Department of Biomedical Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Neuroscience. 2012 Aug 30;218:278-94. doi: 10.1016/j.neuroscience.2012.05.018. Epub 2012 May 17.
Status epilepticus (SE) induced by pilocarpine or kainate is associated with yet not systemically investigated astrocytic and vascular injuries. To investigate their possible association with neuronal damage, the changes in glial fibrillary acidic protein (GFAP), laminin and neuron-specific nuclear protein (NeuN) immunoreactivities were analyzed in rats treated with pilocarpine (380 mg/kg) or kainate (15 mg/kg), and receiving diazepam (20mg/kg) after 10 min of SE. A different group of rats was injected with endothelin-1 (ET-1) in the caudate putamen to reproduce the changes in GFAP and laminin immunoreactivities associated with ischemia. Focal loss of GFAP immunostaining was accompanied by increased laminin immunoreactivity in blood vessels, in all the examined groups. Regression analysis revealed a significant (P<0.01) relationship between astrocytic lesion and increased laminin immunoreactivity in the piriform cortex (Pir) of both pilocarpine (R(2)=0.88) and kainate (R(2)=0.94) groups of treatment. A significant relationship (P<0.01; R(2)=0.81) was also present in the cornu Ammonis 3 (CA3) hippocampal region of pilocarpine-treated rats. At variance, neuronal and glial lesions were significantly related (P<0.05, R(2)=0.74) only in the substantia nigra of pilocarpine-treated rats. The ratio between areas of GFAP and laminin changes of immunoreactivity in the ET-1 group was similar to those found in pilocarpine- and kainate-treated rats in specific brain regions, such as the hippocampal CA3 subfield, Pir and the anterior olfactory nucleus. The amygdala and submedius thalamic nucleus in the pilocarpine group, and the perirhinal and entorhinal cortices in the kainate group, also presented ischemic-like changes. These results indicate that laminin immunoreactivity is upregulated in the basal lamina of blood vessels after SE induced by pilocarpine or kainate. This phenomenon is significantly associated with lesions involving more glial than neuronal cells, in specific cerebral regions.
癫痫持续状态（SE）由匹罗卡品或海人酸诱导，与星形胶质细胞和血管损伤有关，但尚未进行系统研究。为了研究它们与神经元损伤的可能联系，我们分析了用匹罗卡品（380mg/kg）或海人酸（15mg/kg）处理大鼠后，给予地西泮（20mg/kg）10min 后，神经胶质纤维酸性蛋白（GFAP）、层粘连蛋白和神经元特异性核蛋白（NeuN）免疫反应的变化。另一组大鼠在尾状核内注射内皮素-1（ET-1），以复制与缺血相关的 GFAP 和层粘连蛋白免疫反应变化。在所有检查的组中，GFAP 免疫染色的局灶性丧失伴随着血管中层粘连蛋白免疫反应的增加。回归分析显示，星形胶质细胞病变与匹罗卡品（Pir）和海人酸（R（2）=0.94）两组治疗的梨状皮质（Pir）中增加的层粘连蛋白免疫反应之间存在显著（P<0.01）关系。在匹罗卡品治疗的大鼠的 CA3 海马区也存在显著关系（P<0.01；R（2）=0.81）。然而，神经元和神经胶质病变仅在匹罗卡品治疗的大鼠的黑质中与 GFAP 和层粘连蛋白免疫反应的变化密切相关（P<0.05，R（2）=0.74）。在 ET-1 组中，GFAP 和层粘连蛋白免疫反应变化的面积比在匹罗卡品和海人酸治疗的大鼠的特定脑区（如海马 CA3 亚区、Pir 和前嗅核）中发现的更为相似。匹罗卡品组的杏仁核和丘脑下核，以及海人酸组的梨状皮层和内嗅皮层也呈现出类似缺血的变化。这些结果表明，匹罗卡品或海人酸诱导的 SE 后，血管基底膜中的层粘连蛋白免疫反应增加。这种现象与特定脑区中涉及更多胶质细胞而非神经元细胞的病变显著相关。
