Enhancement of nerve regeneration with nimodipine treatment after sciatic nerve injury.

Peripheral nerve injuries (PNI/s) are common orthopedic conditions, characterized by motor and sensory deficits in the damaged region. There is growing evidence that the L-type calcium channel antagonist nimodipine has neuroprotective and neuroregenerative effects in animal models of neurological disorders. The efficacy of nimodipine on improving motor function and sensation following a sciatic nerve crush model was investigated in male Wistar rats as a model of PNI. At different time periods following damage, we evaluated motor function, sensory recovery, electrophysiology, histomorphometry, and gene expression. Moreover, we used histological and mass ratio analysis of the gastrocnemius muscle to assess atrophy. Our findings suggest that the nimodipine improves motor and sensory function more quickly in the damaged region 2, 4, and 6 weeks after 1 week of treatment. Nimodipine treatment also increased the number of myelinated fibers while decreasing their thickness, as shown by histomorphometry. Additionally, nimodipine treatment increases the mRNA levels of neurotrophic factors (BDNF and NGF), which are known to contribute to the regeneration of injured neurons. The impact of nimodipine in PNI recovery may be due to its stimulation of the CREB signaling pathway and suppression of pro-inflammatory factor production.

Neuroprotective effects of celastrol on sciatic nerve transection model in male Wistar rats.

Objectives: Celastrol is an herbal compound with neuroprotective properties. Our research aimed to assess the neuroprotective properties of celastrol on sciatic nerve transection in rats. Materials and Methods: The rats' left sciatic nerve was cut and sutured directly. The animals were then given 1 or 2 mg/kg celastrol intraperitoneally for two weeks. The sensory and locomotor behaviors of the animals were then evaluated for 16 weeks. Immunohistochemistry, ELISA, and real-time PCR were also utilized to evaluate macrophage polarization, cytokine secretion, and neurotrophin expression in injured nerves. Results: Results showed that both doses of celastrol significantly accelerated nerve regeneration and improved sensorimotor functional recovery when compared with controls. Nevertheless, administration of 2 mg/kg of celastrol significantly outperforms treatment with a dose of 1 mg/kg. Celastrol treatment-induced M2 polarization in macrophages decreased proinflammatory cytokines at the injury site. It also increased the expression of BDNF mRNA. Conclusion: These findings suggest that a two-week treatment with celastrol had neuroprotective effects in a rat sciatic nerve transection model, most likely by inducing macrophage M2 polarization and anti-inflammatory effects.