Abstract
It is well established that ischemia-induced release of glutamate and the subsequent activation of postsynaptic 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°C, 37°C, or 39°C. Prior to and following ischemia, brain temperature was 37°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°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. In contrast, in rats with hypothermic ischemia (30°C), significant overall effects were noted only for total PKC in thalamus, which showed depressed levels at both 1 and 24 h of recirculation. Rats with hyperthermic (39°C) ischemia also showed significant overall effects for the time course of membrane-bound, cytosolic, and total PKC activities in the hippocampus, striatum, and cortex. However, no significant reductions in PKC indices were observed in the thalamus. For membrane-bound PKC, significant temperature effects were noted for hippocampus, striatum, and cortex, but not for thalamus. For cytosolic, as well as total PKC, activity, significant temperature effects were noted for all four brain regions. Our results indicate that ischemia, followed by reperfusion, induces a significant reduction in PKC activity and that this process is highly influenced by the brain temperature during ischemia. Furthermore, our data also establish that differences exist in the response of PKC to ischemia/recirculation in vulnerable versus nonvulnerable brain regions. These results suggest that PKC alterations may be an important factor involved in the modulatory effects of temperature on the outcome following transient global ischemia.
| Original language | English |
|---|---|
| Pages (from-to) | 1095-1103 |
| Number of pages | 9 |
| Journal | Journal of Neurochemistry |
| Volume | 63 |
| Issue number | 3 |
| State | Published - Sep 1 1994 |
Fingerprint
Keywords
- Cerebral ischemia
- Protein kinase C
- Selective vulnerability
- Temperature
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Regional alterations of protein kinase C activity following transient cerebral ischemia : Effects of intraischemic brain temperature modulation. / Busto, Raul; Globus, Mordecai Y T; Neary, Joseph T.; Ginsberg, Myron.
In: Journal of Neurochemistry, Vol. 63, No. 3, 01.09.1994, p. 1095-1103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regional alterations of protein kinase C activity following transient cerebral ischemia
T2 - Effects of intraischemic brain temperature modulation
AU - Busto, Raul
AU - Globus, Mordecai Y T
AU - Neary, Joseph T.
AU - Ginsberg, Myron
PY - 1994/9/1
Y1 - 1994/9/1
N2 - It is well established that ischemia-induced release of glutamate and the subsequent activation of postsynaptic 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°C, 37°C, or 39°C. Prior to and following ischemia, brain temperature was 37°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°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. In contrast, in rats with hypothermic ischemia (30°C), significant overall effects were noted only for total PKC in thalamus, which showed depressed levels at both 1 and 24 h of recirculation. Rats with hyperthermic (39°C) ischemia also showed significant overall effects for the time course of membrane-bound, cytosolic, and total PKC activities in the hippocampus, striatum, and cortex. However, no significant reductions in PKC indices were observed in the thalamus. For membrane-bound PKC, significant temperature effects were noted for hippocampus, striatum, and cortex, but not for thalamus. For cytosolic, as well as total PKC, activity, significant temperature effects were noted for all four brain regions. Our results indicate that ischemia, followed by reperfusion, induces a significant reduction in PKC activity and that this process is highly influenced by the brain temperature during ischemia. Furthermore, our data also establish that differences exist in the response of PKC to ischemia/recirculation in vulnerable versus nonvulnerable brain regions. These results suggest that PKC alterations may be an important factor involved in the modulatory effects of temperature on the outcome following transient global ischemia.
AB - It is well established that ischemia-induced release of glutamate and the subsequent activation of postsynaptic 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°C, 37°C, or 39°C. Prior to and following ischemia, brain temperature was 37°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°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. In contrast, in rats with hypothermic ischemia (30°C), significant overall effects were noted only for total PKC in thalamus, which showed depressed levels at both 1 and 24 h of recirculation. Rats with hyperthermic (39°C) ischemia also showed significant overall effects for the time course of membrane-bound, cytosolic, and total PKC activities in the hippocampus, striatum, and cortex. However, no significant reductions in PKC indices were observed in the thalamus. For membrane-bound PKC, significant temperature effects were noted for hippocampus, striatum, and cortex, but not for thalamus. For cytosolic, as well as total PKC, activity, significant temperature effects were noted for all four brain regions. Our results indicate that ischemia, followed by reperfusion, induces a significant reduction in PKC activity and that this process is highly influenced by the brain temperature during ischemia. Furthermore, our data also establish that differences exist in the response of PKC to ischemia/recirculation in vulnerable versus nonvulnerable brain regions. These results suggest that PKC alterations may be an important factor involved in the modulatory effects of temperature on the outcome following transient global ischemia.
KW - Cerebral ischemia
KW - Protein kinase C
KW - Selective vulnerability
KW - Temperature
UR - http://www.scopus.com/inward/record.url?scp=0027932931&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027932931&partnerID=8YFLogxK
M3 - Article
C2 - 8051550
AN - SCOPUS:0027932931
VL - 63
SP - 1095
EP - 1103
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -