Telmisartan Ameliorates Blood-Brain Barrier Disruption in a High-Salt Diet Mouse Model

Area of Science:

• Neuroscience
• Cardiovascular Research
• Pharmacology

Background:

• Hypertension-induced blood-brain barrier (BBB) disruption increases neurological complication risk.
• Telmisartan, an angiotensin II receptor antagonist, treats hypertension but its effect on BBB disruption in high-salt diet (HSD) models is understudied.

Purpose of the Study:

• To investigate Telmisartan's effects on HSD-induced BBB disruption in mice.
• To elucidate the molecular mechanisms underlying Telmisartan's action on BBB integrity.

Main Methods:

• Induced hypertension in mice using a high-salt diet (HSD).
• Administered Telmisartan and assessed BBB permeability (Evans blue extravasation).
• Analyzed expression of intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (E-selectin), and Claudin-1.
• Conducted in vitro studies using human brain microvascular endothelial cells (HBMECs) and assessed trans-endothelial electrical resistance (TEER).
• Investigated the role of the Wnt/β-catenin signaling pathway.

Main Results:

• Telmisartan mitigated brain vascular inflammation and reduced BBB permeability in HSD mice.
• Downregulated ICAM-1 and E-selectin mRNA and protein expression.
• Restored Claudin-1 expression and inhibited Evans blue dye extravasation.
• In vitro, Telmisartan reduced Angiotensin II-induced permeability, increased TEER, and restored Claudin-1.
• Activated the Wnt/β-catenin signaling pathway, which was essential for Telmisartan's protective effects.

Conclusions:

• Telmisartan effectively manages HSD-induced hypertension and preserves BBB integrity.
• Neuroprotection is achieved by reducing endothelial inflammation and restoring tight junction proteins via the Wnt/β-catenin pathway.
• Telmisartan shows potential as a therapeutic agent against neurological complications associated with HSD-induced BBB disruption.