Additive neuroprotective effect of Ketanserin and Ipsapirone on the hippocampal damage after transient forebrain ischemia in the Mongolian gerbil

Modulation of the serotonin (5HT) system via 5HT1A or 5HT2A receptors exerts a neuroprotective effect on delayed neuronal death after transient forebrain ischemia. We tested the hypothesis that a 5HT1A agonist (Ipsapirone) in combination with a 5HT2A receptor antagonist (Ketanserin) could improve the neuroprotection. Starting 15 min prior to transient forebrain ischemia in the gerbil model, different doses of Ipsapirone (1, 2, 3 mg) and Ketanserin (5 mg/kg) were applied intraperitoneally. Seven days after ischemia, surviving pyramidal cells of the CA1 sector of the hippocampus were counted. The significance of the differences between the means was assessed by an analysis of variance according to the Scheffé test. The hippocampal cell damage was analyzed by histological evaluation. Combined application of Ipsapirone and Ketanserin led to a dose-dependent additive effect with up to 83% preservation of hippocampal CA1 neurons (P<0.001). The results of the present study suggest that the combination of 5HT1A receptor agonists and 5HT2A receptor antagonists might be an effective tool for the treatment of cerebral ischemia.