The Reasearch Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, H3G 1A4, Canada,
Transl Stroke Res. 2012 Mar;3(1):164-72. doi: 10.1007/s12975-011-0124-y. Epub 2011 Nov 15.
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.
蛛网膜下腔出血 (SAH) 是一种破坏性疾病，也是社会的主要负担。尽管如此，药物治疗选择仍然有限。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 通常无法产生广泛的神经元丢失，而这种情况在人类中经常发生。我们报告了一种最近描述的大鼠血管内穿孔模型的改良方法，该方法在 SAH 后 72 小时产生了广泛的异质性梗死。在诱导 SAH 后 1 小时监测脑血流 (CBF)，并进行或不进行颅内压 (ICP) 测量。评估血液负荷量，并在 72 小时使用组织学染色、血脑屏障破裂评估和神经元存活和小胶质细胞激活的免疫荧光成像来量化脑损伤。结果表明，ICP 测量可加快 CBF 的恢复，从而可能减轻脑损伤。较大的蛛网膜下腔血液负荷量预示着更广泛的神经元损伤，这可以通过组织学和免疫组织化学技术的组合轻松量化。因此，对于 SAH 后神经保护策略的研究，本方案由于大的血液负荷量、高 ICP 和低 CBF，产生了可量化的、临床相关的、异质性的梗死模式。
