Fukuda T, Nakano S, Yoshiya I, Hashimoto P H
Department of Anesthesiology, Osaka University Medical School, Japan.
Neuroscience. 1993 Mar;53(1):23-38. doi: 10.1016/0306-4522(93)90281-j.
Morphological changes in the neurons of the gerbil hippocampus following 5 min of forebrain ischemia were examined using light and electron microscopy. Although non-pyramidal neurons in the CA1 region of the hippocampus survived through the full length of the observation period, up to six weeks after ischemia, they consistently demonstrated degenerative changes distinct from those of the well-known "delayed neuronal death" of CA1 pyramidal cells. When examined with the light microscope, CA1 non-pyramidal neurons were found to be shrunken and their nuclei and cytoplasm were hyperchromatic between seven days and six weeks after ischemia. When examined with the electron microscope, postischemic non-pyramidal neurons were found to have markedly electron-dense profiles; their cytoplasm contained numerous free ribosomes and heterogeneous smaller granular substances, the latter also filling the nuclei. However, there was no loss of ribosomes from the rough endoplasmic reticulum, and mitochondrial cristae were preserved, suggesting that these neurons were viable. CA1 non-pyramidal neurons were studied immunohistochemically using three types of monoclonal antibodies, one each against parvalbumin, a nonphosphorylated epitope on the 168,000 mol. wt and 200,000 mol. wt subunits of neurofilament proteins, and microtubule-associated protein 2. CA1 non-pyramidal neurons lost immunoreactivity to these neuron-specific substances six weeks after ischemia, suggesting that these degenerating cells lacked certain types of normal neuronal activity. We conclude that non-pyramidal neurons in the hippocampal CA1 region survive transient ischemia but undergo degenerative changes following complete loss of CA1 pyramidal cells. These changes may be due to depletion of presumptive target-derived trophic factors within the non-pyramidal neurons.
采用光学显微镜和电子显微镜检查沙土鼠前脑缺血5分钟后海马神经元的形态学变化。尽管海马CA1区的非锥体神经元在整个观察期内存活下来，直至缺血后六周，但它们始终表现出与CA1锥体细胞众所周知的“延迟性神经元死亡”不同的退行性变化。在光学显微镜下检查时，发现缺血后7天至6周期间，CA1区非锥体神经元萎缩，其细胞核和细胞质染色质增多。在电子显微镜下检查时，发现缺血后的非锥体神经元具有明显的电子致密轮廓；其细胞质含有大量游离核糖体和大小不一的较小颗粒物质，后者也充满细胞核。然而，粗面内质网的核糖体没有丢失，线粒体嵴得以保留，这表明这些神经元是有活力的。使用三种单克隆抗体对CA1区非锥体神经元进行免疫组织化学研究，这三种抗体分别针对小白蛋白、分子量为168,000道尔顿和200,000道尔顿的神经丝蛋白亚基上的非磷酸化表位以及微管相关蛋白2。缺血六周后，CA1区非锥体神经元对这些神经元特异性物质失去免疫反应性，这表明这些退化细胞缺乏某些类型的正常神经元活动。我们得出结论，海马CA1区的非锥体神经元在短暂缺血后存活，但在CA1锥体细胞完全丧失后会发生退行性变化。这些变化可能是由于非锥体神经元内假定的靶源性营养因子耗竭所致。
