An Endovascular Perforation Model of Subarachnoid Haemorrhage in Rat Produces Heterogeneous Infarcts that Increase with Blood Load
An Endovascular Perforation Model of Subarachnoid Haemorrhage in Rat Produces Heterogeneous Infarcts that Increase with Blood Load
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DOI：
10.1007/s12975-011-0124-y
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发表时间：
2012-03-01
影响因子：
6.9
通讯作者：
Allan, S. M.
中科院分区：
文献类型：
--
作者：
Greenhalgh, A. D.;Rothwell, N. J.;Allan, S. M.
蛛网膜下腔出血（SAH）是一种毁灭性的疾病，也是社会的主要负担。尽管如此，药物治疗选择有限。适当的SAH动物模型对于神经保护药物的开发至关重要，但实验性SAH通常不能产生广泛的神经元损失，如在人类中常见的那样。我们报告，最近描述的修改血管内穿孔模型在大鼠SAH后72小时产生广泛的异质性梗死。在诱导SAH后1 h监测脑血流量（CBF），伴或不伴颅内压（ICP）测量。评估血液负荷大小，并在72小时时使用组织学染色、血脑屏障破坏评估和神经元活力和小胶质细胞活化的免疫荧光成像来量化脑损伤。结果表明，ICP测量允许更快地恢复CBF，可能减少脑损伤。较大的蛛网膜下腔血负荷预测更广泛的神经元损伤，这是很容易量化与组织学和免疫组化技术相结合。因此，为了研究SAH后的神经保护策略，本方案产生了可量化的、临床相关的、由于大血负荷、高ICP和低CBF引起的异质性梗死模式。
Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on society. Despite this, pharmacological treatment options are limited. Appropriate animal modelling of SAH is essential for the development of neuroprotective drugs, but experimental SAH often fails to produce widespread neuronal loss, as frequently seen in humans. We report that a recently described modification of the endovascular perforation model in rat produced widespread heterogeneous infarcts 72 h after SAH. Cerebral blood flow (CBF) was monitored, with or without intracranial pressure (ICP) measurement, for 1 h after induction of SAH. Blood load size was assessed, and brain injury was quantified at 72 h using histological staining, blood brain barrier breakdown assessment and immunofluorescent imaging of neuronal viability and microglial activation. Results showed that ICP measurement allowed for faster recovery of CBF, potentially reducing brain injury. Larger subarachnoid blood loads predicted more extensive neuronal damage which was easily quantified with the combination of histological and immunohistochemical techniques. Thus, for the investigation of neuroprotective strategies after SAH, the present protocol produces quantifiable, clinically relevant, heterogeneous patterns of infarct due to large blood loads, high ICP and low CBF.