Selective brain hypothermia attenuates focal cerebral ischemic injury and improves long-term neurological outcome in aged female mice

Abstract

Aims: This study aimed to investigate the effects of mild selective brain hypothermia on aged female ischemic mice. Methods: A distal middle cerebral artery occlusion (dMCAO) model was established in aged female mice, who were then subjected to mild selective brain hypothermia immediately after the dMCAO procedure. Neurological behavioral examinations were conducted prior to and up to 35 days post-ischemia. Infarct volume, brain atrophy, pro-inflammation, and anti-inflammation microglia/macrophages phenotype and white matter injury were evaluated by immunofluorescence staining. Correlations between neurological behaviors and histological parameters were evaluated by Pearson product linear regression analysis. Results: Sensorimotor and cognitive function tests confirmed the protective effect of mild selective brain hypothermia in elderly female ischemic mice. In addition, hypothermia decreased the infarct volume and brain atrophy induced by focal cerebral ischemia. Furthermore, hypothermia alleviated ischemia-induced short-term and long-term white matter injury, which was correlated with behavioral deficits. Finally, hypothermia suppressed the harmful immunological response by promoting the transformation of pro-inflammatory microglia/macrophages to anti-inflammatory phenotype. This polarization was negatively correlated with neuronal loss and white matter injury. Conclusion: Mild selective brain hypothermia promoted long-term functional recovery by alleviating white matter damage in an aged female mouse model of ischemia.