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Post-ischemic triiodothyronine treatment improves stroke outcome by stabilizing the blood-brain barrier

Ullrich, D.; Fuehrer-Sakel, D.; Heuer, H.; Mayerl, S.; Haupeltshofer, S.; Schmitt, L.-I.; Leo, M.; Hagenacker, T.; Kleinschnitz, C.; Langhauser, F.

2023-11-21 neuroscience
10.1101/2023.11.21.568025 bioRxiv
Show abstract

Thyroid hormones 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 triiodothyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. To this end we investigated the consequences of T3 treatment in an experimental model of ischemic stroke in mice. Our research demonstrated a dose-dependent protective effect of T3 by reducing infarct volumes, with the optimal T3 dosage identified as 25 {micro}g/kg. In addition, we observed a time-dependent effectiveness that was most pronounced when T3 was administered 1 h after transient middle cerebral artery occlusion, with a gradual reduction in efficacy at 4.5 h, and no reduction in infarct volumes when T3 was injected with an 8 h delay. This protective effect persisted for 72 h post-tMCAO, and had accelerated the recovery of motor function by day 3. In-depth investigations further revealed stabilization of the blood-brain barrier, indicated by reduced extravasation of Evans Blue and diminished aquaporin-4 expression, with reduced inflammation and less cell death as underlying reasons. Our findings suggest that thyroid hormones may be a promising intervention for clinical stroke.

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