Niclosamide as a Neuroprotective and Anti-Inflammatory Agent: A Potential Therapeutic Approach for Spinal Cord Injury

Spinal cord injury (SCI) is a life-altering condition of the central nervous system resulting in permanent motor, sensory, and functional deficits. The pathophysiology involved includes: primary neuronal necrosis, secondary inflammation, oxidative stress, apoptosis, and impaired neurogenesis, which collectively inhibit tissue repair. Despite efforts, there is currently no effective therapy that offers radial spinal cord regeneration, which highlights our need for pharmacological agents with anti-inflammatory and neuroprotective properties.Niclosamide is an FDA-approved anti-parasitic agent that has received increasing attention recently due to its ability to modulate important signaling pathways such as STAT3, NF-κB, MAPK/ERK, and mTOR. We therefore sought to investigate the therapeutic potential of niclosamide in a rat model of SCI. Animals were given a single intraperitoneal injection of niclosamide (2, 5, or 10 mg/kg) immediately after the clip-induced injury. Functional recovery was assessed by the BBB and Tail-Flick tests for 28 days. The animals that had received 10 mg/kg niclosamide exhibited significant improvement in locomotor and sensory outcomes compared to intact SCI animals.MRI imaging performed on day 7 showed a decrease in lesion size and greater preservation of the surrounding tissue in niclosamide-treated animals. Histopathological assessment on day 28 showed less inflammation and hemorrhage; less vacuolization of the neuron cell bodies; and a decrease in cyst formation. ELISA testing indicated significantly lower levels of IL-6, IL-1β, and TNF-α, and western blot analysis indicated low phosphorylation of ERK1/2, p38 MAPK, STAT3, and mTOR, demonstrating inhibition of inflammatory and apoptotic signaling pathways following injury.These findings collectively indicate that niclosamide has neuroprotective effects across multiple targets and leads to improvements in functional recovery following SCI. These results support niclosamide as a promising candidate for spinal cord repair.