Reassessment of Neuroprotective Efficacy of TUDCA in Ischemic Stroke: A Multi-Model In Vivo and In Vitro Study.

Intravenous TUDCA (100 mg/kg) did not significantly reduce infarct volume in mice subjected to transient middle cerebral artery occlusion (tMCAO) regardless of administration timing.

• Male C57BL/6 mice were used in the tMCAO model
• TUDCA was administered intravenously at 100 mg/kg either one hour before or after stroke induction
• Infarct size was a primary outcome measure
• No statistically significant reduction in infarct volume was observed in either pre- or post-treatment groups

Intravenous TUDCA (100 mg/kg) did not significantly reduce infarct volume in mice subjected to permanent distal middle cerebral artery occlusion (dMCAO).

• Male C57BL/6 mice were used in the dMCAO model
• TUDCA was administered intravenously at 100 mg/kg either one hour before or after stroke induction
• Infarct size was assessed as a primary outcome measure
• No significant neuroprotective effect was observed in either pre- or post-treatment conditions

TUDCA did not improve neurological outcomes in either the tMCAO or dMCAO mouse models of ischemic stroke.

• Neurological score was used as a primary outcome measure alongside infarct size
• Treatment was administered either one hour before or after stroke induction in both models
• No significant improvement in neurological score was detected under any tested condition
• Both pre- and post-treatment paradigms were assessed

TUDCA did not attenuate blood-brain barrier (BBB) leakage as assessed by IgG extravasation in vivo.

• IgG extravasation served as a primary outcome measure of BBB integrity in vivo
• Measurements were taken in both the tMCAO and dMCAO mouse models
• TUDCA administration at 100 mg/kg either pre- or post-stroke did not significantly reduce IgG extravasation
• BBB leakage was assessed across both ischemic stroke models and both timing conditions

TUDCA did not preserve barrier permeability or ZO-1 expression in a human iPSC-derived BBB organ-on-chip system under normoxic or hypoxic conditions.

• A human iPSC-derived BBB organ-on-chip system was used to further assess BBB integrity in vitro
• Experiments were conducted under both normoxic and hypoxic conditions to model ischemia
• ZO-1, a tight junction protein, was evaluated as a marker of BBB integrity
• Neither barrier permeability nor ZO-1 expression was preserved by TUDCA treatment in either condition

The study employed a multi-model approach including two distinct in vivo mouse models of ischemic stroke and one in vitro human iPSC-derived BBB organ-on-chip system.

• In vivo models included transient middle cerebral artery occlusion (tMCAO) and permanent distal middle cerebral artery occlusion (dMCAO)
• The in vitro model used a human iPSC-derived BBB organ-on-chip system
• Male C57BL/6 mice were used for all in vivo experiments
• Primary outcome measures included infarct size, neurological score, IgG extravasation, barrier permeability, and ZO-1 expression

The authors conclude that further optimization of dosing and administration strategies is required to fully evaluate TUDCA's therapeutic potential in ischemic stroke.

• The dose tested was 100 mg/kg administered intravenously
• Administration timing tested was one hour before or after stroke induction
• The authors acknowledge that conditions tested did not demonstrate an effect of TUDCA on ischemic brain injury or BBB integrity features
• The conclusion does not rule out therapeutic potential but identifies current conditions as insufficient to demonstrate efficacy

TUDCA was evaluated as a candidate neuroprotective agent in the context of the gut-brain axis and microbial metabolites as modulators of stroke outcome.

• TUDCA is described as a taurine-conjugated secondary bile acid
• Ischemic stroke accounts for 87% of all strokes and remains a leading cause of mortality and morbidity worldwide
• Emerging evidence on the gut-brain axis and microbial metabolites positioned TUDCA as a candidate therapeutic
• The study represents a reassessment of TUDCA's neuroprotective efficacy specifically in ischemic stroke