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

皮层神经元易受缺氧的影响，这在梗死区域内神经元的神经病理改变中是已知的。在本研究中，我们检测了大脑中动脉（MCA）永久性单侧闭塞引起局灶性脑缺血后皮层神经元的早期组织病理变化。在实验动物中，局灶内皮层神经元在MCA区域内迅速发生细胞死亡，而缺血半暗带内的神经元在缺血损伤后表现出相对延迟的神经元死亡。然而，这些神经元的死亡是坏死还是凋亡尚不明确。我们观察了局灶性缺血后大脑皮层皮层神经元和缺血半暗带的退化过程。缺血损伤后2小时，病灶区域内的神经元特征已经改变为相对扩大的形状。这些神经元的质膜破碎，细胞器碎片散落在细胞质中。细胞核膨大，分裂成碎块，细胞壁碎块散落在细胞质中。扩大的神经元核表达TUNEL阳性反应。另一方面，缺血半暗区在缺血后6 s内可见典型的坏死肿胀神经元和高电子密度的小神经元。后一种神经元表现出细胞萎缩，并伴有对囊状半胱氨酸蛋白酶的免疫反应性增加。损伤后1 ~ 3 d，这些神经元的细胞核呈现TUNEL阳性反应。退化的神经元被侵入的吞噬细胞异噬。这些结果表明，MCA闭塞局灶性缺血后，局灶区皮层神经元的成年死亡是坏死的，而缺血半暗区神经元的死亡则是坏死和凋亡。

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.