TY - JOUR
T1 - Perinatal Hypoxic‐Ischemic Brain Injury Enhances Quisqualic Acid‐Stimulated Phosphoinositide Turnover
AU - Chen, Chu‐Kuang ‐K
AU - Silverstein, Faye S.
AU - Fisher, Stephen K.
AU - Statman, Daniel
AU - Johnston, Michael V.
PY - 1988/8
Y1 - 1988/8
N2 - Abstract: In an experimental model of perinatal hypoxic‐ischemic brain injury, we examined quisqualic acid (Quis)‐stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7‐day‐old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis‐stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic‐ischemic injury. The glutamate agonist Quis (10‐4M) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 ± 237% of basal, mean ± SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 ± 134%) and by about sixfold in controls (631 ± 177%, p < 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 ± 157%, 474 ± 89%, and 506 ± 115% (p < 0.05). In contrast, stimulation of PPI turnover elicited by the cho‐linergic agonist carbamoylcholine, (10‐4 or 10‐2M) was unaffected by hypoxia‐ischemia. The results suggest that prior exposure to hypoxia‐ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.
AB - Abstract: In an experimental model of perinatal hypoxic‐ischemic brain injury, we examined quisqualic acid (Quis)‐stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7‐day‐old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis‐stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic‐ischemic injury. The glutamate agonist Quis (10‐4M) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 ± 237% of basal, mean ± SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 ± 134%) and by about sixfold in controls (631 ± 177%, p < 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 ± 157%, 474 ± 89%, and 506 ± 115% (p < 0.05). In contrast, stimulation of PPI turnover elicited by the cho‐linergic agonist carbamoylcholine, (10‐4 or 10‐2M) was unaffected by hypoxia‐ischemia. The results suggest that prior exposure to hypoxia‐ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.
KW - Carbamoylcholine
KW - Hippocampus
KW - Hypoxia‐ischemia
KW - Inositol phospholipids
KW - Perinatal
KW - Quisqualic acid
KW - Striatum
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U2 - 10.1111/j.1471-4159.1988.tb01046.x
DO - 10.1111/j.1471-4159.1988.tb01046.x
M3 - Article
C2 - 2839619
AN - SCOPUS:0023765999
SN - 0022-3042
VL - 51
SP - 353
EP - 359
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -