ObjectiveTo investigate the effect of saikosaponin a (SSa) on the levels of immune inflammation in rats with acute spinal cord injury and its possible mechanism.MethodsSeventy-two Sprague Dawley rats (weighing, 220-250 g) were randomly divided into sham operation group (group A), spinal cord injury group (group B), and SSa treatment group (group C) respectively, 24 rats in each group. The spinal cord injury model was induced by using the Allen’s method in groups B and C; the spinous process and vertebral plate at both sides were cut off by lamina excision to expose the spinal cord in group A. The rats were given intraperitoneal injection of 10 mg/kg SSa in group C and equal volume of normal saline in group B at immediate after injury. The spinal cord tissue was harvested from 18 rats of each group at 24 hours after operation to measure the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) by ELISA, to detect the expressions of nuclear factor κB (NF-κB) P65, NF-κB P-P65, and aquaporin 4 (AQP4) by Western blot and to observe the morphology of spinal cord by HE staining. The motor function of the lower limbs was evaluated by BBB score and tiltboard experiment in 6 rats at 1, 3, 7, 14, 21, and 28 days after injury.ResultsThe BBB score and tiltboard experiment maximum angle were significantly higher in group A than groups B and C at each time point (P<0.05) and in group C than group B at 14, 21, and 28 days after operation (P<0.05). ELISA test showed that the concentrations of TNF-α and IL-6 were significantly lower in group A than groups B and C, and in group C than group B (P<0.05). Western blot results showed that the protein expression levels of NF-κB P65, NF-κB P-P65, and AQP4 were significantly lower in group A than groups B and C, and in group C than group B (P<0.05). HE staining demonstrated normal neurons of the spinal cord and no obvious lesion in group A; neuronal cells were observed in the injured area of group B, with hemorrhage, neutrophil infiltration, and nerve cell edema in the injured area; the neuronal cells were visible in the spinal cord of group C, with microglia mild hyperplasia, and the pathological changes were improved when compared with group B.ConclusionSSa has neuroprotective effects on acute spinal cord injury in rats by inhibiting NF-κB signaling pathway and AQP4 protein expression and reducing inflammation response and edema.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system that primarily affects the optic nerves and spinal cord. Most patients have positive serum antibody of aquaporin-4 (AQP4), which targets the AQP4 protein expressed on the end-feet of astrocytes. Although the prevalence of NMOSD is limited to around (1-2)/100 000, the recurrence rate is high. Repeated and severe immune-mediated attacks can quickly lead to blindness and paralysis if undiagnosed and untreated. While high-dose methylprednisolone and plasma exchange are used in the acute phase, the treatment for recurrent prevention is limited. In recent years, researchers developed several kinds of monoclonal antibodies targeting different nodes of immune pathogenic process, including satralizumab (an interleukin-6 receptor inhibitor), inebilizumab (an antibody against CD19+ B cells), and eculizumab (an antibody blocking the C5 component of complement). In several randomized controlled clinical trials, these monoclonal antibodies decreased the relapse rate significantly in NMOSD. These emerging treatments have greatly changed the treatment of NMOSD.