Abstract
Primary spontaneous intracerebral hemorrhage (ICH) with secondary intraventricular hemorrhage (IVH) is an important clinical problem of which little is known. IVH and hydrocephalus are independent predictors of poor outcome in ICH. The aims of this study were, therefore, to establish a rat model of ICH with ventricular extension and investigate the occurrence of post-hemorrhagic chronic hydrocephalus and perihematomal tissue injury. Based on our previous rat model of IVH, we adjusted the injection coordinates and 200 μl autologous blood was stereotaxically infused into the right striatum (coordinates: 0.2 mm posterior, 2.2 mm lateral, and 5.0 mm depth to the bregma). At 24 h post-infusion, the rats produced reproducible hematoma and ventricle expansion, which closely mimics the ICH with ventricular extension in humans. Hematoma consequences and perihematomal tissue injury were evaluated on the acute phase. At 4 weeks, ventricular dilatation, brain tissue loss, hippocampus volume, and cortical thickness were measured with magnetic resonance imaging and neurocognitive function was assessed using the Morris water maze test. With blood infusion, the animals demonstrated brain edema, blood–brain barrier breakdown, and marked perihematomal tissue injury on the acute phase. At 4 weeks, the T2 images showed remarkable hydrocephalus and tissue loss, and the Morris water maze test revealed neurocognitive deficits. The present ICH with the ventricular extension rat model features characteristics of both ICH and IVH rat models, which could be used for extending our pathophysiological understanding of post-hemorrhagic chronic hydrocephalus and perihematomal tissue damage.
Similar content being viewed by others
References
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31. doi:10.1016/S1474-4422(12)70104-7.
Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010;92(4):463–77. doi:10.1016/j.pneurobio.2010.08.001.
Bhattathiri PS, Gregson B, Prasad KS, Mendelow AD, Investigators S. Intraventricular hemorrhage and hydrocephalus after spontaneous intracerebral hemorrhage: results from the STICH trial. Acta Neurochir Suppl. 2006;96:65–8.
Hwang BY, Bruce SS, Appelboom G, Piazza MA, Carpenter AM, Gigante PR, et al. Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage. J Neurosurg. 2012;116(1):185–92. doi:10.3171/2011.9.JNS10850.
Hallevi H, Albright KC, Aronowski J, Barreto AD, Martin-Schild S, Khaja AM, et al. Intraventricular hemorrhage: anatomic relationships and clinical implications. Neurology. 2008;70(11):848–52. doi:10.1212/01.wnl.0000304930.47751.75.
Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, 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. doi:10.1016/S0140-6736(05)17826-X.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005;352(8):777–85. doi:10.1056/NEJMoa042991.
Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G. Role of iron in brain injury after intraventricular hemorrhage. Stroke. 2011;42(2):465–70. doi:10.1161/STROKEAHA.110.602755.
Strahle J, Garton HJ, Maher CO, Muraszko KM, Keep RF, Xi G. Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage. Transl Stroke Res. 2012;3 Suppl 1:25–38. doi:10.1007/s12975-012-0182-9.
MacLellan CL, Silasi G, Poon CC, Edmundson CL, Buist R, Peeling J, et al. Intracerebral hemorrhage models in rat: comparing collagenase to blood infusion. J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab. 2008;28(3):516–25. doi:10.1038/sj.jcbfm.9600548.
Chen Z, Zhang J, Chen Q, Guo J, Zhu G, Feng H. Neuroprotective effects of edaravone after intraventricular hemorrhage in rats. 2014;25(9):635–40. doi:10.1097/WNR.0000000000000050.
Manaenko A, Chen H, Kammer J, Zhang JH, Tang J. Comparison Evans Blue injection routes: intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model. J Neurosci Methods. 2011;195(2):206–10. doi:10.1016/j.jneumeth.2010.12.013.
Hatakeyama T, Okauchi M, Hua Y, Keep RF, Xi G. Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats. Transl Stroke Res. 2013;4(5):546–53. doi:10.1007/s12975-013-0270-5.
Jin H, Xi G, Keep RF, Wu J, Hua Y. DARPP-32 to quantify intracerebral hemorrhage-induced neuronal death in basal ganglia. Transl Stroke Res. 2013;4(1):130–4. doi:10.1007/s12975-012-0232-3.
Gao F, Liu F, Chen Z, Hua Y, Keep RF, Xi G. Hydrocephalus after intraventricular hemorrhage: the role of thrombin. J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab. 2014;34(3):489–94. doi:10.1038/jcbfm.2013.225.
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2006;1(2):848–58. doi:10.1038/nprot.2006.116.
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63. doi:10.1016/S1474-4422(05)70283-0.
Khatibi NH, Ma Q, Rolland W, Ostrowski R, Fathali N, Martin R, et al. Isoflurane posttreatment reduces brain injury after an intracerebral hemorrhagic stroke in mice. Anesth Analg. 2011;113(2):343–8. doi:10.1213/ANE.0b013e31821f9524.
Lekic T, Tang J, Zhang JH. Rat model of intracerebellar hemorrhage. Acta Neurochir Suppl. 2008;105:131–4.
MacLellan CL, Langdon KD, Churchill KP, Granter-Button S, Corbett D. Assessing cognitive function after intracerebral hemorrhage in rats. Behav Brain Res. 2009;198(2):321–8. doi:10.1016/j.bbr.2008.11.004.
Xi G, Strahle J, Hua Y, Keep RF. Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol. 2014;115:45–63. doi:10.1016/j.pneurobio.2013.09.007.
Acknowledgments
We would like to thank Dr. Ya Hua from the University of Michigan for her professional comments on this research. This work was supported by grants 81070929 (Z.C) and 81271281 (Z.C) from the National Natural Science Foundation of China and 2014CB541606 (H.F) from the National Key Basic Research Development Program (973 Program) of China.
Conflict of Interest
Qianwei Chen, Jianbo Zhang, Jing Guo, Jun Tang, Yihao Tao, Lin li, Hua Feng, and Zhi Chen declare that they have no conflict of interest.
Compliance with Ethics Requirements
All institutional and national guidelines for the care and use of laboratory animals were followed.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, Q., Zhang, J., Guo, J. et al. Chronic Hydrocephalus and Perihematomal Tissue Injury Developed in a Rat Model of Intracerebral Hemorrhage with Ventricular Extension. Transl. Stroke Res. 6, 125–132 (2015). https://doi.org/10.1007/s12975-014-0367-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12975-014-0367-5