title: Long-term hypothermia reduces infarct volume in aged rats after focal ischemia.
abstract: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. A viable alternative to conventional drug-based neuroprotective therapies is brain/body cooling, or hypothermia. In animal studies of focal ischemia, short-term hypothermia consistently reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 17-month-old male Sprague-Dawley rats. After stroke, the aged rats were exposed for 2 days to a mixture of air and a mild inhibitor of oxidative phosphorylation, hydrogen sulfide (H(2)S), which resulted in sustained, deep hypothermia (30.8+/-0.7 degrees C). Long-term hypothermia led to a 50% reduction in infarct size with a concomitant reduction in the number of phagocytic cells. At the transcription level, hypothermia caused a reduction in the mRNA coding for caspase 12, NF-kappa B and grp78 in the peri-infarcted region, suggesting an overall decrease in the transcriptional activity related to inflammation and apoptosis. Behaviorally, hypothermia was associated with better performance on tests that require complex sensorimotor skills, in the absence of obvious neurological deficits or physiological side effects, in aged rats.
  
  
  CONCLUSIONS
  Prolonged, H(2)S-induced hypothermia is a simple and efficacious method to limit the damage inflicted by stroke in aged rats.
authors.affiliation: Department of Neurology, University of Greifswald, Ellernholzstr. 1-2, 17487 Greifswald, Germany.
authors.forename: Baltromejus
authors.initials: B
authors.lastname: Florian
authors.forename: Raluca
authors.initials: R
authors.lastname: Vintilescu
authors.forename: Adrian Tudor
authors.initials: AT
authors.lastname: Balseanu
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Buga
authors.forename: Olaf
authors.initials: O
authors.lastname: Grisk
authors.forename: Lary C
authors.initials: LC
authors.lastname: Walker
authors.forename: Christof
authors.initials: C
authors.lastname: Kessler
authors.forename: Aurel
authors.initials: A
authors.lastname: Popa-Wagner
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D020520:Brain Infarction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D000091342:Endoplasmic Reticulum Chaperone BiP; D006862:Hydrogen Sulfide / Q000494:pharmacology; D007036:Hypothermia, Induced / Q000379:methods*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009069:Movement Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010086:Oxidative Phosphorylation Coupling Factors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D018836:Inflammation Mediators; D010086:Oxidative Phosphorylation Coupling Factors; D006862:Hydrogen Sulfide