Will anyone in stroke actually think of and do human testing of this for stroke? Of course not, there aren't two functioning neurons anywhere in stroke!
Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!
OH NO! your doctor KNOWS NOTHING AND DOES NOTHING!
Clemizole Mitigates Traumatic Brain Injury by Inhibiting Oxidative Stress, Neuroinflammation, and Apoptosis
Abstract
Traumatic brain injury (TBI) triggers complex secondary pathological mechanisms, including neuroinflammation, oxidative stress, and apoptosis, contributing to long-term cognitive and motor deficits. This study investigates the neuroprotective potential of Clemizole, a known TRPC5 inhibitor, in a weight-drop rat model of TBI. Target prediction analyses using Swiss Target Prediction and CTD databases identified 159 overlapping genes between Clemizole and TBI. Protein–protein interaction network and hub gene analyses highlighted key proteins, such as TNF-α, CASP3, MMP-9, and TRPC5, implicating them in TBI pathogenesis. KEGG pathway enrichment revealed Clemizole-targeted pathways, including PI3K-Akt, TNF signaling, and apoptosis. After TBI, behavioral assessments showed that Clemizole significantly improved neurological scores, grip strength, locomotor activity, and spatial learning deficits. Biochemical assays revealed that Clemizole dose-dependently reduced nitrite and MDA levels while restoring GSH, indicating attenuation of oxidative stress. H&E (hematoxylin and eosin) and cresyl violet staining confirmed reduced neuronal degeneration and preserved cortical integrity. Clemizole also downregulated inflammatory cytokines and glial markers (Iba-1 and GFAP), alongside restoring BBB integrity via upregulation of tight junction proteins and suppressing MMP-9 expression. Furthermore, Clemizole activated the PI3K-Akt signaling pathway, decreasing the expression of pro-apoptotic proteins (Bax, caspase-9 and caspase-3) and restoring Bcl-2 levels. Importantly, Clemizole decreased TRPC5 expression and attenuated CHOP-mediated ER stress, suggesting a mechanistic link between TRPC5 inhibition and PI3K-Akt-mediated neuroprotection. Collectively, these findings demonstrate that Clemizole confers multifaceted neuroprotection following TBI by targeting TRPC5-mediated calcium dysregulation, restoring PI3K-Akt signaling, and attenuating oxidative, inflammatory, and apoptotic cascades. This study identifies Clemizole as a promising therapeutic candidate for mitigating secondary brain injury and promoting functional recovery after TBI.
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