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Kinetics of microcirculatory, NAD/NADH, and electrocorticographic changes in cat brain cortex during ischemia and recirculation
Author(s) -
Dora Eors,
Tanaka Kartaro,
Greenberg Joel H.,
Gonatas Nicholas H.,
Reivich Martin
Publication year - 1986
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410190604
Subject(s) - ischemia , nad+ kinase , anesthesia , cortical spreading depression , microcirculation , middle cerebral artery , cerebral blood flow , medicine , occlusion , redox , cats , cerebral cortex , chemistry , biochemistry , enzyme , organic chemistry , migraine
Changes in microcirculation, the NAD/NADH redox state, and electrical activity during 2 hours of ischemia and 4 hours of reperfusion produced by middle cerebral artery occlusion and release were studied in cats. Twelve animals were classified into three groups of ischemia (mild, moderate, and severe) based on the severity of electrocorticographic (ECoG) depression at the end of the recovery period. Four animals were studied as controls. Occlusion of the middle cerebral artery (MCAO) resulted in a marked but similar degree of reduction in cerebral blood flow (CBF) in all three groups. After this initial change, CBF increased continuously during occlusion in the mild group. CBF in the moderate and severe groups remained at the same low level during the entire period of MCAO. Immediately after MCAO, NAD reduction was increased by approximately 50% in all groups. At the end of MCAO, while the NAD/NADH redox state returned to its pre‐ischemic reference level in the severe group, it remained markedly reduced in the mild and moderate groups. Removal of the clip led to slight reactive hyperemia in the mild and severe groups but not in the moderate group. Immediately after recirculation, NAD/NADH redox was shifted toward oxidation in all groups. However, this reoxidation of NADH was only partial in the mild and moderate groups, and a pronounced hyperoxidation occurred in the severe group. In spite of the similar behavior of CBF in the recovery period, a marked secondary NAD reduction occurred in the moderate group during the recirculation period. It is suggested that this represents cessation of mitochondrial electron transport in the dying cells, accompanied by stimulated anaerobic glycolysis in other cells. The spontaneous oxidation of NADH during MCAO and its hyperoxidation during recirculation in the severe group may be due to an insufficient supply of reducing equivalents into the mitochondria and/or the release of oxidizing substances in the brain.