Ampicillin, a
beta-lactam antibiotic, has been reported to induce astrocytic
glutamate transporter-1 which plays a crucial role in protecting neurons against
glutamate excitotoxicity. We investigated the effect of
ampicillin on neuronal damage in the mouse hippocampus and neostriatum following transient global forebrain
ischemia. Male C57BL/6 mice were anesthetized with
halothane and subjected to bilateral occlusion of the common carotid artery for 40 min.
Ampicillin was administered post-ischemically (for 3 days) and/or pre-ischemically (for 3~5 days until one day before the onset of
ischemia). Pre- and post-ischemic treatment with
ampicillin (50 mg/kg/day or 200 mg/kg/day) prevented ischemic neuronal death in the medial CA1 area of the hippocampus as well as the neostriatum in a dose-dependent manner. In addition, ischemic neuronal damage was reduced by pre-ischemic treatment with
ampicillin (200 mg/kg/day). In summary, our results suggest that
ampicillin plays a functional role as a chemical preconditioning agent that protects hippocampal neurons from ischemic insult.