Matz P G, Weinstein P R, Sharp F R
Department of Neurology, University of California at San Francisco, USA.
Neurosurgery. 1997 Jan;40(1):152-60; discussion 160-2. doi: 10.1097/00006123-199701000-00034.
Current experimental evidence demonstrates the development of ischemic regions adjacent to and spatially remote from an intracerebral hematoma. The cause of this ischemia is uncertain. Because ischemia is a known inducer of stress genes, we investigated the induction of two stress proteins, heme oxygenase (HO)-1 and heat shock protein (Hsp) 70, after intracerebral hemorrhage in the rat.
Immunocytochemistry for HO-1, Hsp70, and HO-2, the constitutive isoform of the HO enzyme, was performed 1, 2, and 4 days after striatal injection of saline, whole blood, or lysed blood. Immunocytochemistry for HO-1, HO-2, and Hsp70 was also performed 1 day after cortical injection of saline, whole blood, or lysed blood.
After striatal injection of lysed and whole blood, the HO-1 protein was induced in glia throughout the hemisphere ipsilateral to the hematoma, and HO-1 immunoreactivity persisted for at least 4 days. After cortical injection of lysed and whole blood, HO-1 was induced in glia throughout the neocortex. Neuronal induction of HO-1 was also observed after cortical injection of lysed blood but not whole blood or saline. After striatal injection of lysed blood, Hsp70 was induced in glia surrounding the hematoma and in neurons from the neocortex overlying the hematoma and the striatum adjacent to the hematoma. After cortical injection of lysed blood, Hsp70 was induced in neurons throughout the neocortex and hippocampus bilaterally. In contrast, after whole blood and saline injection into cortex, Hsp70 induction was observed only in scattered neurons surrounding the hematoma cavity.
Our results demonstrate that blood in the brain parenchyma induces the HO-1 stress protein but does not significantly alter HO-2 immunostaining. Our results also demonstrate that lysed blood induces Hsp70 in multiple regions of the brain and that the stress response of the brain differs depending on whether lysed blood is injected into the cortex or striatum. These results suggest that blood lysis may play an unforeseen role in the stress response of the brain to intracerebral hemorrhage.
目前的实验证据表明，在脑内血肿周围及空间上远离血肿的区域会出现缺血区域。这种缺血的原因尚不确定。由于缺血是应激基因的已知诱导因素，我们研究了大鼠脑出血后两种应激蛋白，即血红素加氧酶（HO）-1和热休克蛋白（Hsp）70的诱导情况。
在纹状体注射生理盐水、全血或溶血后1天、2天和4天，对HO-1、Hsp70以及HO酶的组成型同工型HO-2进行免疫细胞化学检测。在皮质注射生理盐水、全血或溶血后1天，也对HO-1、HO-2和Hsp70进行免疫细胞化学检测。
纹状体注射溶血和全血后，血肿同侧半球的胶质细胞中诱导出HO-1蛋白，且HO-1免疫反应性持续至少4天。皮质注射溶血和全血后，整个新皮质的胶质细胞中诱导出HO-1。皮质注射溶血后也观察到神经元中HO-1的诱导，但全血或生理盐水注射后未观察到。纹状体注射溶血后，血肿周围的胶质细胞以及血肿上方新皮质和血肿相邻纹状体的神经元中诱导出Hsp70。皮质注射溶血后，双侧整个新皮质和海马体的神经元中诱导出Hsp70。相比之下，向皮质注射全血和生理盐水后，仅在血肿腔周围的散在神经元中观察到Hsp70的诱导。
我们的结果表明，脑实质内的血液可诱导HO-1应激蛋白，但不会显著改变HO-2免疫染色。我们的结果还表明，溶血可在脑的多个区域诱导Hsp70，且脑的应激反应因溶血是注射到皮质还是纹状体而有所不同。这些结果表明，血液溶解可能在脑对脑出血的应激反应中发挥意想不到的作用。
