Hua Ya, Schallert Timothy, Keep Richard F, Wu Jimin, Hoff Julian T, Xi Guohua
Department of Neurosurgery, University of Michigan, Ann Arbor 48109-0532, USA.
Stroke. 2002 Oct;33(10):2478-84. doi: 10.1161/01.str.0000032302.91894.0f.
In humans, intracerebral hemorrhage (ICH) causes marked perihematomal edema formation and neurological deficits. A rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of edema formation, but an examination of behavioral outcome would improve its preclinical utility and provide a more rigorous assessment of the pathological cascade of events over time. The purpose of this study was to use a battery of sensorimotor function tests to examine the neurological effects of ICH in the rat and to examine which components of the hematoma are involved in generating those effects.
The behavioral tests used were forelimb placing, preference for forelimb use for weight shifts during vertical exploration of a cylindrical enclosure, and a corner turn test. Rats were tested from day 1 to day 28 after injection of autologous whole blood; injection of blood plus hirudin (thrombin inhibitor), packed red blood cells, thrombin, or saline; or needle placement only.
The battery of tests indicated that there were marked neurological deficits by day 1 after ICH, with progressive recovery of function over 4 weeks. The forelimb placing score paralleled changes in edema. Injection of thrombin caused and injection of hirudin reduced the ICH-induced neurological deficits. Injection of packed red blood cells, which causes delayed edema formation, induced delayed neurological deficits
These tests allow continuous monitoring of neurological deficits after rat ICH and assessment of therapeutic interventions. The time course of the neurological deficit closely matched the time course of cerebral edema for both ICH and injection of blood components. There was marked recovery of function after ICH, which may be amenable to therapeutic manipulation.
在人类中，脑出血（ICH）会导致明显的血肿周围水肿形成和神经功能缺损。一种大鼠脑出血模型，即将自体血液注入尾状核，已被广泛用于研究水肿形成机制，但对行为结果的检查将提高其临床前效用，并能更严格地评估随着时间推移病理事件的级联反应。本研究的目的是使用一系列感觉运动功能测试来检查大鼠脑出血后的神经学效应，并检查血肿的哪些成分参与产生这些效应。
所使用的行为测试包括前肢放置、在圆柱形围栏垂直探索过程中体重转移时前肢使用偏好以及转角测试。在注射自体全血、注射血液加水蛭素（凝血酶抑制剂）、浓缩红细胞、凝血酶或生理盐水后，或仅进行针头放置后，从第1天到第28天对大鼠进行测试。
一系列测试表明，脑出血后第1天即出现明显的神经功能缺损，功能在4周内逐渐恢复。前肢放置评分与水肿变化平行。注射凝血酶会导致脑出血诱导的神经功能缺损，而注射水蛭素可减轻这种缺损。注射浓缩红细胞会导致延迟性水肿形成，并诱发延迟性神经功能缺损。
这些测试可对大鼠脑出血后的神经功能缺损进行持续监测，并评估治疗干预措施。神经功能缺损的时间进程与脑出血及血液成分注射后脑水肿的时间进程密切匹配。脑出血后功能有明显恢复，这可能适合进行治疗性干预。
