Vass K, Welch W J, Nowak T S
Laboratory of Neuropathology and Neuroanatomical Sciences, NINCDS, Bethesda, MD 20892.
Acta Neuropathol. 1988;77(2):128-35. doi: 10.1007/BF00687422.
Induction of the 70-kDa heat shock protein, hsp70, has been demonstrated in brain following experimental stroke. In the present study, hsp70 was localized in gerbil brain at intervals after transient ischemia using a monoclonal antibody specific for stress-inducible forms of hsp70-related proteins. Induced immunoreactivity was found only in neurons, primarily in hippocampus, striatum, entorhinal cortex and some neocortical regions. Notably hsp70 accumulation was minimal in hippocampal CA1 neurons which die after brief ischemic episodes, but was most pronounced in dentate granule cells and CA3 neurons which are spared. The peak of CA3 immunoreactivity occurred at 48-h recirculation, at the onset of CA1 neuron loss at 2-4 days, demonstrating that hsp70 induction is also a component of this delayed hippocampal pathophysiology rather than a direct response to the metabolic disruption of the initial ischemic episode. These results suggest that hsp70 immunocytochemistry may serve as a marker for neuronal circuitry involved in proposed excitotoxic mechanisms after ischemia and other stresses. Control animals showed immunoreactivity in ependymal cells lining the ventricles, indicating a role for hsp70 in normal functioning of these specialized cells.
实验性中风后，已证实在大脑中可诱导产生70 kDa热休克蛋白（hsp70）。在本研究中，使用针对hsp70相关蛋白应激诱导形式的单克隆抗体，在短暂性脑缺血后的不同时间间隔，对沙鼠脑内的hsp70进行定位。诱导的免疫反应仅在神经元中发现，主要位于海马体、纹状体、内嗅皮质和一些新皮质区域。值得注意的是，在短暂缺血发作后死亡的海马CA1神经元中，hsp70的积累极少，但在未受损的齿状颗粒细胞和CA3神经元中最为明显。CA3免疫反应的峰值出现在再灌注48小时时，即CA1神经元在2 - 4天开始死亡时，这表明hsp70的诱导也是这种延迟性海马病理生理学的一个组成部分，而不是对初始缺血发作代谢紊乱的直接反应。这些结果表明，hsp70免疫细胞化学可能作为一种标记，用于指示缺血和其他应激后所提出的兴奋性毒性机制中涉及的神经回路。对照动物在脑室衬里的室管膜细胞中显示出免疫反应，表明hsp70在这些特殊细胞的正常功能中发挥作用。
