MECHANISNS OF NEURONAL DEQTH IN THE RAT (SHRSP) CEREBRAL CORTEX FOLLOEING FOCAL PERMANENT ISCHEMIA BY MIDDLE CEREBRAL ARTERY OCCLUSION

众所周知，大脑皮质神经元容易受到缺氧的影响，这会导致梗死区内神经元的神经病理变化。在本研究中，我们观察了大脑中动脉永久性单侧闭塞(MCA)所致的局灶性脑缺血后皮质神经元的早期组织病理学变化。实验动物大脑中动脉局灶区梗死区内皮质神经元迅速死亡，而缺血半暗带内神经元在缺血损伤后死亡相对较迟。然而，目前尚不清楚这些神经元的死亡是坏死还是凋亡。我们观察了局灶性脑缺血后大脑皮层局灶区和缺血半暗带内皮质神经元的变性过程。在缺血后2小时，病灶区域内的神经元已经改变了它们的特征，变成了相对扩大的形状。这些神经元的质膜破碎成碎片，解体的细胞器碎片散落在细胞质中。这些细胞的扩张核破碎成碎片，胞质内散布着解体的小孔碎片。这些神经元的扩张核呈TUNEL阳性反应。而缺血后6FRS的缺血半暗带内可见典型的坏死性肿胀神经元和高电子密度的小神经元。后一种神经元出现细胞萎缩，同时半胱氨酸蛋白酶免疫反应增强。损伤后1~3d，这些神经元的胞核均呈TUNEL阳性反应。变性神经元被侵入该区域的吞噬细胞异噬。这些结果表明，大脑中动脉闭塞局灶性脑缺血后局灶区皮质神经元成年期死亡为坏死性死亡，而缺血半暗区神经元死亡主要由坏死性炎症和细胞凋亡组成。

The cortical neurons are known to be vulnerable to anoxic, which in neuropathological changes of the neurons within the infarcted area. In the present study, we examined early histo-pathological changes in the cortical neurons after focal cerebrai, ischemia, induced by permanent unilateral occlusion of the middle cerebral artery (MCA). In the experimental animals infarcted cortical neurons within the focal wrea at the territory of MCA rapidly underwent cell death, while the neurins within ischemic penumbra exhibited relatively delayd neuronal death after ischemic insult. It remain, however, undefined whether death of these neurons are necrosis or apoptosis. We examined the degenerating process of the cortical neurons within the focal area and ischemic penumbra of cerebral cortex after focal ischemia. At 2 hrs after ischemic insults neurons within the focal area already changed their feature into relatively expanded shapes. Plasma membrane of these neurons was broken into pieces and fragments of disintegrated organelles scattered whithin cytoplasm. Expanded Nuclei of these broken into pieces and fragments of disintegrated oranelles scattered within cytoplasm. Expanded Nuclei of these neurons expressed TUNEL positive reaction. On the other hand, typical necrotic swelling neurons and highiy electron dense small ones were detected within the ischemic penumbra at 6 frs after ischemia. The latter neurons exhibited cell shrinkage accompanied with an increase in immunoreactivity for iysosmal cystein proteinases. Nuclei of these neurons showed TUNEL positive reacition from 1 to 3 days after insults. Degenerated neurons were heterophagocytosed by phagocytes invaded into the area. These results suggest that aduth death of the cortical neurons within the focal area after focal ischemia by MCA occlusion is necrotic, whereas neuronal death the ischemic penumbra consisted of necrotis and apoptoti.