ABSTRACT NUMBER: ESOC2026A1926 EFFECTS OF ACUTE THYROID RECEPTOR MODULATION IN EXPERIMENTAL ISCHEMIC STROKE

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 (p>0.1). 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 (p<0.05); DBD conferred no effects (p>0.1). TRβ agonism with Sobetirome did not show any clinical effect or penumbral neuronal benefit (p>0.1). 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