Original Article
Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1919–1930; doi:10.1038/sj.jcbfm.9600492; published online 11 April 2007
Transient cooling during early reperfusion attenuates delayed edema and infarct progression in the Spontaneously Hypertensive Rat. Distribution and time course of regional brain temperature change in a model of postischemic hypothermic protection
This work was supported by the Neurology Support Fund and Semmes-Murphey Chair of Excellence, University of Tennessee Health Science Center (WAP) and USPHS grants NS32344 and NS42267 (TSN).
Toshiaki Kurasako1,2, Liang Zhao1, William A Pulsinelli1 and Thaddeus S Nowak Jr1
1Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Correspondence: Dr TS Nowak, Jr, Department of Neurology, University of Tennessee, 855 Monroe Ave., Link 415, Memphis, Tennessee 38163, USA. E-mail: tnowak@utmem.edu
2Current address: Dr Kurasako, Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2-5-1-Shikata-cho, Okayama City, Okayama 700-8558, Japan.
Received 2 November 2006; Revised 12 February 2007; Accepted 1 March 2007; Published online 11 April 2007.
Abstract
The temperature threshold for protection by brief postischemic cooling was evaluated in a model of transient focal ischemia in the Spontaneously Hypertensive Rat, using an array of epidural probes to monitor regional brain temperatures. Rats were subjected to 90 mins tandem occlusion of the right middle cerebral artery (MCA) and common carotid artery. Systemic cooling to 32°C was initiated 5 mins before recirculation, with simultaneous brain cooling to temperatures ranging from 28°C to 32°C within the MCA territory by means of a temperature-controlled saline drip. Rewarming was initiated at 2 h recirculation and was complete within 30 mins. Tissue damage and edema volume showed clear temperature-dependent reductions when evaluated at 3 days survival, with no protection evident in the group at 32°C but progressive effects on both parameters after deeper cooling. A particularly striking effect was the essentially complete elimination of edema progression between 1 and 3 days. Temperature at distal sites within the MCA territory better predicted reductions in lesion volume, indicating that protection required effective cooling of the penumbral regions destined to be spared. These results show that even brief cooling can be highly protective when initiated at the time of recirculation after focal ischemia, but indicate a substantially lower temperature threshold for hypothermic protection than has been reported for other strains, occlusion methods, and cooling durations.
Keywords:
brain cooling, edema, focal ischemia, hypothermic protection, reperfusion injury
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