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Osteopontin (OPN) is a multifunctional matrix glycoprotein with neuroprotective and immunomodulatory properties. This study explored the potential of OPN-loaded acellular nerve allografts (ANAs) to repair sciatic nerves in male Wistar rats. The research also delved into the impact of OPN on macrophage phenotypes. We reconstructed a 10 mm nerve gap with ANAs containing OPN at 2 nM and 4 nM. The sciatic functional index (SFI) and paw withdrawal reflex latency (WRL) showed the significant efficacy of ANA/OPN (2 nM) in enhancement of target organ reinnervation and subsequent sensorimotor recovery compared to other groups. Electrophysiological and histomorphometric analyses further supported the regenerative properties of ANA/OPN (2 nM). Additionally, ANA/OPN (2 nM) promoted macrophage polarization towards an M2 phenotype and reduced proinflammatory cytokines at the injury site. In conclusion, the study suggested that ANA loaded with 2 nM OPN effectively repaired transected sciatic nerves in rats, potentially through enhancing axonal sprouting and exerting anti-inflammatory effects.

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BACKGROUND: Epothilone B (EpoB) is a microtubule-stabilizing agent with neuroprotective properties. OBJECTIVES: This study examines the regenerative properties of ANA supplemented with EpoB on a sciatic nerve deficit in male Wistar rats. METHODS: For this purpose, the 10 mm nerve gap was filled with acellular nerve allografts (ANAs) containing EpoB at 0.1, 1, and 10 nM concentrations. The sensorimotor recovery was evaluated up to 16 weeks after the operation. Real-time PCR, histomorphometry analysis, and electrophysiological evaluation were also used to evaluate the process of nerve regeneration. RESULTS: ANA/EpoB (0.1 nM) significantly improved sensorimotor recovery in rats compared to ANA, ANA/EpoB (1 nM), and ANA/EpoB (10 nM) groups. This led to reduced muscle atrophy, improved sciatic functional index, and thermal paw withdrawal reflex latency, indicating nerve regeneration and target organ reinnervation. The electrophysiological and histomorphometry findings also confirmed the ANA/EpoB regenerative properties (0.1 nM). EpoB only enhanced ANA regenerative properties at 0.1 nM, with no therapeutic effects at higher concentrations. CONCLUSION: Totally, we concluded that ANA loaded with 0.1 nM EpoB can effectively reconstruct the transected sciatic nerve in rats, likely by enhancing axonal sprouting and extension.

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Despite the innate regenerative capacity of peripheral nerves, regeneration after a severe injury is insufficient, and sensorimotor recovery is incomplete. As a result, finding alternative methods for improving regeneration and sensorimotor recovery is essential. In this regard, we investigated the effect of IL-33 treatment as a chemokine with neuroprotective properties. IL-33 can facilitate tissue healing by potentiating the type 2 immune response and polarizing macrophages toward the pro-healing M2 phenotype. However, its effects on nerve regeneration remain unclear. Therefore, this research aimed to evaluate the neuroprotective effects of IL-33 on sciatic nerve injury in male C57BL/6 mice. After crushing the left sciatic nerve, the animals were given 10, 25, or 50 µg/kg IL-33 intraperitoneally for seven days. The sensorimotor recovery was then assessed eight weeks after surgery. In addition, immunohistochemistry, ELISA, and real-time PCR were used to assess macrophage polarization, cytokine secretion, and neurotrophic factor expression in the injured nerves. IL-33 at 50 and 25 µg/kg doses could significantly accelerate nerve regeneration and improve sensorimotor recovery when compared to 10 µg/kg IL-33 and control groups. Furthermore, at 50 and 25 µg/kg doses, IL-33 polarized macrophages toward an M2 phenotype and reduced proinflammatory cytokines at the injury site. It also increased the mRNA expression of NGF, VEGF, and BDNF. These findings suggest that a seven-day IL-33 treatment had neuroprotective effects in a mouse sciatic nerve crush model, most likely by inducing macrophage polarization toward M2 and regulating inflammatory microenvironments.

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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.

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Following severe peripheral nerve injury (PNI), regeneration is often insufficient and functional recovery is incomplete. Any agents that limit the spread of neural tissue damage may enhance the nerve regeneration. In this regard, statins have been shown to have neuroprotective properties. We investigated the effects of Lovastatin against sciatic nerve crush injury in male Wistar Rats. Lovastatin or vehicle was given parenteraly to rats for 7 days postoperative. In Lovastatin treatment groups, a single dose of agent (2 and 5mg/kg) was administered daily. The control group was given vehicle in the same manner. The rats were subjected to crush injury in the left sciatic nerve with non-serrated clamp for 30s. Behavioral, electrophysiological and morphological alterations were evaluated during the experimental period. Results showed that Lovastatin in a dose of 5mg/kg could significantly (P < 0.05) accelerate regeneration process and functional recovery. Also results demonstrated that morphometric parameters such as mean axonal number and myelin thickness were significantly higher in Lovastatin (5mg/kg) treatment groups compared to controls (P < 0.05). These findings suggest that a short-term course treatment with Lovastatin can protect against sciatic nerve injury. Findings indicate that postoperative administration of Lovastatin led to accelerate regeneration process and motor function recovery in nerve crush model in rats. This effect might be due to the anti-inflammatory, immunomodulatory or anti-oxidative properties of Lovastatin. It is clear that more research is needed to confirm these findings.

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Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (P<0.05). Citicoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (P<0.05). Additionally, citicoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (P<0.05). The pentobarbital induced sleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect.

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