Neurochemical correlates of selective neuronal loss following cerebral ischemia: role of decreased Na+,K(+)-ATPase activity.
In order to investigate the role of Na+,K(+)-ATPase in the development of neuronal necrosis following cerebral ischemia, ischemia was induced in gerbils by occluding the common carotid artery unilaterally for 10 min. A time-course analysis revealed that significant reductions of the Na+,K(+)-ATPase activity in the cerebral cortex and hippocampus were manifested at 15 min, 30 min, and 1 h, and returned to the control level one day following recirculation. No apparent alterations of the Mg(2+)-ATPase activity, on the other hand, were obtained throughout the experimental period. Furthermore, Scatchard analyses of [3H]ouabain binding to the cerebral cortex membranes disclosed that the Bmax values invariably decreased without any change of Kd values following ischemia. It has also been shown that treatment of the animals with an agent known to mitigate ischemic neuronal necrosis, i.e. BY-1949, significantly reversed such derangements. These results suggest that the recovery of decreased Na+,K(+)-ATPase activity shortly after ischemia exerts a protective effect against ischemic brain damage.
Nagafuji
T
T
Neuroscience Research Unit, Chugai Pharmaceutical Company Ltd., Shizuoka, Japan.
Koide
T
T
Takato
M
M
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003989:Dibenzoxazepines / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology; D007700:Kinetics; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010042:Ouabain / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D003989:Dibenzoxazepines; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C013983:vinpocetine; D010042:Ouabain; C058844:3-methoxy-11-methyldibenz(b,f)oxazepine-8-carboxylate; D017301:Ca(2+) Mg(2+)-ATPase