Phenserine Mitigates Neuroinflammation, Apoptosis, and Behavioural Deficits to Enhance Motor Function and Recovery in a Mouse Model of Spinal Cord Injury.

Spinal cord injury is a debilitating medical condition that results in paralysis and loss of sensorimotor function below the level of injury. The pathological cascade following the injury involves inflammation, apoptosis, blood-spinal cord barrier integrity disruption, axonal damage, glial scarring, and demyelination. This study evaluates the therapeutic potential of phenserine, a lipophilic phenyl carbamate derivative with neuroprotective, anti-inflammatory, and anti-apoptotic properties, in a compression-induced spinal cord injury model in C57bl/6 mice. Intraperitoneal administration of phenserine (5 mg/kg, twice daily for 5 days) significantly reduced inflammatory responses and blood-spinal cord barrier permeability at 1 day post-injury. By 7 days, it attenuated apoptotic signalling, and by 28 days, it reduced glial scarring and enhanced markers of axonal integrity and myelination. Neurobehavioral assessments further indicated that phenserine treatment improved motor and functional recovery outcomes. Collectively, our findings highlight phenserine as a promising therapeutic candidate that targets multiple secondary injury mechanisms to promote neuroprotection and functional restoration following spinal cord injury, marking a novel approach in managing traumatic spinal cord injury.