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

Eur Thyroid J. 2025 Feb 3;14(1):e240143. doi: 10.1530/ETJ-24-0143. Print 2025 Feb 1.

Abstract

Objective: 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 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.

Keywords: T3; blood–brain barrier; ischemic stroke; tMCAO; triiodothyronine.

MeSH terms

  • Animals
  • Aquaporin 4 / metabolism
  • Blood-Brain Barrier* / drug effects
  • Blood-Brain Barrier* / pathology
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Stroke* / drug therapy
  • Stroke* / pathology
  • Triiodothyronine* / pharmacology
  • Triiodothyronine* / therapeutic use

Substances

  • Triiodothyronine
  • Neuroprotective Agents
  • Aquaporin 4