Clemizole Mitigates Traumatic Brain Injury by Inhibiting Oxidative Stress, Neuroinflammation, and Apoptosis

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Traumatic brain injury (TBI) induces neuroinflammation, oxidative stress, and apoptosis, leading to cognitive and motor deficits.
• Secondary injury mechanisms exacerbate TBI pathology and long-term outcomes.

Purpose of the Study:

• To investigate the neuroprotective potential of Clemizole, a TRPC5 inhibitor, in a rat model of TBI.
• To elucidate the molecular mechanisms underlying Clemizole's therapeutic effects in TBI.

Main Methods:

• A weight-drop rat model of TBI was used.
• Target prediction, gene interaction network, and pathway enrichment analyses were performed.
• Behavioral tests, biochemical assays, histological staining, and Western blotting were employed.

Main Results:

• Clemizole improved neurological scores, grip strength, locomotor activity, and spatial learning in TBI rats.
• It reduced oxidative stress markers (nitrite, MDA), attenuated inflammation (cytokines, glial markers), and decreased apoptosis (Bax, caspases).
• Clemizole activated the PI3K-Akt pathway, restored BBB integrity, reduced TRPC5 expression, and alleviated ER stress.

Conclusions:

• Clemizole demonstrates multifaceted neuroprotection against TBI by inhibiting TRPC5, modulating PI3K-Akt signaling, and mitigating secondary injury cascades.
• Clemizole is a promising therapeutic candidate for TBI, promoting functional recovery.