The use of neuroprotective strategies to mitigate the fatal consequences of ischemic brain
stroke is a focus of robust research activity. We have previously demonstrated that
thyroid hormone (T3; 3,3',5-triiodo-l-
thyronine) possesses neuroprotective and anti-
edema activity in pre-
stroke treatment regimens when administered as a
solution or as a nanoparticle formulation. In this study we have extended our evaluation of
thyroid hormone use in animal models of brain
stroke. We have used both transient
middle cerebral artery occlusion (t-MCAO) and permanent (p-MCAO) models of ischemic brain
stroke. A significant reduction of tissue
infarction and a concurrent decrease in
edema were observed in the t-MCAO model of brain
stroke. However, no benefit of T3 was observed in p-MCAO
stroke setting. Significant improvement of neurological outcomes was observed upon T3 treatment in t-MCAO mice. Further, we tested T2 (3,5-diiodo-l-thyronine) a natural deiodination metabolite of T3 in MCAO model of brain
stroke. T2 potently decreased
infarct size as well as
edema formation. Additionally, we report here that T3 suppresses the expression of aquaporin-4 (AQP4)
water channels which could be a likely mechanism of its anti-
edema activity. Our studies provide evidence to stimulate clinical development of
thyroid hormones for use in ischemic brain
stroke.