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 receptor activation and subsequent elevation of intracellular Ca2+ concentration. 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 mongolian gerbil after global ischemic insults. The number of PV-immunoreactive (PV-ir) neurons in CA1 were significantly decreased from 1 day after cerebral ischemia, while dizocilpine pretreatment completely suppressed the loss of PV-ir neurons in CA1. Dizocilpine pretreatment also protected the structural loss of microtubule-associated protein 2 immunoreactivity in CA1 after 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-defined cellular activity of PV-ir neurons was slightly increased by dizocilpine pretreatment in the hippocampal area. This study demonstrated that NMDA receptor mediated calcium influx was associated with the loss of PV-ir neurons in CA1 hippocampal region, and that dizocilpine pretreatment increased Fos expression and the neuronal activity of PV-ir neurons in the non-vulnerable region of hippocampus after cerebral ischemia. Based on this data, we conclude that the protective effect of dizocilpine may be induced by the regulation of calcium overload, or by the upregulation of a neuroregenerative initiator such as Fos protein.
Kwon
Y B
YB
Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, Suwon, South Korea.
Yang
I S
IS
Kang
K S
KS
Han
H J
HJ
Lee
Y S
YS
Lee
J H
JH
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002021:Buffers; D002118:Calcium / Q000502:physiology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D010320:Parvalbumins / Q000276:immunology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*
D002021:Buffers; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D010320:Parvalbumins; D016760:Proto-Oncogene Proteins c-fos; D016291:Dizocilpine Maleate; D002118:Calcium