Research ReportPost-ischaemic thyroid hormone treatment in a rat model of acute stroke

Stroke is a devastating brain injury that is a leading cause of adult disability with limited treatment options. We examined the effects of prohormone thyroxine (T4) and the underlying mechanisms in the post-ischaemic rat brain after transient focal cerebral ischemia-induced brain injury. Ischaemic injury was induced for 2 h by middle cerebral artery occlusion (MCAo) followed by 24-h reperfusion. T4 (1.1 μg/100 g BW) was administered by intraperitoneally injection twice, at 1 after the onset of ischemia and 6 h after reperfusion. Cerebral infarct area and infarct volume were measured 24 h after MCAo. Furthermore, the mechanism of neuroprotective effect of T4 was investigated with a focus on inflammatory cells, neurotrophins, and transcriptional factors. T4 significantly reduced cerebral infarction, which were accompanied by decreased expression of proapotptic Bax and increased antiapoaptotic Bcl-2 protein. T4 suppressed the activation of astrocytes and microglia, increased the expression of neurotrophic factors (BDNF, GDNF), and altered inflammatory-related prooxidative enzymes (iNOS and COX-2) in ischaemic brain. Moreover, T4 downregulated the phosphorylation of p38 and prevented injury-induced increase of PKCδ. These results revealed that T4 has a promising therapeutic effect in ischaemic stroke treatment protecting the brain from I/R injury, probably by its anti-apoptotic, and anti-inflammatory mechanism.

► T4 protected against brain cerebral ischaemia. ► Gliosis was attenuated by post-ischaemic T4 treatment. ► T4 restored neurotrophins. ► T4 neuroprotection involved p38 MAPK and PKCδ pathways.