Therapeutic hypothermia in experimental models of focal and global cerebral ischemia and intracerebral hemorrhage.
Experimental evidence shows that therapeutic hypothermia (TH) protects the brain from cerebral injury in multiple ways. In different models of focal and global cerebral ischemia, mild-to-moderate hypothermia reduces mortality and neuronal injury and improves neurological outcome. In models of experimental intracerebral hemorrhage (ICH), TH reduces edema formation but does not show consistent benefi cial effects on functional outcome parameters. However, the number of studies of hypothermia on ICH is still limited. TH is most effective when applied before or during the ischemic event, and its neuroprotective properties vary according to species, strains and the model of ischemia used. Intrinsic changes in body and brain temperature frequently occur in experimental models of focal and global cerebral ischemia, and may have infl uenced studies on other neuroprotectants. This might be one explanation for the failure of a large amount of translational clinical neuroprotective trials. Hypothermia is the only neuroprotective therapeutic agent for cerebral ischemia that has successfully managed the transfer from bench to bedside, and it is an approved therapy for patients after cardiac arrest and children with hypoxic-ischemic encephalopathy. However, the implementation of hypothermia in the treatment of stroke patients is still far from routine clinical practice. In this article, the authors describe the development of TH in different models of focal and global cerebral ischemia, point out why hypothermia is so efficient in experimental cerebral ischemia, explain why temperature regulation is essential for further neuroprotective studies and discuss why TH for acute ischemic stroke still remains a promising but controversial therapeutic option.
Nagel
Simon
S
Acute Stroke Programme, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, UK. simon.nagel@ndm.ox.ac.uk
Papadakis
Michalis
M
Hoyte
Lisa
L
Buchan
Alastair M
AM
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology* / Q000628:therapy*; D002543:Cerebral Hemorrhage / Q000503:physiopathology* / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D016896:Treatment Outcome