Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation
Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation
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DOI：
10.3171/jns.1996.85.1.0138
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发表时间：
1996-07-01
影响因子：
4.1
通讯作者：
Weinstein, PR
中科院分区：
文献类型：
--
作者：
Matz, PG;Sundaresan, S;Weinstein, PR
目前对蛛网膜下腔出血（SAH）的实验研究受到限制，因为缺乏生理上类似于SAH的小动物模型，并且始终显示急性和延迟性细胞损伤。近年来，我们建立了大鼠颈动脉血管内穿孔诱导SAH的模型。该模型在生理上类似于SAH。然而，在这种或其他模型中，详细描述SAH后细胞损伤的组织学数据很少。使用免疫细胞化学，作者研究了70-kD热休克蛋白（HSP70）的诱导，HSP70是血管内SAH后1天和5天大脑中细胞应激或损伤的敏感标志物。作者还使用甲酚紫和苏木精和伊红染色的常规组织学技术来研究血管内SAH后1和5天的细胞损伤。SAH后1天，在所有6只动物的多个解剖区域（包括基底前脑、丘脑、新皮层、纹状体和海马）诱导HSP70。这种HSP70诱导在双侧多个血管分布中观察到。HSP70的免疫染色主要发生在神经元中，但也见于胶质细胞和内皮细胞。SAH后5天，在所有8只动物中观察到类似但更强烈的HSP70免疫染色模式。具体来说，在第5天（8只动物中有6只），海马至少一个区域的HSP70免疫反应性比第1天更频繁（6只动物中有1只，p < 0.05，单尾Fisher精确检验）。对照组动物在第1天和第5天均未见HSP70免疫染色。常规组织学显示缺血性神经元损伤灶和细胞坏死；然而，在1天和5天的所有动物中，HSP70免疫细胞化学对细胞损伤的详细描述远远优于常规组织学。我们的研究结果表明，在血管内SAH发生1天和5天后，HSP70在多个区域和细胞类型中被诱导。由于缺血是一种已知的应激基因诱导剂，作者提出急性和延迟缺血是诱导HSP70的过程，分别在第1天和第5天观察到。研究血管内SAH后HSP70诱导也可以作为一种新的、廉价的动物模型的基础，以评估潜在的治疗干预措施。
Current experimental research on subarachnoid hemorrhage (SAH) has been limited by the lack of a small-animal model that physiologically resembles SAH and consistently demonstrates acute and delayed cellular injury. Recently, a model for inducing SAH by endovascular perforation of the internal carotid artery has been developed in the rat. This model physiologically resembles SAH. However, little histological data detailing cellular injury after SAH are available in this or other models. Using immunocytochemistry, the authors investigated the induction of the 70-kD heat shock protein, HSP70, a sensitive marker for cellular stress or injury in the brain, 1 and 5 days following endovascular SAH. The authors also used the conventional histological techniques of cresyl violet and hematoxylin and eosin staining to investigate cellular damage 1 and 5 days after the endovascular SAH.One day following the SAH, HSP70 was induced in all six animals examined in multiple anatomical regions, including the basal forebrain, thalamus, neocortex, striatum, and hippocampus. This HSP70 induction was observed in multiple vascular distributions bilaterally. Immunostaining with HSP70 occurred primarily in neurons but also was observed in glia and endothelium. Five days after the SAH, a similar but more intense pattern of HSP70 immunostaining was observed in all eight animals examined. Specifically, HSP70 immunoreactivity was observed in at least one region of the hippocampus more often at 5 days (six of eight animals) than at 1 day (one of six animals, p < 0.05, one-tailed Fisher's exact test). No HSP70 immunostaining was observed in control animals at 1 day or at 5 days. Conventional histology demonstrated foci of ischemic neuronal damage and cellular necrosis; however, HSP70 immunocytochemistry detailed cellular injury far better than conventional histology in all animals tested at both 1 day and 5 days.Our results demonstrate that HSP70 is induced in multiple regions and cell types 1 day and 5 days following endovascular SAH. Because ischemia is a known inducer of stress genes, the authors propose that acute and delayed ischemia are the processes responsible for the induction of HSP70 that was observed at 1 day and 5 days, respectively. Investigation of HSP70 induction following endovascular SAH may also serve as the basis for a new, inexpensive animal model to assess potential therapeutic interventions.