Ischemia-induced degeneration of CA1 pyramidal cells decreases seizure severity in a subgroup of epileptic gerbils and affects parvalbumin immunoreactivity of CA1 interneurons.
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.
Institute of Anatomy, University of Basel, Switzerland.
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DT
Winkler
A L
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Scotti
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C
Nitsch
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D004827:Epilepsy / Q000378:metabolism* / Q000517:prevention & control; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats
D010320:Parvalbumins