Muscle Structure and Function Recovery: Adalimumab-Calcium Channel Synergy in Post-Ischemic Stroke Sarcopenia.

Area of Science:

• Biomedical Science
• Neuroscience
• Muscle Physiology

Background:

• Adalimumab, a TNF-α inhibitor, is clinically used.
• Its role in post-ischemic stroke muscle damage is under investigation.
• Mechanisms involving calcium balance are explored.

Purpose of the Study:

• Investigate adalimumab's effect on muscle structure post-ischemic stroke (IS).
• Elucidate the role of calcium balance in IS-related muscle weakness.
• Validate the synergistic effect of adalimumab and GV-58.

Main Methods:

• Utilized male middle cerebral artery occlusion (MCAO) rat models.
• Employed behavioral, imaging, pathological, and Western blot experiments.
• Explored in vitro mechanisms using L6 and primary muscle cells.

Main Results:

• Ischemic stroke induced sarcopenia (ISS) rats showed decreased motor function and muscle mass.
• Elevated inflammatory factors (IL-1β, IL-6, TNF-α, ROS) and altered muscle protein expression observed.
• Adalimumab treatment significantly improved muscle structure, reduced inflammation, and modulated protein expression.
• RNA-seq implicated the Ca2+ signaling pathway in muscle weakness; adalimumab and GV-58 showed synergistic effects.

Conclusions:

• Adalimumab effectively restores muscle function post-stroke.
• It inhibits inflammation and improves calcium channel dysfunction.
• Combination therapy with GV-58 enhances muscle recovery.