Neuroprotection by MK-801 following cerebral ischemia in Mongolian gerbils

Abstract

Global cerebral ischemia in Mongolian gerbils is an established model in experimental research on cerebral ischemia, which is characterized morphologically by selective neuronal damage in the hippocampus, striatum, and cortex. Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of dizocilpine malate (MK-801), a non-competitive glutamate antagonist, in the model of 10-min gerbil cerebral ischemia. Gerbils were given MK-801 (3 mg/kg i.p.) or saline immediately after the occlusion. On day 4 after reperfusion, neuronal damage was examined in the hippocampus (30 μm) and striatum slices (5 μm) stained with hematoxylin/eosin, fluorescent Nissl staining and membrane tracer DiI. The striatum and C3 regions of the hippocampus were analyzed by confocal microscopy. Neuroprotection was determined by quantifying the degree of cell loss, reduction of morphologically damaged cells, and the degree of preservation of recognizable neuroanatomical pathways after the ischemic insult. Our results demonstrate that the neuronal damage induced by sustained ischemia is related to abnormalities in glutamatergic function associated with NMDA receptors. MK-801 significantly prevented neuronal loss in the tested brain structures. All of this contributes to a better understanding of the given pathophysiological process causing ischemic neuronal damage.