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

Increases in extracellular glutamate during cerebral ischemia may play an important role in neuronal injury. Lubeluzole is a novel neuroprotective drug, which in previous in vitro and focal ischemia studies has been shown to inhibit nitric oxide synthesis, to block voltage-gated Na+-ion channels, and to inhibit glutamate release. In this study, we investigated the ability of lubeluzole to inhibit glutamate accumulation during episodes of transient global cerebral ischemia. Twenty-five New Zealand white rabbits were randomized to one of four groups: a normothermic control group; a hypothermic group; a 1.25 mg/kg lubeluzole group; or a 2.5 mg/kg lubeluzole group. The animals were anesthetized, intubated, and ventilated before microdialysis probes were placed in the hippocampus. Lubeluzole was given intravenously 90 min before the onset of ischemia. Esophageal temperature was maintained at 38 degrees C in the control, and lubeluzole treated groups, while the animals in the hypothermia group were cooled to 30 degrees C. A 15-min period of global cerebral ischemia was produced by inflating a neck tourniquet. Glutamate concentrations in the microdialysate were determined using high-performance liquid chromatography (HPLC). During ischemia and early reperfusion, glutamate concentrations increased significantly in the control group and returned to baseline after 15 min of reperfusion. In the lubleuzole 2.5 mg/kg and hypothermia groups, glutamate levels were significantly lower (P<0.05) than in the control group and there was no significant change from baseline levels during the entire experiment. This study suggests that lubeluzole is effective in inhibiting extracellular glutamate accumulation during global cerebral ischemia, and has the potential to produce potent neuroprotection when instituted prior to an ischemic event.
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PMID:Lubeluzole inhibits accumulation of extracellular glutamate in the hippocampus during transient global cerebral ischemia. 1130 16

Considerable effort and substantial funding has gone towards the development of a neuroprotective agent that could be given after brain trauma to reduce mortality and improve functional recovery. There have been many failed or inconclusive studies to date. In Europe two promising studies have been stopped or shelved (Lubeluzole, Janssen-Cilag and BAYx3702, Bayer) and the future of pharmacological neuroprotection after traumatic brain injury is in doubt. Clinicians managing patients with a head injury are therefore left with the detection and prevention of secondary insults to the brain, including the management of medical complications of brain injury, and non-pharmaceutical interventions that might beneficially modify the brain's response to trauma. Of the potential interventions, moderate hypothermia is the most promising.
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PMID:Head injury: complications and management. 1701 60