Previous studies have shown that asphyxia-induced cerebral neurotoxicity is regionally specific. The present study tests the hypothesis that regional differences in cerebral Na+,K+-ATPase activity contribute to heterogeneous regional vulnerability to asphyxial events. Eight newborn piglets (3-5 days old) were exposed to 7 repeated episodes of asphyxia: 3 min cessation of ventilation followed by 15 min reventilation with 21% oxygen(n=3) or with 100% oxygen (n=5). Five normoxic piglets served as controls. Striata and cerebral cortex were removed and liquid-N2 frozen for Na+,K+-ATPase activity measurement. Control Na+,K+-ATPase from membrane preparations was 41±3μmoles Pi/mg protein/hr (mean±SD) for cerebral cortex and 27±3 for striatum. Seven repeated asphyxias followed by 21% oxygen recovery significantly decreased (p<0.01) cortical Na+,K+-ATPase activity to 28±4 (↓32%) while striatal activity was unchanged at 27±3. Similarly, 7 asphyxias followed by reventilation with 100% oxygen decreased cortical Na+,K+-ATPase to 25±5 (↓39%) while striatal Na+,K+-ATPase remained 29±2. Na+,K+-ATPase dysfunction can disrupt nerve cell integrity as well as interrupt neural transmission, leading to neuronal injury and death. The data show higher baseline cortical Na+,K+-ATPase activity which increases cerebral cortical vulnerability to asphyxia, compared to striatum. Striatal Na+,K+-ATPase activity was thus maintained with the present experimental protocol while cortical Na+,K+-ATPase decreased. Post-asphyxial reventilation with 100% compared to 21% oxygen neither attenuated nor exacerbated cortical Na+,K+-ATPase dysfunction. (Funded by NIH-HD20337, MOD-6FY94-0135, UCP-R50693).
