Hypoxic modulation of striatal lesions induced by administration of endothelin-1.
Levels of endothelin-1 (ET-1), a potent endogenous vasoconstrictor, are elevated in plasma and cerebrospinal fluid (CSF) following cerebral ischemia and reperfusion injury. The present study sought insight into the potential differential vasoactive effects on the cerebral vasculature and resultant neural damage of ET-1 during normoxic vs. ischemic conditions and upon reperfusion. Under normoxic conditions, intrastriatal stereotaxic injection of exogenous ET-1 (40 pmol) induced a significant (P<0.05) reduction (</=29+/-12%) in the regional (striatal) cerebral blood flow measured by Laser Doppler flowmetry (CBF(LDF)) for up to 40 min in halothane-anesthetized male Long-Evans rats. Intrastriatal injection of ET-1 10 min after the onset of hypoxia (12% O(2), balance N(2)) tended to blunt, but not significantly, the striatal CBF(LDF) responses to the 35 min period of hypoxia. ET-1 given during reoxygenation significantly (P<0.05) reduced striatal CBF(LDF), which was similar to the effect of ET-1 during normoxia. ET-1-induced infarction when administered prior to hypoxia, but not during or post-hypoxia, was significantly (P<0.05) exacerbated compared to infarction of ET-1 without hypoxia. These results suggest that exogenous ET-1 administered into the brain parenchyma can induce an infarction associated with modulation of CBF(LDF) during the normoxic or reoxygenation period, but not during the hypoxic period and that the increased release of ET-1 in any pathological phase of cerebral ischemia contributes to irreversible neural damage with associated hemodynamic disturbances.
Park
L
L
Department of Physiology and Saskatchewan Stroke Research Center, University of Saskatchewan, 107 Wiggins Road, Saskatoon, S7N 5E5, Saskatchewan, Canada. park@duke.usask.ca
Thornhill
J
J
D000818:Animals; D002544:Cerebral Infarction / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology*; D019332:Endothelin-1 / Q000494:pharmacology*; D000860:Hypoxia / Q000473:pathology*; D007267:Injections; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012016:Reference Values
D019332:Endothelin-1; D010100:Oxygen