Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia. 783 34

Selective neuronal cell death in the CA1 pyramidal cells of the hippocampus and neurons of the dorsolateral striatum as a consequence of brain ischemia/reperfusion (IR) can be ameliorated with brain hypothermia. Since postischemic injury is mediated partially by chemical production of reactive oxygen species (ROS), decreased ROS production may be one of the mechanisms responsible for cerebral protection by hypothermia. To determine if ischemic brain temperature alters ROS production, reversible IR was produced in rats by occlusion of both carotid arteries with hemorrhagic hypotension. After 15 min of ischemia, circulation was restored for 60 min. Brain temperature was maintained during ischemia at either 30, 36, or 39 degrees C and kept at 36-37 degrees C after reperfusion. Using cerebral microdialysis, we measured nonenzymatic hydroxylation of salicylate by HPLC with electrochemical detection in the hippocampus. CBF was also compared among the groups during IR. The results were that normothermic animals during reperfusion had persistently increased levels of the salicylate hydroxylation product, 2,3-dihydroxybenzoic acid (2,3-DHBA), reaching 251% of control at 60 min. This increase in 2,3-DHBA production was potentiated after 60 min of reperfusion (406% of control) with ischemic hyperthermia. In hypothermic ischemia, 2,3-DHBA production at 60 min was attenuated to 160% of control. CBF decreased to approximately 5% of baseline value during ischemia, but increased three- to four-fold relative to control in all three groups. Therefore, the effects of ischemic brain temperature on 2,3-DHBA production did not correlate with changes in CBF during IR. We conclude that brain-temperature-related changes in OH.production are readily detected in the rat and decreased ROS generation may contribute to cerebral protection afforded by hypothermia during brain ischemia.
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PMID:Brain temperature alters hydroxyl radical production during cerebral ischemia/reperfusion in rats. 853 May 42

Previously, we showed that treatment with resuscitative, post-ischaemic mild hypothermia (34 degrees C for 2 h) reduced apoptosis in the penumbra (cortex), but not in the core (striatum) of an endothelin-1 (Et-1)-induced focal cerebral infarct in the anaesthetized rat. Therefore, the purpose of this study was to investigate by which pathways resuscitative mild hypothermia exerts its neuroprotective effect in this model. The amino acids glutamate, serine, glutamine, alanine, taurine, arginine and the NO-related compound citrulline were sampled from the striatum and cortex of the ischaemic hemisphere using in vivo microdialysis. The in vivo salicylate trapping method was applied for monitoring hydroxyl radical formation via 2,3 dihydroxybenzoic acid (2,3 DHBA) detection. Caspase-3, neuronal nitric oxide synthase (nNOS) immunoreactivity and the volume of ischaemic damage were determined 24 h after the insult. In both the striatum and the cortex, Et-1-induced increases in glutamate, taurine and alanine were refractory to mild hypothermia. However, mild hypothermia significantly attenuated the ischaemia-induced 2,3 DHBA levels and the nNOS immunoreactivity in the cortex, but not in the striatum. These observations were associated with a decreased caspase-3 immunoreactivity. These results suggest that mild hypothermia exerts its neuroprotective effect in the penumbra partially by reducing nNOS activity and thereby preventing oxidative stress. Furthermore, we confirm our previous findings that the neuroprotective effect of resuscitative hypothermia is not mediated by changes in ischaemia-induced amino acid release as they could not be associated with the ischaemia-induced damage in the Et-1 rat model.
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PMID:Post-ischaemic mild hypothermia inhibits apoptosis in the penumbral region by reducing neuronal nitric oxide synthase activity and thereby preventing endothelin-1-induced hydroxyl radical formation. 1619 Aug 88