Magloczky Z, Freund T F
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Neuroscience. 1993 Sep;56(2):317-35. doi: 10.1016/0306-4522(93)90334-c.
Intracerebral or intraperitoneal injections of kainic acid, an agonist at a class of glutamate receptors, have been extensively used to model temporal lobe epilepsy. In the present study we compared the types and distributions of selectively vulnerable neurons in the ipsi- and contralateral hippocampi following unilateral kainate injections into the CA3 subfield in order to examine whether "proximal" or "distant" neuronal damage resembled the pathology, and possibly also the mechanism, of human temporal lobe epilepsy. The degeneration of principal cells in the different hippocampal subfields was visualized by silver impregnation, and the loss of various types of non-principal cells was studied by immunostaining for the calcium binding proteins parvalbumin, calbindin-D28k and calretinin, as well as for somatostatin. In the first series of experiments various concentrations (ranging from 0.1 to 1 mg/ml) and volumes (0.5-2 microliters) of kainate were tested to induce reproducible damage in the contralateral hippocampus. The optimal dose, employed in the subsequent vulnerability studies, was found to be 3 x 0.5-microliter injections (over a period of 10 min) of a concentration of 0.33 mg/ml under ether anaesthesia, which was discontinued immediately after injection. Anaesthesia with equithesin was found to prevent contralateral cell death. Most if not all pyramidal cells in the CA3 region degenerated on the ipsilateral side, whereas the dentate granule cells, and the majority of CA1 pyramidal cells were resistant. A strikingly different pattern was found on the contralateral side, where CA1 pyramidal cells were almost completely lost, but the CA3 region (with the exception of CA3c) and the dentate gyrus remained intact. Three subpopulations of non-principal cells were found to be vulnerable in both hemispheres, the hilar somatostatin cells, spiny calretinin cells and mossy cells, as well as the spiny calretinin cells in stratum lucidum of CA3. The other subpopulations were resistant, except for those within the effective injection site. We propose that the "distant" (contralateral) damage resembles the pattern, and probably also the mechanism, of cell death in human temporal lobe epilepsy, whereas the ipsilateral damage does not.
将一类谷氨酸受体的激动剂海藻酸进行脑内或腹腔注射，已被广泛用于模拟颞叶癫痫。在本研究中，我们比较了在将海藻酸单侧注射到CA3亚区后，同侧和对侧海马中选择性易损神经元的类型和分布，以检验“近端”或“远端”神经元损伤是否类似于人类颞叶癫痫的病理情况，甚至可能还类似于其发病机制。通过银浸染观察不同海马亚区中主要细胞的变性情况，并通过对钙结合蛋白小白蛋白、钙结合蛋白-D28k、钙视网膜蛋白以及生长抑素进行免疫染色，研究各类非主要细胞的损失情况。在第一系列实验中，测试了不同浓度（范围为0.1至1毫克/毫升）和体积（0.5 - 2微升）的海藻酸，以在对侧海马中诱导可重复的损伤。在随后的易损性研究中所采用的最佳剂量，是在乙醚麻醉下以0.33毫克/毫升的浓度进行3次0.5微升注射（在10分钟内完成），注射后立即停止麻醉。发现使用氨基巴比妥麻醉可防止对侧细胞死亡。同侧CA3区的大多数（如果不是全部的话）锥体细胞发生变性，而齿状颗粒细胞以及大多数CA1锥体细胞具有抗性。在对侧发现了一种截然不同的模式，其中CA1锥体细胞几乎完全丧失，但CA3区（CA3c除外）和齿状回保持完整。发现有三个非主要细胞亚群在两个半球中都易受损，即门区生长抑素细胞、棘状钙视网膜蛋白细胞和苔藓细胞，以及CA3透明层中的棘状钙视网膜蛋白细胞。其他亚群具有抗性，但有效注射部位内的细胞除外。我们提出，“远端”（对侧）损伤类似于人类颞叶癫痫中的细胞死亡模式，甚至可能还类似于其机制，而同侧损伤则不然。
