Triiodothyronine treatment in mice improves stroke outcome and reduces blood-brain barrier damage.

Objective Thyroid hormones (TH) control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3',5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. Methods Stroke was induced in mice by transient middle cerebral artery occlusion (tMCAO) and T3 was administered at different doses and time points before and after stroke. Results We demonstrated a dose-dependent protective effect of T3 reducing infarct volumes with an optimal T3 dosage of 25 µg/kg. In addition, we observed a time-dependent effectiveness that was most profound when T3 was administered 1 h after tMCAO (P < 0.001), with a gradual reduction in efficacy at 4.5 h (P = 0.066), and no reduction in infarct volumes when T3 was injected with an 8 h delay (P > 0.999). The protective effect of acute T3 treatment persisted for 72 h post-tMCAO (P < 0.01) and accelerated the recovery of motor function by day 3 (P < 0.05). In-depth investigations further revealed reduced cerebral edema and diminished blood-brain barrier leakage, indicated by reduced extravasation of Evans Blue and diminished aquaporin-4 expression. Conclusion Our findings suggest that T3 may be a promising intervention for ischemic stroke in the acute phase.