Abstract Background and aims Data on the role of thyroid hormone (TH) signaling in stroke have been contradictory between studies. Here, we aim to study the acute effects after TH-agonist/-antagonist treatment in experimental stroke. Methods C57BL/6 mice (n=90) underwent transient focal middle cerebral artery occlusion (fMCAO) for 1 hour, followed clinically up to day 3. Animals were randomized blindly to groups receiving either T3 (at doses of 25 μg/kg or 200 μg/kg), Desethyl-amiodarone (DEA) or Desbutyl-dronedarone (DBD) (at doses 25mg/kg) at reperfusion and on day 1; Sobetirome at 1mg/kg at reperfusion and daily up to day 3; controls received the corresponding vehicle. Histopathological brain studies on cryosections included infarct and hemispheric edema volumetry, as well as astrocytosis and neuronal death using a novel developed FluoroJadeB method for histological detection of penumbra from core and healthy tissue. Results Acute high-dose of T3 did not improve brain edema, infarct volume or neuronal survival compared to controls (p0.1). Low-dose T3 worsened penumbral neuronal survival (p=0.0086). TH-receptors’ antagonism with DEA induced a clinical worsening with corresponding increased infarct size and neuronal death at day 3 (p0.05); DBD conferred no effects (p0.1). TRβ agonism with Sobetirome did not show any clinical effect or penumbral neuronal benefit (p0.1). Conclusions Acute post-ischemic TH-receptor activation with low- and high- T3 doses or sobetirome confers mixed effects that need further clarification. However, TH-receptors antagonism with DEA (the active metabolite of amiodaron) is detrimental for stroke and should probably be avoided, at least during the first 3 days post-ischemia. Conflict of interest APav and NZ were supported by Tsetis Foundation, CP, IM and AL were supported by Uni-pharma S.A. with Research Grants. AK: nothing to disclose, IT: nothing to disclose, VA: nothing to disclose, EK: nothing to disclose, APap: nothing to disclose, MG: nothing to disclose, APap: nothing to disclose
Pavlopoulos et al. (2026) studied this question.