Ketanserin reduces neuronal calcium accumulation and cell death in the hippocampus of the Mongolian gerbil after transient forebrain ischemia.
Excessive neuronal activity combined with an increased release of neurotransmitters is supposed to contribute to the delayed neuronal degeneration in animal models of transient cerebral ischemia. Since evidence is accumulating that serotonin (5-HT) exerts an excitatory effect on neurons via 5-HT2 receptors we tested the hypothesis that 5-HT2 receptor antagonists could protect neurons in the gerbil after transient bilateral carotid occlusion. In a first series of experiments, the 5-HT2 receptor antagonist ketanserin was injected intraperitoneally 15 min prior to 5 min of forebrain ischemia and given twice daily on the following 3 days. At a dose of 10 mg/kg i.p., the number of intact hippocampal CA1 neurons was significantly higher than in the saline-treated group and reached 74% of the sham-operated controls. In addition, the degree of neuronal damage correlated with an increased intracellular Ca2+ content in CA1 pyramidal neurons as revealed by arsenazo(III) staining with a procedure modified for paraffin sections. In a second series of experiments, ketanserin (10 mg/kg) was injected at various times after onset of ischemia. Up to a period of 90 min after ischemia, the number of intact CA1 pyramidal cells in ketanserin-treated animals was still significantly higher than in the saline-treated group. These results indicate that 5-HT2 receptor antagonists may protect neurons against ischemic damage even when the treatment is started after onset of ischemia. It remains to be investigated whether the neuroprotective effect of ketanserin is due to a neuronal action or to an inhibition of cerebrovascular vasospasm.
Klisch
J
J
Institute for Neurobiology, Troponwerke, Köln, FRG.
Bode-Greuel
K M
KM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology; D012016:Reference Values
D007650:Ketanserin