Winkler D T, Scotti A L, Nitsch C
Institute of Anatomy, University of Basel, Switzerland.
Exp Neurol. 2001 Apr;168(2):364-72. doi: 10.1006/exnr.2000.7605.
Mongolian gerbils are epilepsy-prone animals. In adult gerbils two major groups can be differentiated according to their seizure behavior: Highly seizure-sensitive gerbils exhibit facial and forelimb clonus or generalized tonic-clonic seizures from the first test on, while kindled-like gerbils are seizure free for the first three to six consecutive tests, later develop forelimb myoclonus, and eventually progress to generalized tonic-clonic seizures. In the hippocampus, seizure history of the individual animal is mirrored in the intensity in which GABAergic neurons are immunostained for the calcium-binding protein parvalbumin: they lose parvalbumin with increasing seizure incidence. In a first step to clarify the influence of hippocampal projection neurons on spontaneous seizure behavior and related parvalbumin expression, we induced degeneration of the CA1 pyramidal cells by transient forebrain ischemia. This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils. The kindling-like process, however, is not permanently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. The seizure-induced loss of parvalbumin from the ischemia-resistant interneurons recovers after ischemia. Thus, changes in parvalbumin content brought about by repeated seizures are not permanent but can rather be modulated by novel stimuli.
蒙古沙鼠是易患癫痫的动物。在成年沙鼠中，根据其癫痫发作行为可分为两大组：高度癫痫敏感的沙鼠从首次测试开始就表现出面部和前肢阵挛或全身性强直阵挛发作，而点燃样沙鼠在连续的前三次至六次测试中无癫痫发作，随后发展为前肢肌阵挛，最终进展为全身性强直阵挛发作。在海马体中，个体动物的癫痫发作史反映在γ-氨基丁酸能神经元对钙结合蛋白小白蛋白免疫染色的强度上：随着癫痫发作发生率的增加，它们会失去小白蛋白。为了阐明海马投射神经元对自发性癫痫发作行为和相关小白蛋白表达的影响，我们通过短暂性前脑缺血诱导CA1锥体细胞变性。这导致高度癫痫敏感的沙鼠癫痫敏感性降低。然而，点燃样过程并未因缺血性神经细胞损失而永久阻断，这表明完整的CA1区域不是癫痫发作行为发展的先决条件。癫痫发作导致的抗缺血中间神经元中小白蛋白的丢失在缺血后恢复。因此，反复癫痫发作引起的小白蛋白含量变化不是永久性的，而是可以由新的刺激调节的。
