Stroke protection via stimulation of fatty acid oxidation increases astrocyte spare respiratory capacity

Abstract

Stroke is a growing threat among the aging population in the United States, yet few treatments exist for afflicted patients. Research in our lab identified the stimulation of astrocyte mitochondrial metabolism as a protective strategy against stroke. Thyroid hormone has been observed to reduce stroke lesion size, a treatment that we hypothesize is mediated by stimulating fatty acid oxidation (FAO) via the mitochondrial trifunctional protein (MTP). We observe that treatment with the active form of thyroid hormone (T3) protects the mouse brain from stroke in a mechanism requiring astrocyte metabolism and the presence of brain MTP. T3 stimulates an increase in maximal respiration and spare respiratory capacity in a dose‐dependent manner, which is blocked by inhibition of FAO. We also report that T3 increases astrocyte viability and reduces the formation of starvation‐induced lipid droplet formation, suggesting that T3 directly increases astrocyte resistance to conditions of nutrient‐deprivation, such as that observed in stroke. Altogether, our data indicate that thyroid hormone protects the brain against stroke by increasing astrocyte survival in a FAO‐dependent mechanism.Support or Funding InformationResearch supported by National Institutes of Health R01AG007218 and the American Heart Association Predoctoral Fellowship 16PRE27670002