Effects of dizocilpine pretreatment on parvalbumin immunoreactivity and Fos expression after cerebral ischemia in the hippocampus of the mongolian gerbil

The mechanisms of ischemic neuronal death have been focused on glutamate re ceptor activation and subsequent elevation of intracellular Ca2+ concentrat ion. The purpose of this study was to evaluate the effects of dizocilpine, an NMDA receptor antagonist, pretreatment on Fos expression and parvalbumin (PV, calcium binding protein) immunoreactivity in the hippocampus of the m ongolian gerbil after global ischemic insults. The number of PV-immunoreact ive (PV-ir) neurons in CA1 were significantly decreased from 1 day after ce rebral ischemia, while dizocilpine pretreatment completely suppressed the l oss of PV-ir neurons in CA1. Dizocilpine pretreatment also protected the st ructural loss of microtubule-associated protein 2 immunoreactivity in CA1 a fter ischemic insults. In addition, dizocilpine pretreatment increased Fos expression in both hippocampal CA3 and CA4 after 3 hr ischemic reperfusion as compared to that of the saline pretreated group. Subsequently, the Fos-d efined cellular activity of PV-ir neurons was slightly increased by dizocil pine pretreatment in the hippocampal area. This study demonstrated that NMD A receptor mediated calcium influx was associated with the loss of PV-ir ne urons in CA1 hippocampal region, and that dizocilpine pretreatment increase d Fos expression and the neuronal activity of PV-ir neurons in the non-vuln erable region of hippocampus after cerebral ischemia. Based on this data, w e conclude that the protective effect of dizocilpine may be induced by the regulation of calcium overload, or by the upregulation of a neuroregenerati ve initiator such as Fos protein.