NADH fluorescence and regional energy metabolites during focal ischemia and reperfusion of rat brain.
Transient focal ischemia was produced in rat brain using simultaneous, reversible occlusion of the middle cerebral artery (MCA) and both carotid arteries. NADH tissue fluorescence and regional levels of ATP and lactate were measured after occlusion for 1 or 2.5 h and after reperfusion for 1 or 24 h following a 2.5-h insult. Occlusion for 1 or 2.5 h caused a marked but microheterogenous increase in NADH fluorescence, which was restricted to the MCA territory of the ipsilateral cortex. In this ischemic core, tissue levels of ATP were nearly depleted, while lactate accumulated to 10-13 mmol/kg. Metabolic alterations were less pronounced in regions adjacent to the ischemic core; however, one border region experienced a progressive increase in lactate between 1 and 2.5 h. NADH fluorescence and metabolite levels were not significantly altered in subcortical structures. In animals reperfused after a 2.5-h insult, NADH fluorescence diminished in the ischemic core to abnormally low levels, ATP was restored only to 37-50% of control, and lactate remained elevated. By 24 h, histologic infarction was evident in the regions with metabolic impairment. These results indicate that focal depletion of energy metabolites for 2.5 h caused irreversible impairment of energy metabolism and focal infarction even though lactate accumulation was moderate.
Welsh
F A
FA
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia.
Marcy
V R
VR
Sims
R E
RE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000378:metabolism; D004734:Energy Metabolism; D005453:Fluorescence; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009243:NAD / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
D007773:Lactates; D009243:NAD; D019344:Lactic Acid; D000255:Adenosine Triphosphate