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 gr oups can be differentiated according to their seizure behavior: Highly seiz ure-sensitive gerbils exhibit facial and forelimb clonus or generalized ton ic-clonic seizures from the first test on, while kindled-like gerbils are s eizure free for the first three to six consecutive tests, later develop for elimb myoclonus, and eventually progress to generalized tonic-clonic seizur es. In the hippocampus, seizure history of the individual animal is mirrore d in the intensity in which GABAergic neurons are immunostained for the cal cium-binding protein parvalbumin: they lose parvalbumin with increasing sei zure incidence. In a first step to clarify the influence of hippocampal pro jection neurons on spontaneous seizure behavior and related parvalbumin exp ression, we induced degeneration of the CA1 pyramidal cells by transient fo rebrain ischemia, This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils, The kindling-like process, however, is not perm anently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. Th e seizure-induced loss of parvalbumin from the ischemia-resistant interneur ons recovers after ischemia, Thus, changes in parvalbumin content brought a bout by repeated seizures are not permanent but can rather be modulated by novel stimuli. (C) 2001 Academic Press.