Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]-carbonyl]-L-histidyl-L-prolinamide dihydrate), a new thyrotropin releasing hormone (TRH) analogue, on morphine-induced hypothermia, development of cerebral ischemia and analgesia was investigated in rodents. YM-14673, in doses not affecting the normal rectal temperature, antagonized morphine-induced hypothermia in mice. Morphine-induced hypothermia was also antagonized by administration of TRH, in doses increasing normal rectal temperature. Morphine increased the appearance rate of convulsions in rats subjected to bilateral occlusion of the carotid artery. YM-14673, unlike TRH, reduced the appearance rate of convulsions increased by morphine in the ischemic rats. Morphine-induced analgesia measured by the hot plate method was not affected by both YM-14673 and TRH. Naloxone antagonized the effect of morphine in the 3 models. These results suggest that YM-14673 possesses physiological opioid antagonistic properties.
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PMID:Effects of YM-14673, a new TRH analogue, on responses to morphine in rodents. 251 20

Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of CBF over several hours. Morphine and the opiate antagonist, naloxone, were tested for their effects on the reactive hyperemia that follows a brief anoxic challenge. Morphine (5.0 mg/kg) significantly reduced the peak increase in flow during the hyperemia and, at both of the doses used (1.0 and 5.0 mg/kg), caused a small, nonsignificant increase in the duration of the reactive hyperemia. Naloxone (0.1 and 1.0 mg/kg) enhanced basal CBF rates and significantly prolonged the duration of the reactive hyperemia. These effects of naloxone may account for its beneficial effects in the treatment of cerebral ischemia.
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PMID:Naloxone enhances cerebral reactive hyperemia in the rat. 405 95

The effects of an opiate agonist (morphine) and antagonist (naloxone) on neurologic function in conditions of acute and subacute focal cerebral ischemia were tested in a baboon model. Fourteen baboons (Papio papio) underwent unilateral transorbital microsurgical occlusion of the middle cerebral artery (MCA). Blood pressure, heart rate and core temperature were monitored continuously; frequent arterial blood gas measurements were made. Cardiac output, cardiac filling pressures, and regional cerebral blood cross-flow were measured in selected baboons. Naloxone administered intravenously consistently reversed hemiparesis and hemiplegia in all baboons for as long as they lived (4 h to 8 days postocclusion). Morphine administered intravenously converted hemiparesis to hemiplegia; this effect was naloxone-reversible. There were no significant changes in any parameter measured after the administration of either drug. Phenylephrine (used to elevate mean arterial pressure to 20 mm higher than the highest pressure measured after naloxone administration) and isoproterenol (used to elevate cardiac output to 1 l/min higher than the highest value measured after naloxone administration) produced no change in neurologic function. It appears that naloxone can reverse, and morphine exacerbate, focal ischemic neurologic deficits produced in baboons by MCA occlusion. The observed changes in neurologic function are not associated with or mediated by alterations in core temperature or cardiopulmonary functions.
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PMID:Naloxone reversal and morphine exacerbation of neurologic deficits secondary to focal cerebral ischemia in baboons. 669 45

The present study was designed to investigate the possible role of opioids and K(ATP) channels in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion (I/R) induced neuronal injury. Mice were subjected to global ischemia by bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h, to produce neuronal injury. Ischemic postconditioning was induced by three episodes of carotid artery occlusion and reperfusion of 10 s each, immediately after global ischemia. Morphine postconditioning was induced by administration of morphine (5 mg/kg i.v.), 5 min prior to reperfusion. Naloxone (5 mg/kg i.v.), opioid receptor antagonist, and glibenclamide (5 mg/kg i.v.), K(ATP) channel blocker were administered 10 min before global ischemia. Extent of cerebral injury was assessed by measuring cerebral infarct size using triphenyl tetrazolium chloride (TTC) staining. Short-term memory was evaluated using the elevated plus maze test, while degree of motor incoordination was evaluated using inclined beam-walking, rota-rod and lateral push tests. Bilateral carotid artery occlusion followed by reperfusion resulted in significant increase in infarct size, impairment in short-term memory and motor co-ordination. Ischemic/morphine postconditioning significantly attenuated I/R induced neuronal injury and behavioural alterations. Pretreatments with naloxone and glibenclamide attenuated the neuroprotective effects of ischemic/morphine postconditioning. It may be concluded that ischemic/morphine postconditioning protects I/R induced cerebral injury via activating opioid receptor and K(ATP) channel opening.
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PMID:Possible role of opioids and KATP channels in neuroprotective effect of postconditioning in mice. 1875 72

The signaling pathway of chronic morphine treatment to prevent neuronal damage following transient cerebral ischemia is not clear. In this study, we examined the role of mammalian target of rapamycin (mTOR) to identify the neuroprotective effects of chronic morphine preconditioning on the hippocampus following ischemia-reperfusion (I/R) injury. Morphine was administered for 5 days, twice a day, before inducing I/R injury. The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. The passive avoidance test was used to evaluate memory performance. Neuronal density and apoptosis were measured in the CA1 region, 72 h after I/R injury. The expressions of mTOR and phosphorylated mTOR (p-mTOR), as well as superoxide dismutase (SOD) activity were determined 24 h after I/R injury. Chronic morphine treatment attenuated apoptosis and neuronal loss in the hippocampus after I/R injury, which led to improvement in memory (P < 0.05 vs. untreated I/R) and increase in the expression of p-mTOR (P < 0.05 vs. untreated I/R) and SOD activity (P < 0.05 vs. untreated I/R) in the hippocampus. Pretreatment with rapamycin abolished all the above-mentioned protective effects. These results describe novel findings whereby chronic morphine preconditioning in hippocampal CA1 neurons is mediated by the mTOR pathway, and through increased phosphorylation of mTOR can alleviate oxidative stress and apoptosis, and eventually protect the hippocampus from I/R injury.
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PMID:Preconditioning with morphine protects hippocampal CA1 neurons from ischemia-reperfusion injury via activation of the mTOR pathway. 2888 Nov 54