ABSTRACT
Nerve scarring after peripheral nerve injury can severely hamper nerve regeneration and functional recovery. Further, the anti-inflammatory cytokine, interleukin-10, can inhibit nerve scar formation. Saikosaponin a (SSa) is a monomer molecule extracted from the Chinese medicine, Bupleurum. SSa can exert anti-inflammatory effects in spinal cord injury and traumatic brain injury. However, it has not been shown whether SSa can play a role in peripheral nerve injury. In this study, rats were randomly assigned to three groups. In the sham group, the left sciatic nerve was directly sutured after exposure. In the sciatic nerve injury (SNI) + SSa and SNI groups, the left sciatic nerve was sutured and continuously injected daily with SSa (10 mg/kg) or an equivalent volume of saline for 7 days. Enzyme linked immunosorbent assay results demonstrated that at 7 days after injury, interleukin-10 level was considerably higher in the SNI + SSa group than in the SNI group. Masson staining and western blot assay demonstrated that at 8 weeks after injury, type I and III collagen content was lower and nerve scar formation was visibly less in the SNI + SSa group compared with the SNI group. Simultaneously, sciatic functional index and nerve conduction velocity were improved in the SNI + SSa group compared with the SNI group. These results confirm that SSa can increase the expression of the anti-inflammatory factor, interleukin-10, and reduce nerve scar formation to promote functional recovery of injured sciatic nerve.
ABSTRACT
The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 µg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.
