Nadler J V, Perry B W, Gentry C, Cotman C W
J Comp Neurol. 1980 Jul 15;192(2):333-59. doi: 10.1002/cne.901920209.
Degeneration of hippocampal CA3 pyramidal cells was investigated by light and electron microscopy after intraventricular injection of the potent convulsant, kainic acid. Electron microscopy revealed evidence of pyramidal cell degeneration within one hour. The earliest degenerative changes were confined to the cell body and proximal dendritic shafts. These included an increased incidence of lysosomal structures, deformation of the perikaryal and nuclear outlines, some increase in background electron density, and dilation of the cisternae of the endoplasmic reticulum accompanied by detachment of polyribosomes. Within the next few hours the pyramidal cells atrophied and became electron dense. Then these cells became electron lucent once more as ribosomes disappeared and their membranes and organelles broke up and disintegrated. Light microscopic changes correlated with these ultrastructural observations. The dendritic spines and the initial portion of the dendritic shaft became electron dense within four hours and degenerated rapidly, whereas the intermediate segment of the dendrites swelled moderately and became more electron lucent. No degenerative changes were evident in pyramidal cell axons and boutons until one day after kainic acid treatment. Less than one hour after kainic acid administration, astrocytes in the CA3 area swelled, initially in the vicinity of the cell body and mossy fiber layers. It is suggested that the paroxysmal discharges initiated in CA3 pyramidal cells by kainic acid served as the stimulus for this response. Phagocytosis commenced between one and three days after kainic acid administration, but remained incomplete at survival times of 6-8 weeks. Astrocytes, microglia, and probably oligodendroglia phagocytized the degenerating material. These results point to the pyramidal cell body and possibly also the dendritic spines as primary targets of kainic acid neurotoxicity. In conjunction with other data, they support the view that lesions made by intraventricular kainic acid can serve as models of epileptic brain damage.
通过脑室注射强效惊厥剂 kainic 酸后，利用光学显微镜和电子显微镜研究海马 CA3 锥体细胞的变性。电子显微镜显示在一小时内就有锥体细胞变性的证据。最早的退行性变化局限于细胞体和近端树突轴。这些变化包括溶酶体结构发生率增加、核周和核轮廓变形、背景电子密度略有增加以及内质网池扩张并伴有多核糖体脱离。在接下来的几个小时内，锥体细胞萎缩并变得电子致密。然后，随着核糖体消失且其膜和细胞器破裂解体，这些细胞再次变得电子透亮。光学显微镜下的变化与这些超微结构观察结果相关。树突棘和树突轴的起始部分在四小时内变得电子致密并迅速退化，而树突的中间段适度肿胀并变得更电子透亮。直到 kainic 酸处理一天后，锥体细胞轴突和终扣才出现明显的退行性变化。在给予 kainic 酸后不到一小时，CA3 区域的星形胶质细胞肿胀，最初在细胞体和苔藓纤维层附近。有人认为 kainic 酸在 CA3 锥体细胞中引发的阵发性放电是这种反应的刺激因素。吞噬作用在给予 kainic 酸后 1 至 3 天开始，但在存活 6 - 8 周时仍未完成。星形胶质细胞、小胶质细胞以及可能还有少突胶质细胞吞噬了退化物质。这些结果表明锥体细胞体以及可能还有树突棘是 kainic 酸神经毒性的主要靶点。结合其他数据，它们支持脑室注射 kainic 酸造成的损伤可作为癫痫性脑损伤模型的观点。
