MetabolismExploiting local measures of glucose metabolism using 2-deoxyglucose techniques, researchers showed that moderate hypothermia (30��C) reduced glucose utilisation compared with normothermia [27]. Metabolic effects of mild hypothermia have also been shown using nuclear magnetic resonance spectroscopy, in which the metabolic effects of different www.selleckchem.com/products/Axitinib.html levels of hypothermia were reported [28]. Therefore, hypothermia lowers metabolic and energy demands, having potentially beneficial effects on cytoplasmic ATP and the maintenance of normal transmembrane ion and neurotransmitter gradients. The magnitude of preservation of ATP levels depends on both the temperature reduction and the severity of the injury. Therefore, an important mechanism for the neuroprotective effects of hypothermia is a reduction or delay in metabolic demand during and after an acute CNS injury.

ExcitotoxicityThe effects of moderate hypothermia on glutamate excitotoxicity were reported using microdialysis to assay extracellular/extravascular concentrations of neurotransmitters after global ischaemia. The middle cerebral artery occlusion model is considered a reasonable model for traumatic hemorrhagic contusion (John Povlishock, personal communication). Busto and colleagues [22] showed that intra-ischaemic hypothermia (33��C and 30��C) attenuated the rise in extracellular levels of glutamate and dopamine after global cerebral ischaemia. These studies have been replicated in a variety of models of ischaemia, indicating that one of the major mechanisms by which temperature affects neuronal vulnerability is through reducing excitotoxicity following cerebral ischaemia [22,29,30].

Delayed pharmacological treatments that reduce excitotoxicity further improve outcome in combination with hypothermia [31] and may be a promising strategy for further studies. The glutamatergic receptors, AMPA (alpha-amino-3-hydroxyl-5- methyl-4-isoxazole-propionate) and NMDA (N-methyl D-aspartate), are also modulated by hypothermia. Expression of hippocampal glutamate receptors is decreased after transient global ischaemia and this is completely blocked by intra-ischaemic hypothermia [32].Other neurotransmitters are also modulated by hypothermia. Lyeth and colleagues [33] demonstrated that hypothermia (30��C) reduced elevations in cerebrospinal levels of acetylcholine after TBI.

Conversely, hypothermia delayed decreases in dopamine, norepinephrine, and serotonin after global cerebral ischaemia [34]. But other studies have demonstrated that hypothermia (32��C) can improve outcome after CNS injury without attenuating extracellular levels of glutamate and aspartate [11,28,35]. The Cilengitide neurotransmitter response, in various injury models, may be temperature-dependent, but attenuating other injury cascades may be more important in delivering possible beneficial effects of hypothermia.Cerebrovascular effectsThe effects of hypothermia on cerebral blood flow are controversial.