Lowenstein D H, Simon R P, Sharp F R
Department of Neurology, University of California, San Francisco 94110.
Brain Res. 1990 Oct 29;531(1-2):173-82. doi: 10.1016/0006-8993(90)90771-3.
The inducible 72-kDa heat shock protein (HSP72) is a highly conserved stress protein that is expressed in CNS cells and may play a role in protection from neural injury. We used a monoclonal antibody to HSP72 and immunocytochemistry to localize HSP72 in the rat brain 24 h following either 30 or 60 min of flurothyl-induced status epilepticus. Sprague-Dawley rats were anesthetized with halothane, paralyzed, and ventilated, and remained normotensive and well oxygenated for the duration of the seizures. Seizure activity was quantified via analysis of the scalp EEG pattern. HSP72-like immunoreactivity (HSP72-LI) was induced in specific brain regions in a graded fashion that correlated, in part, with the duration and degree of seizure activity. Milder seizures produced HSP72-LI limited to layers 2 and 3 of frontoparietal cortex, dentate hilus cells, and CA3 pyramidal neurons. More extensive seizures led to HSP72-LI in layers 2, 3 and 5 of frontoparietal and visual cortex, dentate hilus cells, CA1 and CA3 pyramidal neurons, and certain thalamic and amygdaloid nuclei. These are similar to many, but not all, of the brain regions known to be injured with this model. No HSP72-LI was observed in sham-treated controls or flurothyl-treated animals whose seizures were controlled with pentobarbital. HSP72-LI thus localizes to certain regions of seizure-induced injury, and may provide a sensitive method of detecting neuronal 'stress' or injury relatively soon after status epilepticus. Whether or not HSP72 synthesis plays a protective role in the pathogenesis of seizures, or is only a marker for cell injury, remains to be determined.
诱导型72-kDa热休克蛋白（HSP72）是一种高度保守的应激蛋白，在中枢神经系统细胞中表达，可能在保护神经元免受损伤方面发挥作用。我们使用抗HSP72单克隆抗体和免疫细胞化学方法，在氟烷诱导癫痫持续状态30或60分钟后24小时，定位大鼠脑中的HSP72。将Sprague-Dawley大鼠用氟烷麻醉、麻痹并进行通气，在癫痫发作期间保持血压正常和氧合良好。通过分析头皮脑电图模式对癫痫活动进行量化。HSP72样免疫反应性（HSP72-LI）在特定脑区以分级方式诱导产生，部分与癫痫活动的持续时间和程度相关。较轻的癫痫发作使HSP72-LI局限于额顶叶皮层第2和第3层、齿状回门区细胞以及CA3锥体神经元。更广泛的癫痫发作导致额顶叶和视觉皮层第2、3和5层、齿状回门区细胞、CA1和CA3锥体神经元以及某些丘脑和杏仁核出现HSP72-LI。这些区域与已知受该模型损伤的许多但并非所有脑区相似。在假手术对照组或用戊巴比妥控制癫痫发作的氟烷处理动物中未观察到HSP72-LI。因此，HSP72-LI定位于癫痫诱导损伤的某些区域，并且可能提供一种在癫痫持续状态后相对较快地检测神经元“应激”或损伤的灵敏方法。HSP72合成在癫痫发病机制中是否发挥保护作用，或者仅仅是细胞损伤的标志物，仍有待确定。
