conference Oral Presentations: APOE Genotype Predicts Hematoma Volume and Expansion in Intracerebral Hemorrhage. Stroke 2011;42:e102.CrossRef
26.
Schmechel DE, Saunders AM, Strittmatter WJ, et al. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A 1993;90:9649–9653.PubMedCrossRef
27.
Gervais F, Chalifour R, Garceau D, et al. Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy. Amyloid 2001;8 Suppl 1:28–35.PubMed
28.
29.
Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006;354:1489–1496.PubMedCrossRef
30.
Gould DB, Phalan FC, Breedveld GJ, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005;308:1167–1171.PubMedCrossRef
31.
Volonghi I, Pezzini A, Del Zotto E, et al. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. The COL4A1 stroke syndrome. Curr Med Chem 2010;17:1317–1324.PubMedCrossRef
32.
Lanfranconi S, Markus HS. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke 2010;41:e513-518.PubMedCrossRef
33.
34.
Lanktree MB, Dichgans M, Hegele RA. Advances in genomic analysis of stroke: what have we learned and where are we headed? Stroke 2010;41:825–832.PubMedCrossRef
35.
Brown MB, Biffi A, Jeremiasz J, et al. International Stroke Conference and Nursing Symposium Poster Presentations: Genome Wide Association Study of Intracerebral Hemorrhage. Stroke 2011;42:e218.
36.
37.
Furlan AJ, Whisnant JP, Elveback LR. The decreasing incidence of primary intracerebral hemorrhage: a population study. Ann Neurol 1979;5:367–373.PubMedCrossRef
38.
Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke 2003;34:2060–2065.PubMedCrossRef
39.
SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255–3264.
40.
Mutlu N, Berry RG, Alpers BJ. Massive Cerebral Hemorrhage. Clinical and Pathological Correlations. Arch Neurol 1963;8:644–661.PubMed
41.
Broderick J, Brott T, Tomsick T, Leach A. Lobar hemorrhage in the elderly. The undiminishing importance of hypertension. Stroke 1993;24:49–51.PubMedCrossRef
42.
Charcot JM, Bouchard C. Nouvelles recherché sur la pathogenie de l’hemorragie cerebrale. Arch Physiol Norm Pathol 1868. 1: p. 110.
43.
Johansson BB. Vascular mechanisms in hypertensive cerebrovascular disease. J Cardiovasc Pharmacol 1992;(19 suppl 3):S11-S15.PubMed
44.
Ellis AG. The pathogenesis of spontaneous cerebral hemorrhage. Proc Pathol Soc (Phila) 1909;12:197.
45.
Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med 2001;344:1450–1460.PubMedCrossRef
46.
Fisher CM. Pathological observations in hypertensive cerebral hemorrhage. J Neuropathol Exp Neurol 1971;30:536–550.PubMedCrossRef
47.
Broderick JP, Brott TG, Tomsick T, Barsan W, Spilker J. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg 1990;72:195–199.PubMedCrossRef
48.
Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke 1996;27:1783–1787.PubMedCrossRef
49.
Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1–5.PubMedCrossRef
50.
Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Tanaka R. Multivariate analysis of predictors of hematoma enlargement in spontaneous intracerebral hemorrhage. Stroke 1998;29:1160–1166.PubMedCrossRef
51.
Jauch EC, Lindsell CJ, Adeoye O, et al. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage. Stroke 2006;37:2061–2065.PubMedCrossRef
52.
Fehr MA, Anderson DC. Incidence of progression or rebleeding in hypertensive intracerebral hemorrhage. J Stroke Cerebrovascular Dis 1991;1:111–116.
53.
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;36:86–91.PubMedCrossRef
54.
Davis SM, Broderick J, Hennerici M, et al. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006;66:1175–1181.PubMedCrossRef
55.
Mayer SA. Recombinant activated factor VII for acute intracerebral hemorrhage. Stroke 2007;38(2 suppl):763–767.PubMedCrossRef
56.
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.PubMedCrossRef
57.
Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score. Stroke 2009;40:2994–3000.PubMedCrossRef
58.
Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology 2007;68:889–894.PubMedCrossRef
59.
Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257–1262.PubMedCrossRef
60.
Hallevi H, Abraham AT, Barreto AD, Grotta JC, Savitz SI. The spot sign in intracerebral hemorrhage: the importance of looking for contrast extravasation. Cerebrovasc Dis 2010;29:217–220.PubMedCrossRef
61.
62.
Willmot M, Leonardi-Bee J, Bath PM. High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension 2004;43:18–24.PubMedCrossRef
63.
Zhang Y, Reilly KH, Tong W, et al. Blood pressure and clinical outcome among patients with acute stroke in Inner Mongolia, China. J Hypertens 2008;26:1446–1452.PubMedCrossRef
64.
Ohwaki K, Yano E, Nagashima H, Hirata M, Nakagomi T, Tamura A. Blood pressure management in acute intracerebral hemorrhage: relationship between elevated blood pressure and hematoma enlargement. Stroke 2004;35:1364–1367.PubMedCrossRef
65.
Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab 2001;21:804–810.PubMedCrossRef
66.
Anderson CS, Huang Y, Wang JG, et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol 2008;7:391–399.PubMedCrossRef
67.
68.
Qureshi AI. Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med 2010;38:637–648.CrossRef
69.
70.
Mayer SA, Sacco RL, Shi T, Mohr JP. Neurologic deterioration in noncomatose patients with supratentorial intracerebral hemorrhage. Neurology 1994;44:1379–1384.PubMed
71.
Qureshi AI, Suri MF, Ostrow PT, et al. Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery 2003;52:1041–1048.PubMedCrossRef
72.
Wu G, Xi G, Huang F. Spontaneous intracerebral hemorrhage in humans: hematoma enlargement, clot lysis, and brain edema. Acta Neurochir Suppl 2006;96:78–80.PubMedCrossRef
73.
Ruscalleda J, Peiro A. Prognostic factors in intraparenchymatous hematoma with ventricular hemorrhage. Neuroradiology 1986;28:34–37.PubMedCrossRef
74.
Welch KMA, Caplan LR, Reis DJ, Seisjo BK, B W, eds. Primer on Cerebrovascular Diseases. 1997, Academic Press.
75.
Xi G, Hua Y, Bhasin RR, Ennis SR, Keep RF, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of extravasated red blood cells on blood flow and blood-brain barrier integrity. Stroke 2001;32:2932–2938.PubMedCrossRef
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.PubMedCrossRef
77.
Rosenberg GA, Navratil M. Metalloproteinase inhibition blocks edema in intracerebral hemorrhage in the rat. Neurology 1997;48:921–926.PubMed
78.
Abilleira S, Montaner J, Molina CA, Monasterio J, Castillo J, Alvarez-Sabin J. Matrix metalloproteinase-9 concentration after spontaneous intracerebral hemorrhage. J Neurosurg 2003;99:65–70.PubMedCrossRef
79.
Makogonenko E, Tsurupa G, Ingham K, Medved L. Interaction of fibrin(ogen) with fibronectin: further characterization and localization of the fibronectin-binding site. Biochemistry 2002;41:7907–7913.PubMedCrossRef
80.
Hickenbottom SL, Grotta JC, Strong R, Denner LA, Aronowski J. Nuclear factor-kappaB and cell death after experimental intracerebral hemorrhage in rats. Stroke 1999;30:2472–2478.PubMedCrossRef
81.
Gong C, Boulis N, Qian J, Turner DE, Hoff JT, Keep RF. Intracerebral hemorrhage-induced neuronal death. Neurosurgery 2001;48:875–883.PubMed
82.
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.PubMed
83.
Hankey GJ, Hon C. Surgery for primary intracerebral hemorrhage: is it safe and effective? A systematic review of case series and randomized trials. Stroke 1997;28:2126–2132.PubMedCrossRef
84.
85.
Vespa P, McArthur D, Miller C, et al. Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduction of hemorrhage volume and neurological improvement. Neurocrit Care 2005;2:274–281.PubMedCrossRef
86.
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;96:177–182.PubMedCrossRef
87.
Mohr JP, Choi DW, Grotta JC, Weir B, PA W, eds. Stroke: Pathophysiology, Diagnosis, and Management. 1998, Churchill Livingstone.
88.
Findlay JM, Weir BK, Kanamaru K, et al. Intrathecal fibrinolytic therapy after subarachnoid hemorrhage: dosage study in a primate model and review of the literature. Can J Neurol Sci 1989;16:28–40.PubMed
89.
Morgan T, Awad I, Keyl P, Lane K, Hanley D. Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial. Acta Neurochir Suppl 2008;105:217–220.PubMedCrossRef
90.
Aronowski J, Hall CE. New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies. Neurol Res 2005;27:268–279.PubMedCrossRef
91.
Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci Lett 2000;283:230–232.PubMedCrossRef
92.
Cox G, Crossley J, Xing Z. Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am J Respir Cell Mol Biol 1995;12:232–237.PubMed
93.
Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 1999;160(5 pt 2):S5-S11.PubMed
94.
Batchelor PE, Liberatore GT, Wong JY, et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 1999;19:1708–1716.PubMed
95.
Lin TN, Cheung WM, Wu JS, et al. 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 2006;26:481–487.PubMedCrossRef
96.
Majno G. The Healing Hand: Man and Wound in the Ancient Word, 1975. Cambridge, MA: Harvard University Press.
97.
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;54:655–664.PubMedCrossRef
98.
Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG. Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke 2006;37:1087–1093.PubMedCrossRef
99.
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;81:93–102.PubMedCrossRef
100.
Hattori R, Inoue R, Sase K, et al. Preferential inhibition of inducible nitric oxide synthase by ebselen. Eur J Pharmacol 1994;267:R1-R2.PubMed
101.
Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 1998;89:991–996.PubMedCrossRef
102.
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.PubMedCrossRef
103.
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.PubMedCrossRef
104.
105.
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;24:926–933.PubMedCrossRef
106.
Park HK, Lee SH, Chu K, Roh JK. Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage. J Neurol Sci 2009;279(1–2):43–46.PubMedCrossRef
107.
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;36:326–331.PubMedCrossRef
108.
Zoellner H, Hofler M, Beckmann R, et al. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells. J Cell Sci 1996;109(pt 10):2571–2580.PubMed
109.
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.PubMedCrossRef
110.
111.
Zhao Z, Cheng M, Maples KR. et al. NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat. Brain Res 2001;909:46.PubMedCrossRef
112.
Sydserff SG, Borelli AR, Green AR, Cross AJ. Effect of NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window. Br J Pharmacol 2002;135:103–112.PubMedCrossRef
113.
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.PubMedCrossRef
114.
Saver JL, Albers GW, Dunn B, Johnston KC, Fisher M. Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke 2009;40:2594–2600.PubMedCrossRef
115.
Wu H, Wu T, Xu X, Wang J, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab 2010;31(5):1243–1250.PubMedCrossRef
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.PubMedCrossRef
117.
Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke 2009;40:1858–1863.PubMedCrossRef
118.
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.PubMedCrossRef
119.
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:ECP4.PubMedCrossRef
120.
121.
Selim M, Goldstein JN, Gomes J, et al. Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage: DFO in ICH Study. In International Stroke Conference, 2011. Los Angeles, CA.
122.
Sturgeon JD, Folsom AR, Longstreth WT, Jr., Shahar E, Rosamond WD, Cushman M. Risk factors for intracerebral hemorrhage in a pooled prospective study. Stroke 2007;38:2718–2725.PubMedCrossRef
123.
Orken DN, Kenangil G, Celik M, et al. Association of low cholesterol with primary intracerebral haemorrhage: a case control study. Acta Neurol Scand 2009;119:151–154.PubMedCrossRef
124.
Amarenco P, Bogousslavsky J, Callahan A, 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–559.PubMedCrossRef
125.
Sironi L, Cimino M, Guerrini U, et al. Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler Thromb Vasc Biol 2003;23:322–327.PubMedCrossRef
126.
Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M. Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res 2002;942(1–2):23–30.PubMedCrossRef
127.
Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 2001;32:980–986.PubMedCrossRef
128.
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;101:104–107.PubMedCrossRef
129.
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;35:1744–1749.PubMedCrossRef
130.
Karki K, Knight RA, Han Y, et al. Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage. Stroke 2009;40:3384–3389.PubMedCrossRef
131.
Zacco A, Togo J, Spence K, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect cortical neurons from excitotoxicity. J Neurosci 2003;23:11104–11111.PubMed
132.
Naval NS, Abdelhak TA, Urrunaga N, Zeballos P, Mirski MA, Carhuapoma JR. An association of prior statin use with decreased perihematomal edema. Neurocrit Care 2008;8:13–18.PubMedCrossRef
133.
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. Cen Eur Neurosurg 2009;70:15–20.PubMedCrossRef
134.
135.
Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006;37:129–133.PubMedCrossRef
136.
Toyoda K, Okada Y, Minematsu K, et al. Antiplatelet therapy contributes to acute deterioration of intracerebral hemorrhage. Neurology 2005;65:1000–1004.PubMedCrossRef
137.
Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke 2009;40:2398–2401.PubMedCrossRef
138.
Foerch C, Sitzer M, Steinmetz H, Neumann-Haefelin T. Pretreatment with antiplatelet agents is not independently associated with unfavorable outcome in intracerebral hemorrhage. Stroke 2006;37:2165–2167.PubMedCrossRef
139.
Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICH. Neurology 2009;72:1397–1402.PubMedCrossRef
140.
Thompson BB, Bejot Y, Caso V, et al. Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review. Neurology 2010;75:1333–1342.PubMedCrossRef
141.
Creutzfeldt CJ, Weinstein JR, Longstreth WT, Jr., Becker KJ, McPharlin TO, Tirschwell DL. Prior antiplatelet therapy, platelet infusion therapy, and outcome after intracerebral hemorrhage. J Stroke Cerebrovasc Dis 2009;18:221–228.PubMedCrossRef
142.
Illoh K, Lucke J, Illoh O. Intracerebral Hemorrhage Patients Who Receive Blood Products have Worse Outcomes. Stroke: Abstracts From the 2008 International Stroke Conference 2008;39:709.
143.
144.
145.
Poller L, Jespersen J, Ibrahim S. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:2673–2675.PubMed
146.
Flaherty ML, Tao H, Haverbusch M, et al. Warfarin use leads to larger intracerebral hematomas. Neurology 2008;71:1084–1089.PubMedCrossRef
147.
Morgenstern LB, Hemphill JC, 3rd, 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.PubMedCrossRef
148.
Kawai N, Kawanishi M, Okauchi M, Nagao S. Effects of hypothermia on thrombin-induced brain edema formation. Brain Res 2001;895:50–58.PubMedCrossRef
149.
MacLellan CL, Davies LM, Fingas MS, Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke 2006;37:1266–1270.PubMedCrossRef
150.
Wu J, Yang S, Hua Y, Liu W, Keep RF, Xi G. Minocycline attenuates brain edema, brain atrophy and neurological deficits after intracerebral hemorrhage. Acta Neurochir Suppl 2010;106:147–150.PubMedCrossRef
151.
Auriat AM, Colbourne F. Delayed rehabilitation lessens brain injury and improves recovery after intracerebral hemorrhage in rats. Brain Res 2009;1251:262–268.PubMedCrossRef
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.PubMedCrossRef
153.
Takamatsu Y, Ishida A, Hamakawa M, Tamakoshi K, Jung CG, Ishida K. Treadmill running improves motor function and alters dendritic morphology in the striatum after collagenase-induced intracerebral hemorrhage in rats. Brain Res 2010;1355:165–173.PubMedCrossRef
154.
Metadata
Title
Treatment Targets in Intracerebral Hemorrhage
Authors
Navdeep Sangha
Nicole R. Gonzales
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Neurotherapeutics / Issue 3/2011
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-011-0055-z

Other articles of this Issue 3/2011

Neurotherapeutics 3/2011 Go to the issue

Review

Investigational Therapies for Ischemic Stroke: Neuroprotection and Neurorecovery

Review

Treatment of Acute Ischemic Stroke: Beyond Thrombolysis and Supportive Care

Review

Treatment of Risk Factors to Prevent Stroke

Review

Prevention of Cardioembolic Stroke

Original Article

Ginsenoside Rd in Experimental Stroke: Superior Neuroprotective Efficacy with a Wide Therapeutic Window

Abstracts

Abstracts from the ASENT 14th Annual Meeting