Elsevier

Neuroscience Letters

Volume 438, Issue 2, 20 June 2008, Pages 180-185
Neuroscience Letters

Long-term hypothermia reduces infarct volume in aged rats after focal ischemia

https://doi.org/10.1016/j.neulet.2008.04.020Get rights and content

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 (H2S), which resulted in sustained, deep hypothermia (30.8 ± 0.7 °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, H2S-induced hypothermia is a simple and efficacious method to limit the damage inflicted by stroke in aged rats.

References (27)

  • U. Dirnagl

    Bench to bedside: the quest for quality in experimental stroke research

    J. Cereb. Blood Flow Metab.

    (2006)
  • J.W. Elrod et al.

    Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function

    Proc. Natl. Acad. Sci. U.S.A.

    (2007)
  • S.R. Hotchkiss et al.

    Apoptosis and caspases regulate death and inflammation in sepsis

    Nat. Rev. Immunol.

    (2006)
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      The effect of exogenous H2S in I/R injury in various organs has been studied a lot [20,21]. In the brain, previous study found that a 2-day post-stroke exposure to a mixture of air and H2S gas resulted in reduced infarct size and better behavioral performances in aged rats [22]. Some other studies used H2S donor (such as diallyl sulfide, ADT and NaHS) to provide external H2S to facilitate the convenience of drug administration.

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