Impact of Imipenem on Cognitive Function, Anxiety-like Behaviour, Neurogenesis, and Astrogliosis in...

Background/Objectives: Adverse neurological events caused by imipenem are usually more frequent in patients with epilepsy. This study investigates the effects of imipenem on hippocampal neurogenesis, astroglial activation, and behaviour in animals with pro-epileptogenic alterations. Methods: Five-month-old Wistar rats were divided into four groups: control (CT), pentylenetetrazol (PTZ), imipenem-treated group (IM), and imipenem after PTZ-kindling (IM-PTZ). Epileptogenesis was induced by PTZ-kindling for 28 days, followed by 10 days of imipenem (40 mg/kg) or saline injections. Rats underwent memory and anxiety tests followed by immunohistochemical analyses of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in the hippocampus. Results: Both kindled groups displayed comparable impairments in spatial learning and working memory, while imipenem alone did not alter behaviour. The IM-PTZ group failed to reach control-level performance only in the final Morris Water Maze acquisition trials, suggesting a deficit in memory consolidation rather than a total loss of retention, as the probe trial remained comparable across all groups. Although PTZ increased anxiety-like behaviour, no locomotor differences were observed in open-field test, confirming cognitive impairments were not due to motor deficits. These behavioural changes mirrored distinct cellular alterations: while PTZ alone triggered a compensatory increase in DCX neuronal density and astrocytic branching, imipenem co-administration suppressed this neurogenic response, bringing DCX to baseline. Furthermore, combined treatment induced an uncoupling of astrocytic response, marked by increased astrocyte density and reduced process complexity in dentate hilus and Cornus Ammonis 3 (CA3). Conclusions: These results suggest that imipenem modulates the cellular substrate of the pre-sensitized brain, interfering with hippocampal plasticity and glial compensatory mechanisms, rather than directly driving further behavioural deterioration.