Hypothyroidism Alleviates Cerebral Infarction but Exacerbates Blood-brain Barrier Disruption Following Transient Ischemic Stroke in Rats

Abstract Hypothyroidism is both a risk factor for stroke by disrupting fat metabolism and increasing atherosclerosis also a potential protective factor against its injuries. Hypothyroidism can influence the function of cerebral vessels such that BBB disruption is a reported complication of untreated hypothyroidism. The effects of hypothyroidism on cerebral vascular function in normal condition and following the ischemia-reperfusion is investigated in this study. Two groups of control euthyroid (CN) and hypothyroid (HPO) rats were studied. Hypothyroidism was induced by feeding methazole dissolved in drinking water (0.025 g/100 ml) for 4 weeks. After ensuring the hypothyroidism induction, cerebral ischemia-reperfusion was induced by MCAO. Following the reperfusion period, neuromotor dysfunction were evaluated and after removal of the brain, the volume of the infarct area was studied by the TTC staining and the BBB destruction was evaluated by the Evans Blue (EB) extravasation technique. Treatment with methimazole significantly reduced the levels of thyroid hormones (T3:198±4 vs.73±3µg/dl and T4: 3.08±0.07 vs.1.03±0.04µg/dl) in HPO. Furthermore, many clinical signs of hypothyroidism were developed in this group of animals. Hypothyroidism was associated with increased cerebral vascular permeability under non-ischemic conditions and exacerbation of BBB destruction after ischemia. However, neuromotor disorders and infarct volume were lower in hypothyroid animals than in euthyroid animals. Hypothyroidism has dual effects on ischemia-induced cerebrovascular damages. Aggravation of BBB destruction and alleviation of neuronal death following the cerebral ischemia-reperfusion are two converse effects of hypothyroidism. To clarify the exact mechanisms by which hypothyroidism causes these effects more investigations is required.