In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion.
An increase in cytosolic free calcium concentration ([Ca2+]i) may trigger irreversible cell injury following cerebral ischemia. We have measured changes in [Ca2+]i in cat cortex in vivo during ischemia produced by 1 hour of middle cerebral artery occlusion and during 30 minutes of reperfusion. Indo-1, a fluorescent Ca2+ indicator, was loaded into the exposed cortex by superfusion, and changes in the [Ca2+]i signal (400/506 nm ratio) were measured microfluorometrically during ultraviolet excitation (340 nm). The nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) redox state and hemodynamic changes were measured simultaneously. The animals showing severe deterioration in their electroencephalograms (EEG) showed a progressive increase in the [Ca2+]i signal during ischemia (baseline: 1.46 +/- 0.05; 60 minutes after occlusion: 2.99 +/- 0.37; n = 7). At 30 minutes following reperfusion, the animals showing little recovery in their EEG exhibited a further increase in [Ca2+]i (4.71 +/- 0.87, n = 3), whereas animals showing significant recovery in their EEG also showed recovery of [Ca2+]i (1.55 +/- 0.09, n = 4). By contrast, the moderate or mild stroke animals with less deterioration in their EEGs showed no increase in [Ca2+]i during either ischemia or reperfusion. These data suggest that the increase in [Ca2+]i might be closely related not only to deterioration of brain function during ischemia but also to poor recovery during the reperfusion period.
Uematsu
D
D
Department of Neurology, University of Pennsylvania, Philadelphia, 19104.
Greenberg
J H
JH
Reivich
M
M
Karp
A
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002415:Cats; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D007211:Indoles; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000097:blood; D012016:Reference Values; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D001786:Blood Glucose; D005456:Fluorescent Dyes; D007211:Indoles; D002245:Carbon Dioxide; C048960:indo-1; D010100:Oxygen; D002118:Calcium