Skip to main content

Advertisement

SpringerLink
Log in

Assessing the Evolution of Intracranial Hematomas by using Animal Models: A Review of the Progress and the Challenges

  • Review Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Stroke has become the second leading cause of death in people aged higher than 60 years, with cancer being the first. Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Using imaging techniques to evaluate the evolution of intracranial hematomas in patients with hemorrhagic stroke is worthy of ongoing research. The difficulty in obtaining ultra-early imaging data and conducting intensive dynamic radiographic imaging in actual clinical settings has led to the application of experimental animal models to assess the evolution of intracranial hematomas. Herein, we review the current knowledge on primary intracerebral hemorrhage mechanisms, focus on the progress of animal studies related to hematoma development and secondary brain injury, introduce preclinical therapies, and summarize related challenges and future directions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

ICH:

Intracerebral hemorrhage

SICH:

Spontaneous intracerebral hemorrhage

BBB:

Blood–brain barrier

PARs:

Protease-activated receptors

IGF-1:

Insulin-like growth factor-1

CAA:

Cerebrovascular amyloidosis

RBCs:

Red blood cells

References

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

    Article  Google Scholar 

  • Andaluz N, Zuccarello M, Wagner KR (2002) Experimental animal models of intracerebral hemorrhage. Neurosurg Clin N Am 13:385–393

    Article  PubMed  Google Scholar 

  • Anderson CS, Chalmers J, Stapf C (2013) Blood-pressure lowering in acute intracerebral hemorrhage. N Engl J Med 369:1274–1275

    CAS  PubMed  Google Scholar 

  • Archie JP, Fixler DE, Ullyot DJ, Buckberg GD, Hoffman JI (1974) Regional myocardial blood flow in lambs with concentric right ventricular hypertrophy. Circ Res 34:143–154

    Article  CAS  PubMed  Google Scholar 

  • Aviv RI, Huynh T, Huang Y, Ramsay D, Van Slyke P, Dumont D, Asmah P, Alkins R, Liu R, Hynynen K (2014) An in vivo, MRI-integrated real-time model of active contrast extravasation in acute intracerebral hemorrhage. AJNR Am J Neuroradiol 35:1693–1699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai Q, Sheng Z, Liu Y, Zhang R, Yong VW, Xue M (2020a) Intracerebral haemorrhage: from clinical settings to animal models. Stroke Vasc Neurol 5:388–395

    Article  PubMed  PubMed Central  Google Scholar 

  • Bai Q, Xue M, Yong VW (2020b) Microglia and macrophage phenotypes in intracerebral haemorrhage injury: therapeutic opportunities. Brain 143:1297–1314

    Article  PubMed  Google Scholar 

  • Brouwers HB, Chang Y, Falcone GJ, Cai X, Ayres AM, Battey TW, Vashkevich A, McNamara KA, Valant V, Schwab K, Orzell SC, Bresette LM, Feske SK, Rost NS, Romero JM, Viswanathan A, Chou SH, Greenberg SM, Rosand J, Goldstein JN (2014) Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol 71:158–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Bullock R, Brock-Utne J, van Dellen J, Blake G (1988) Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow. Surg Neurol 29:101–107

    Article  CAS  PubMed  Google Scholar 

  • Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S (2004) Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke 35:1879–1885

    Article  PubMed  Google Scholar 

  • Cao S, Zheng M, Hua Y, Chen G, Keep RF, Xi G (2016) Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage. Stroke 47:1626–1631

    Article  PubMed  PubMed Central  Google Scholar 

  • Castaneda VS, Weinl C, Calaminus C, Wang L, Harant M, Ehrlichmann W, Thiele D, Kohlhofer U, Reischl G, Hempel JM, Ernemann U, Quintanilla ML, Nordheim A, Pichler BJ (2017) Characterization of a novel murine model for spontaneous hemorrhagic stroke using in vivo PET and MR multiparametric imaging. Neuroimage 155:245–256

    Article  Google Scholar 

  • Chang CF, Massey J, Osherov A, Angenendt DCL, Sansing LH (2020) Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage. Stroke 51:612–618

    Article  CAS  PubMed  Google Scholar 

  • Charidimou A, Kakar P, Fox Z, Werring DJ (2013) Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 44:995–1001

    Article  PubMed  Google Scholar 

  • Chen Q, Liu J, Xu H, He W, Li Y, Jiao L, Xiang Y, Zhan C, Chen J, Yang X, Huang S, Yang Y (2019) Association Between Eosinophilic Leukocyte Count and Hematoma Expansion in Acute Spontaneous Intracerebral Hemorrhage. Front Neurol 10:1164

    Article  PubMed  PubMed Central  Google Scholar 

  • Cho J, Park KS, Karki M, Lee E, Ko S, Kim JK, Lee D, Choe J, Son J, Kim M, Lee S, Lee J, Yoon C, Park S (2019) Improving Sensitivity on Identification and Delineation of Intracranial Hemorrhage Lesion Using Cascaded Deep Learning Models. J Digit Imaging 32:450–461

    Article  PubMed  PubMed Central  Google Scholar 

  • Chung PW, Kim JT, Sanossian N, Starkmann S, Hamilton S, Gornbein J, Conwit R, Eckstein M, Pratt F, Stratton S, Liebeskind DS, Saver JL (2018) Association Between Hyperacute Stage Blood Pressure Variability and Outcome in Patients With Spontaneous Intracerebral Hemorrhage. Stroke 49:348–354

    Article  PubMed  Google Scholar 

  • Dang G, Yang Y, Wu G, Hua Y, Keep RF, Xi G (2017) Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage. Transl Stroke Res 8:174–182

    Article  CAS  PubMed  Google Scholar 

  • Deinsberger W, Vogel J, Kuschinsky W, Auer LM, Boker DK (1996) Experimental intracerebral hemorrhage: description of a double injection model in rats. Neurol Res 18:475–477

    Article  CAS  PubMed  Google Scholar 

  • D’Esterre CD, Chia TL, Jairath A, Lee TY, Symons SP, Aviv RI (2011) Early rate of contrast extravasation in patients with intracerebral hemorrhage. AJNR Am J Neuroradiol 32:1879–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE (2011) Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology 76:1238–1244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edlow BL, Bove RM, Viswanathan A, Greenberg SM, Silverman SB (2012) The pattern and pace of hyperacute hemorrhage expansion. Neurocrit Care 17:250–254

    Article  PubMed  PubMed Central  Google Scholar 

  • Engler-Chiurazzi EB, Monaghan KL, Wan E, Ren X (2020) Role of B cells and the aging brain in stroke recovery and treatment. Geroscience 42:1199–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulop GA, Ramirez-Perez FI, Kiss T, Tarantini S, Valcarcel AM, Toth P, Yabluchanskiy A, Conley SM, Ballabh P, Martinez-Lemus LA, Ungvari Z, Csiszar A (2019) IGF-1 Deficiency Promotes Pathological Remodeling of Cerebral Arteries: A Potential Mechanism Contributing to the Pathogenesis of Intracerebral Hemorrhages in Aging. J Gerontol A Biol Sci Med Sci 74:446–454

    Article  CAS  PubMed  Google Scholar 

  • Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, Et A (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373:523–527

    Article  CAS  PubMed  Google Scholar 

  • Gao C, Meng Y, Chen G, Chen W, Chen XS, Luo CL, Zhang MY, Wang ZF, Wang T, Tao LY (2020) Chronic restraint stress exacerbates neurological deficits and disrupts the remodeling of the neurovascular unit in a mouse intracerebral hemorrhage model. Stress 23:338–348

    Article  CAS  PubMed  Google Scholar 

  • Gerhardson T, Sukovich JR, Chaudhary N, Chenevert TL, Ives K, Hall TL, Camelo-Piragua S, Xu Z, Pandey AS (2020) Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model. Neurosurgery 86:429–436

    Article  PubMed  Google Scholar 

  • Gong Y, Gong Y, Hou Z, Guo T, Deng J, Hao S, Wang B (2019) Establishment of an Experimental Intracerebral Haemorrhage Model for Mass Effect Research using a Thermo-sensitive Hydrogel. Sci Rep 9:13838

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo T, Ren P, Li X, Luo T, Gong Y, Hao S, Wang B (2018) Neural Injuries Induced by Hydrostatic Pressure Associated With Mass Effect after Intracerebral Hemorrhage. Sci Rep 8:9195

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gustafsson O, Rossitti S, Ericsson A, Raininko R (1999) MR imaging of experimentally induced intracranial hemorrhage in rabbits during the first 6 hours. Acta Radiol 40:360–368

    Article  CAS  PubMed  Google Scholar 

  • Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, Lane K, McBee N, Mayo SW, Bistran-Hall AJ, Gandhi D, Mould WA, Ullman N, Ali H, Carhuapoma JR, Kase CS, Lees KR, Dawson J, Wilson A, Betz JF, Sugar EA, Hao Y, Avadhani R, Caron JL, Harrigan MR, Carlson AP, Bulters D, LeDoux D, Huang J, Cobb C, Gupta G, Kitagawa R, Chicoine MR, Patel H, Dodd R, Camarata PJ, Wolfe S, Stadnik A, Money PL, Mitchell P, Sarabia R, Harnof S, Barzo P, Unterberg A, Teitelbaum JS, Wang W, Anderson CS, Mendelow AD, Gregson B, Janis S, Vespa P, Ziai W, Zuccarello M, Awad IA (2019) Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 393:1021–1032

    PubMed  PubMed Central  Google Scholar 

  • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102

    Article  CAS  PubMed  Google Scholar 

  • Hu L, Zhang H, Wang B, Ao Q, He Z (2020) MicroRNA-152 attenuates neuroinflammation in intracerebral hemorrhage by inhibiting thioredoxin interacting protein (TXNIP)-mediated NLRP3 inflammasome activation. Int Immunopharmacol 80:106141

    Article  CAS  PubMed  Google Scholar 

  • Iida S, Baumbach GL, Lavoie JL, Faraci FM, Sigmund CD, Heistad DD (2005) Spontaneous stroke in a genetic model of hypertension in mice. Stroke 36:1253–1258

    Article  PubMed  Google Scholar 

  • Illanes S, Zhou W, Heiland S, Markus Z, Veltkamp R (2010) Kinetics of hematoma expansion in murine warfarin-associated intracerebral hemorrhage. Brain Res 1320:135–142

    Article  CAS  PubMed  Google Scholar 

  • Jakel L, Van Nostrand WE, Nicoll J, Werring DJ, Verbeek MM (2017) Animal models of cerebral amyloid angiopathy. Clin Sci (lond) 131:2469–2488

    Article  CAS  Google Scholar 

  • Jing C, Bian L, Wang M, Keep RF, Xi G, Hua Y (2019) Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage. Stroke 50:1539–1547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnston SC, Mendis S, Mathers CD (2009) Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol 8:345–354

    Article  PubMed  Google Scholar 

  • Jung JE, Sun G, Bautista GJ, Obertas L, Mobley AS, Ting SM, Zhao X, Aronowski J (2020) The Mitochondria-Derived Peptide Humanin Improves Recovery from Intracerebral Hemorrhage: Implication of Mitochondria Transfer and Microglia Phenotype Change. J Neurosci 40:2154–2165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T (1996) Enlargement of spontaneous intracerebral hemorrhage. Incidence and Time Course Stroke 27:1783–1787

    CAS  PubMed  Google Scholar 

  • Lau KK, Wong YK, Teo KC, Chang R, Tse MY, Hoi CP, Chan CY, Chan OL, Cheung R, Wong E, Kwan J, Hui ES, Mak H (2017) Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke. J Am Heart Assoc 6

  • Lee EJ, Hung YC, Lee MY (1999) Anemic hypoxia in moderate intracerebral hemorrhage: the alterations of cerebral hemodynamics and brain metabolism. J Neurol Sci 164:117–123

    Article  CAS  PubMed  Google Scholar 

  • Lee KR, Betz AL, Kim S, Keep RF, Hoff JT (1996) The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage. Acta Neurochir (Wien) 138:396–400; discussion 400–1

    Article  CAS  Google Scholar 

  • Li N, Liu YF, Ma L, Worthmann H, Wang YL, Wang YJ, Gao YP, Raab P, Dengler R, Weissenborn K, Zhao XQ (2013) Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage. Stroke 44:658–663

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Yin Q, Zhong Q, Lv FL, Zhou Y, Li JQ, Wang JZ, Su BY, Yang QW (2012) Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. J Neuroinflammation 9:46

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Gao BB, Clermont AC, Blair P, Chilcote TJ, Sinha S, Flaumenhaft R, Feener EP (2011) Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med 17:206–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu R, Huynh TJ, Huang Y, Ramsay D, Hynynen K, Aviv RI (2015) Modeling the pattern of contrast extravasation in acute intracerebral hemorrhage using dynamic contrast-enhanced MR. Neurocrit Care 22:320–324

    Article  CAS  PubMed  Google Scholar 

  • Ma Q, Manaenko A, Khatibi NH, Chen W, Zhang JH, Tang J (2011) Vascular adhesion protein-1 inhibition provides antiinflammatory protection after an intracerebral hemorrhagic stroke in mice. J Cereb Blood Flow Metab 31:881–893

    Article  CAS  PubMed  Google Scholar 

  • Mao LL, Yuan H, Wang WW, Wang YJ, Yang MF, Sun BL, Zhang ZY, Yang XY (2017) Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage. Cell Mol Neurobiol 37:919–929

    Article  CAS  PubMed  Google Scholar 

  • Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (2008) Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 358:2127–2137

    Article  CAS  PubMed  Google Scholar 

  • Morotti A, Busto G, Scola E, Carlesi E, Di Pasquale F, Casetta I, Fainardi E (2021) Association between perihematomal perfusion and intracerebral hemorrhage shape. Neuroradiology

  • Morotti A, Charidimou A, Phuah CL, Jessel MJ, Schwab K, Ayres AM, Romero JM, Viswanathan A, Gurol ME, Greenberg SM, Anderson CD, Rosand J, Goldstein JN (2016) Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage. JAMA Neurol 73:1285–1290

    Article  PubMed  PubMed Central  Google Scholar 

  • Nishimura N, Schaffer CB, Friedman B, Tsai PS, Lyden PD, Kleinfeld D (2006) Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat Methods 3:99–108

    Article  CAS  PubMed  Google Scholar 

  • Nyul-Toth A, Tarantini S, Kiss T, Toth P, Galvan V, Tarantini A, Yabluchanskiy A, Csiszar A, Ungvari Z (2020) Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer’s disease. Geroscience 42:1685–1698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldenborg PA, Zheleznyak A, Fang YF, Lagenaur CF, Gresham HD, Lindberg FP (2000) Role of CD47 as a marker of self on red blood cells. Science 288:2051–2054

    Article  CAS  PubMed  Google Scholar 

  • Orakcioglu B, Becker K, Sakowitz OW, Herweh C, Kohrmann M, Huttner HB, Steiner T, Unterberg A, Schellinger PD (2008) MRI of the perihemorrhagic zone in a rat ICH model: effect of hematoma evacuation. Neurocrit Care 8:448–455

    Article  PubMed  Google Scholar 

  • Orakcioglu B, Fiebach JB, Steiner T, Kollmar R, Juttler E, Becker K, Schwab S, Heiland S, Meyding-Lamade UK, Schellinger PD (2005) Evolution of early perihemorrhagic changes–ischemia vs. edema: an MRI study in rats. Exp Neurol 193:369–376

    Article  CAS  PubMed  Google Scholar 

  • Qureshi AI, Ling GS, Khan J, Suri MF, Miskolczi L, Guterman LR, Hopkins LN (2001) Quantitative analysis of injured, necrotic, and apoptotic cells in a new experimental model of intracerebral hemorrhage. Crit Care Med 29:152–157

    Article  CAS  PubMed  Google Scholar 

  • Revesz T, Holton JL, Lashley T, Plant G, Rostagno A, Ghiso J, Frangione B (2002) Sporadic and familial cerebral amyloid angiopathies. Brain Pathol 12:343–357

    Article  PubMed  Google Scholar 

  • Ropper AH, Zervas NT (1982) Cerebral blood flow after experimental basal ganglia hemorrhage. Ann Neurol 11:266–271

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M (1990) Collagenase-induced intracerebral hemorrhage in rats. Stroke 21:801–807

    Article  CAS  PubMed  Google Scholar 

  • Russell RW (1975) How does blood-pressure cause stroke? Lancet 2:1283–1285

    Article  CAS  PubMed  Google Scholar 

  • Rynkowski MA, Kim GH, Komotar RJ, Otten ML, Ducruet AF, Zacharia BE, Kellner CP, Hahn DK, Merkow MB, Garrett MC, Starke RM, Cho BM, Sosunov SA, Connolly ES (2008) A mouse model of intracerebral hemorrhage using autologous blood infusion. Nat Protoc 3:122–128

    Article  CAS  PubMed  Google Scholar 

  • Savonenko A, Xu GM, Melnikova T, Morton JL, Gonzales V, Wong MP, Price DL, Tang F, Markowska AL, Borchelt DR (2005) Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer’s disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis 18:602–617

    Article  CAS  PubMed  Google Scholar 

  • Schallner N, Pandit R, LeBlanc RR, Thomas AJ, Ogilvy CS, Zuckerbraun BS, Gallo D, Otterbein LE, Hanafy KA (2015) Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1. J Clin Invest 125:2609–2625

    Article  PubMed  PubMed Central  Google Scholar 

  • Schellinger PD, Fiebach JB, Hoffmann K, Becker K, Orakcioglu B, Kollmar R, Juttler E, Schramm P, Schwab S, Sartor K, Hacke W (2003) Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra? Stroke 34:1674–1679

    Article  PubMed  Google Scholar 

  • Schindlbeck KA, Santaella A, Galinovic I, Krause T, Rocco A, Nolte CH, Villringer K, Fiebach JB (2016) Spot Sign in Acute Intracerebral Hemorrhage in Dynamic T1-Weighted Magnetic Resonance Imaging. Stroke 47:417–423

    Article  PubMed  Google Scholar 

  • Schlunk F, Greenberg SM (2015) The Pathophysiology of Intracerebral Hemorrhage Formation and Expansion. Transl Stroke Res 6:257–263

    Article  CAS  PubMed  Google Scholar 

  • Selim M, Sheth KN (2015) Perihematoma edema: a potential translational target in intracerebral hemorrhage? Transl Stroke Res 6:104–106

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi E, Shi K, Qiu S, Sheth KN, Lawton MT, Ducruet AF (2019) Chronic inflammation, cognitive impairment, and distal brain region alteration following intracerebral hemorrhage. FASEB J 33:9616–9626

    Article  CAS  PubMed  Google Scholar 

  • Sinar EJ, Mendelow AD, Graham DI, Teasdale GM (1987) Experimental intracerebral hemorrhage: effects of a temporary mass lesion. J Neurosurg 66:568–576

    Article  CAS  PubMed  Google Scholar 

  • Sorimachi T, Fujii Y, Morita K, Tanaka R (2007) Predictors of hematoma enlargement in patients with intracerebral hemorrhage treated with rapid administration of antifibrinolytic agents and strict blood pressure control. J Neurosurg 106:250–254

    Article  CAS  PubMed  Google Scholar 

  • Sprugel MI, Kuramatsu JB, Volbers B, Gerner ST, Sembill JA, Madzar D, Bobinger T, Kolbl K, Hoelter P, Lucking H, Dorfler A, Schwab S, Huttner HB (2019) Perihemorrhagic edema: Revisiting hematoma volume, location, and surface. Neurology 93:e1159–e1170

    Article  PubMed  Google Scholar 

  • Staykov D, Wagner I, Volbers B, Hauer EM, Doerfler A, Schwab S, Bardutzky J (2011) Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke 42:2625–2629

    Article  PubMed  Google Scholar 

  • Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, Waridel C, Calhoun ME, Jucker M, Probst A, Staufenbiel M, Sommer B (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 94:13287–13292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sudduth TL, Powell DK, Smith CD, Greenstein A, Wilcock DM (2013) Induction of hyperhomocysteinemia models vascular dementia by induction of cerebral microhemorrhages and neuroinflammation. J Cereb Blood Flow Metab 33:708–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sumbria RK, Grigoryan MM, Vasilevko V, Krasieva TB, Scadeng M, Dvornikova AK, Paganini-Hill A, Kim R, Cribbs DH, Fisher MJ (2016) A murine model of inflammation-induced cerebral microbleeds. J Neuroinflammation 13:218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takasugi S, Ueda S, Matsumoto K (1985) Chronological changes in spontaneous intracerebral hematoma–an experimental and clinical study. Stroke 16:651–658

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Marumo T, Shibuta H, Omura T, Yoshida S (2009) Serum S100B, brain edema, and hematoma formation in a rat model of collagenase-induced hemorrhagic stroke. Brain Res Bull 78:158–163

    Article  CAS  PubMed  Google Scholar 

  • Tarantini S, Tucsek Z, Valcarcel-Ares MN, Toth P, Gautam T, Giles CB, Ballabh P, Wei JY, Wren JD, Ashpole NM, Sonntag WE, Ungvari Z, Csiszar A (2016) Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging. Age (dordr) 38:273–289

    Article  CAS  Google Scholar 

  • Taylor RA, Sansing LH (2013) Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol 2013:746068

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tong LS, Shao AW, Ou YB, Guo ZN, Manaenko A, Dixon BJ, Tang J, Lou M, Zhang JH (2017) Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model. J Cereb Blood Flow Metab 37:1971–1981

    Article  CAS  PubMed  Google Scholar 

  • Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ (2020) Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets. J Stroke 22:29–46

    Article  PubMed  PubMed Central  Google Scholar 

  • Urday S, Kimberly WT, Beslow LA, Vortmeyer AO, Selim MH, Rosand J, Simard JM, Sheth KN (2015) Targeting secondary injury in intracerebral haemorrhage–perihaematomal oedema. Nat Rev Neurol 11:111–122

    Article  PubMed  Google Scholar 

  • van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ (2010) 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 9:167–176

    Article  PubMed  Google Scholar 

  • Wagner KR, Xi G, Hua Y, Kleinholz M, de Courten-Myers GM, Myers RE, Broderick JP, Brott TG (1996) Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter. Stroke 27:490–497

    Article  CAS  PubMed  Google Scholar 

  • Wan Y, Gao F, Ye F, Yang W, Hua Y, Keep RF, Xi G (2020) Effects of aging on hydrocephalus after intraventricular hemorrhage. Fluids Barriers CNS 17:8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J (2010) Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol 92:463–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang KY, Wu CH, Zhou LY, Yan XH, Yang RL, Liao LM, Ge XM, Liao YS, Li SJ, Li HZ, Gao LL, Lin JS, Huang SY (2015) Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage. Eur Neurol 74:28–35

    Article  PubMed  Google Scholar 

  • Wang S, Yao Q, Wan Y, Wang J, Huang C, Li D, Yang B (2020) Adiponectin reduces brain injury after intracerebral hemorrhage by reducing NLRP3 inflammasome expression. Int J Neurosci 130:301–308

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Chen Q, Tan Q, Feng Z, He Z, Tang J, Feng H, Zhu G, Chen Z (2018a) Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPARgamma-dependent manner. Neuropharmacology 128:244–254

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Li Z, Zhao X, Wang D, Li H, Xian Y, Liu L, Wang Y (2017) Stroke care quality in China: Substantial improvement, and a huge challenge and opportunity. Int J Stroke 12:229–235

    Article  PubMed  Google Scholar 

  • Wang YC, Zhou Y, Fang H, Lin S, Wang PF, Xiong RP, Chen J, Xiong XY, Lv FL, Liang QL, Yang QW (2014) Toll-like receptor 2/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage. Ann Neurol 75:876–889

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, Shen H, Chen G (2018b) Melatonin Alleviates Intracerebral Hemorrhage-Induced Secondary Brain Injury in Rats via Suppressing Apoptosis, Inflammation, Oxidative Stress, DNA Damage, and Mitochondria Injury. Transl Stroke Res 9:74–91

    Article  CAS  PubMed  Google Scholar 

  • Wei CC, Kong YY, Li GQ, Guan YF, Wang P, Miao CY (2017) Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci Rep 7:717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu TY, Sharma G, Strbian D, Putaala J, Desmond PM, Tatlisumak T, Davis SM, Meretoja A (2017) Natural History of Perihematomal Edema and Impact on Outcome After Intracerebral Hemorrhage. Stroke 48:873–879

    Article  PubMed  Google Scholar 

  • Wu X, Yan J, Ye H, Qiu J, Wang J, Wang Y (2020) Pre-treatment cerebral microbleeds and intracranial hemorrhage in patients with ischemic stroke receiving endovascular therapy: a systematic review and meta-analysis. J Neurol 267:1227–1232

    Article  PubMed  Google Scholar 

  • Xie WJ, Yu HQ, Zhang Y, Liu Q, Meng HM (2016) CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage. Neural Regen Res 11:1122–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Qiu GP, Huang J, Zhang B, Sun SQ, Gan SW, Lu WT, Wang KJ, Huang SQ, Zhu SJ (2015) Internalization of aquaporin-4 after collagenase-induced intracerebral hemorrhage. Anat Rec (hoboken) 298:554–561

    Article  CAS  Google Scholar 

  • Xue M, Balasubramaniam J, Buist RJ, Peeling J, Del BM (2003) Periventricular/intraventricular hemorrhage in neonatal mouse cerebrum. J Neuropathol Exp Neurol 62:1154–1165

    Article  PubMed  Google Scholar 

  • Xue M, Yong VW (2020) Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation. Lancet Neurol 19:1023–1032

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Zazulia AR, Diringer MN, Videen TO, Adams RE, Yundt K, Aiyagari V, Grubb RJ, Powers WJ (2001) Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab 21:804–810

    Article  CAS  PubMed  Google Scholar 

  • Zeng Z, Gong X, Hu Z (2020) L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model. Aging (Albany NY) 12:11768–11780

    Article  CAS  Google Scholar 

  • Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, Grotta JC, Aronowski J (2007) Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol 61:352–362

    Article  CAS  PubMed  Google Scholar 

  • Ziai WC (2013) Hematology and inflammatory signaling of intracerebral hemorrhage. Stroke 44:S74–S78

    Article  PubMed  Google Scholar 

  • Zille M, Karuppagounder SS, Chen Y, Gough PJ, Bertin J, Finger J, Milner TA, Jonas EA, Ratan RR (2017) Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis. Stroke 48:1033–1043

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Yihao Chen, Jianbo Chang, Junji Wei, Ming Feng & Renzhi Wang

Authors
  1. Yihao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianbo Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junji Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Renzhi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Chen and Wang conceived the study, while Chen and Chang analyzed and interpreted the experimental ICH data. Chen and Chang contributed equally to this work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Renzhi Wang.

Ethics declarations

Informed consent

For this study, formal consent was not required.

Research involving human participants and/or animals

This article does not contain any studies with human and animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Chang, J., Wei, J. et al. Assessing the Evolution of Intracranial Hematomas by using Animal Models: A Review of the Progress and the Challenges. Metab Brain Dis 36, 2205–2214 (2021). https://doi.org/10.1007/s11011-021-00828-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-021-00828-y

Keywords

Search

Navigation