Regional alterations of protein kinase C activity following transient cerebral ischemia: effects of intraischemic brain temperature modulation.
It is well established that ischemia-induced release of glutamate and the subsequent activation of post-synaptic glutamate receptors are important processes involved in the development of ischemic neuronal damage. Moderate intraischemic hypothermia attenuates glutamate release and confers protection from ischemic damage, whereas mild intraischemic hyperthermia increases glutamate release and augments ischemic pathology. As protein kinase C (PKC) is implicated in neurotransmitter release and glutamate receptor-mediated events, we evaluated the relationship between intraischemic brain temperature and PKC activity in brain regions known to be vulnerable or nonvulnerable to transient global ischemia. Twenty minutes of bilateral carotid artery occlusion plus hypotension were induced in rats in which intraischemic brain temperature was maintained at 30 degrees C, 37 degrees C, or 39 degrees C. Prior to and following ischemia, brain temperature was 37 degrees C in all groups. Cytosolic, membrane-bound, and total PKC activities were determined in hippocampal, striatal, cortical, and thalamic homogenates at the end of ischemia and at 0.25-24 h of recirculation. PKC activity of control rats varied by region and were affected by altered brain temperature. For both membrane-bound and cytosolic PKC, there was a significant temperature effect, and for membrane-bound PKC there was also a significant effect of region. Rats with normothermic ischemia (37 degrees C) showed extensive depressions of all PKC fractions. Hippocampus and striatum were noteworthy for depressions in PKC activity extending from the earliest (15 min) to the latest (24 h) recirculation times studied, whereas cortex showed PKC depressions chiefly during the first hour of recirculation, and the thalamic pattern was inconsistent.(ABSTRACT TRUNCATED AT 250 WORDS)
Busto
R
R
Department of Neurology, VA Medical Center, University of Miami School of Medicine, Florida 33101.
Globus
M Y
MY
Neary
J T
JT
Ginsberg
M D
MD
D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013788:Thalamus / Q000201:enzymology
D011493:Protein Kinase C