Indexed on: 01 Oct '94Published on: 01 Oct '94Published in: Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid
We investigated the effect of beraprost sodium (BPS), a new prostacyclin analog, and dizocilpine (MK-801) on repeated ischemia-induced cerebral atrophy and chronic cortical neuronal loss in gerbils. The left common carotid artery of gerbils was repeatedly occluded (for 10, 7, 7, and 7 min) at intervals of 24 h. The thickness of the cerebral cortex of the ischemic hemisphere diminished with increasing time of reperfusion after an ischemic insult. The animals were given BPS (1–100 μg/kg, po) or MK-801 (3–300 μg/kg, sc) after the first ischemic insult, and then twice daily for 4 wk. Increases in the amount of neuronal loss and acidophilic neurons, and progressive atrophy were observed with increasing time of reperfusion in the cerebral cortex of the ischemic hemisphere. Cortical sections revealed no astrocytes positive for glial fibrillary acidic protein (GFAP), whereas the hippocampal CA1 area showed neuronal loss accompanied by GFAP-positive astrocytes. In control animals at 4 wk survival, the area ratio neurons ratio (number of neurons in ischemic cortex/number of neurons in opposite cortex) were 89.8±3.0% and 74.6±3.4%, respectively. BPS was found to inhibit atrophy and chronic cortical neuronal loss in the ischemic hemisphere in a dose-dependent manner, whereas MK-801 showed no inhibitory effects at any dose tested. These results may suggest that the nature of neuronal degeneration differs between the cortical and hippocampal areas, that cortical neuronal degeneration might not involve glutamtate pathways with NMDA receptors in this model, and that prostacyclin could play an essential role in prevention of ischemia-induced progressive neuronal loss.