EFFECTS OF IMIPENEM ON NEUROGENESIS, ASTROGLIAL RESPONSE AND COGNITIVE FUNCTION IN A PTZ-KINDLED RAT MODEL OF EPILEPSY

The present study investigated the effects of imipenem on hippocampal neurogenesis, astroglial responses, and behavioral performance in an experimental model of epileptogenesis. Five-month-old Wistar rats were allocated into three experimental groups: PTZ, Imipenem, and PTZ plus Imipenem. Epileptogenesis was induced in the PTZ and PTZ plus Imipenem groups by administering subconvulsive doses of pentylenetetrazole on alternate days until animals reached a kindled state or displayed epileptic manifestations. After kindling, rats in the Imipenem and PTZ plus Imipenem groups received daily intraperitoneal injections of imipenem at a dose of forty milligrams per kilogram for ten consecutive days. Behavioral and cognitive functions were subsequently evaluated using the Morris water maze, open-field test, and elevated plus maze. Following behavioral assessments, animals were euthanized and brain tissue was collected for immunohistochemical analysis of doublecortin and glial fibrillary acidic protein expression.

Pentylenetetrazole-induced kindling resulted in pronounced impairments in spatial learning and working memory. These deficits were further exacerbated by imipenem co-administration, as animals in the PTZ plus Imipenem group failed to reach control-level performance during the final training sessions of the Morris water maze. Probe trial analysis revealed reduced spatial memory retention in both PTZ-treated groups, indicating disrupted long-term memory processing. Although anxiety-like behavior was increased in the elevated plus maze following PTZ exposure, locomotor activity in the open-field test remained unchanged. Immunohistochemical analyses mirrored the behavioral findings, showing that PTZ alone induced increased doublecortin expression and astrocytic hypertrophy, whereas imipenem treatment attenuated neurogenic responses and altered astroglial morphology.