A concerted role of Na|[plus]||[ndash]|K|[plus]||[ndash]|Cl|[minus]| cotransporter and Na|[plus]||[sol]|Ca2|[plus]| exchanger in ischemic damage
Journal of Cerebral Blood Flow and Metabolism(2008)
Abstract
Na+–K+–Cl− cotransporter isoform 1 (NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (~116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+ exchanger isoform 1 heterozygous (NCX1+/−) neurons with ~50% less of NCX1 protein exhibited ~64% reduction in NCX-mediated Ca2+ influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/−/NKCC1+/−) neurons. NCX-mediated Ca2+ influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ~80% mortality rate in NCX1+/+ neurons and in NCX1+/− neurons. In contrast, NKCC1+/− neurons exhibited ~45% less cell death. The lowest mortality rate was found in NCX1+/−/NKCC1+/− neurons (~65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1+/−/NKCC1+/− brains after transient cerebral ischemia. NCX1+/−/NKCC1+/− mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.
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Key words
neurovascular, brain, neurology, neuroscience, blood, brain circulation, brain metabolism, cerebrovascular, JCBFM, nature journals, nature publishing group, ISCBFM
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