Altered expression of sodium transporters in ischemic penumbra after focal cerebral ischemia in rats.
This study was aimed to examine whether the changes of protein expression of sodium transporters in the ischemic penumbra are associated with the pathogenesis of ischemia-induced brain edema and/or brain cell injury. An experimental model of cerebral ischemia was made by permanent middle cerebral artery occlusion (pMCAO) in rats and the changes of protein expression of sodium transporters in the ischemic penumbra were examined by immunoblotting. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 3 and 6h after pMCAO. Immunoblotting analyses revealed significantly increased expressions of electrogenic NBC (241 +/- 11% at 3 h and 154 +/- 9% at 6 h, P < 0.05) and NHE1 (144 +/- 3% at 3 h and 170 +/- 9% at 6 h, P < 0.05), compared with sham-operated controls. In contrast, Na-K-ATPase expression (78 +/- 6% at 3 h and 85 +/- 3% at 6 h, P < 0.05) was significantly decreased. The expression of NCX1 was unchanged at 3 h, but was significantly increased at 6 h (141 +/- 3%, P < 0.05). In addition, the expressions of neuronal (NeuN) and astroglial cell (GFAP) proteins were decreased, whereas the expression of oligodendrocyte protein (CNPase) was unchanged. Taken together, the selectively increased expressions of NHE1, electrogenic NBC, and NCX1 and decreased expression of Na-K-ATPase in the ischemic penumbra are likely to contribute to the secondary brain cell damages presumably through intracellular Na(+) accumulation, cell swelling, and intracellular Ca(2+) overload.
Department of Anatomy, College of Medicine, Dongguk University, Kyungju 780-714, Republic of Korea.
Yong-Wook
YW
Jung
In-Jang
IJ
Choi
Tae-Hwan
TH
Kwon
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism / Q000503:physiopathology; D054022:Cerebrum / Q000378:metabolism* / Q000503:physiopathology; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015151:Immunoblotting; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C422004:Slc4a4 protein, rat; C452850:Slc9a1 protein, rat; D027982:Sodium-Bicarbonate Symporters; D019831:Sodium-Calcium Exchanger; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C110374:sodium-calcium exchanger 1; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium