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Standardized induction of subarachnoid hemorrhage in mice by intracranial pressure monitoring.

机译:通过颅内压监测标准化诱导小鼠蛛网膜下腔出血。

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BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is the subtype of stroke with the most unfavorable outcome but the least well investigated molecular pathophysiology. Among others, not sufficiently well standardized in vivo models suitable for the use with transgenic animals may be responsible for this situation. Therefore the aim of the current study was to detect suitable intra-operative parameters for the controlled and standardized induction of SAH in mice and to characterize the long-term functional and histopathological outcome of mice subjected to this procedure. METHODS: Experimental study in mice using the intraluminal Circle of Willis perforation (CWp) model of SAH. RESULTS: SAH induced a sharp increase of intracranial pressure (ICP) from 5.1+/-1.2 to 78.5+/-9.3 mm Hg (mean+/-SD; p<0.05), a concomitant drop of cerebral blood flow (rCBF) by 81+/-4% (p<0.05), and a significant Cushing reflex response (p<0.05). rCBF measurements alone could not reliably detect SAH. SAH resulted in significant brain edema formation (brain water content increase at 72 h: 2.9+/-0.9%; p<0.05), loss of hippocampal neurons (CA1: -56%, CA2: -55%; CA3: -72%; 7 days; p<0.05), severe neurological dysfunction over 7 days, and a mortality of 30%. CONCLUSIONS: Our results indicate that CWp in mice can be standardized by intra-operative ICP monitoring. CWp leads to prolonged intracranial hypertension, selective neuronal cell death in the hippocampus, and severe neurological dysfunction. CWp in mice with ICP monitoring may therefore become a valuable tool for future investigations of the molecular pathophysiology of SAH.
机译:背景与目的:蛛网膜下腔出血(SAH)是卒中的亚型,其结果最不利,但分子病理生理学研究最少。其中,没有足够好的标准化的适用于转基因动物的体内模型可能是造成这种情况的原因。因此,本研究的目的是为小鼠中SAH的受控和标准化诱导检测合适的术中参数,并表征接受该程序的小鼠的长期功能和组织病理学结果。方法:使用SAH的腔内Willis穿孔环(CWp)模型在小鼠中进行实验研究。结果:SAH引起的颅内压(ICP)从5.1 +/- 1.2急剧增加到78.5 +/- 9.3 mm Hg(平均+/- SD; p <0.05),同时脑血流量(rCBF)降低了81 +/- 4%(p <0.05)和显着的库欣反射反应(p <0.05)。仅凭rCBF测量无法可靠地检测出SAH。 SAH导致明显的脑水肿形成(72 h时脑水含量增加:2.9 +/- 0.9%; p <0.05),海马神经元丢失(CA1:-56%,CA2:-55%; CA3:-72% ; 7天; p <0.05),超过7天的严重神经功能障碍,死亡率为30%。结论:我们的结果表明,可以通过术中ICP监测对小鼠的CWp进行标准化。 CWp导致长时间的颅内高压,海马中选择性神经元细胞死亡以及严重的神经功能障碍。因此,具有ICP监测的小鼠CWp可能成为将来研究SAH分子病理生理学的有价值的工具。

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