Dl‐3‐n‐butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF‐κB signalling

In this study, we examined the neuroprotective effects and anti‐inflammatory properties of Dl‐3‐n‐butylphthalide (NBP) in Sprague‐Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL‐positive cells at 7 days post‐injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF‐κB expression at 1 day post‐injury. In a co‐culture system with BV‐2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV‐2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV‐2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF‐κB expression in BV‐2 cells. Our findings demonstrate that NBP may have neuroprotective and anti‐inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF‐κB signalling.     

Cellular reactions and compensatory tissue re‐organization during spontaneous recovery after spinal cord injury in neonatal mice

Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re‐establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al.: PLoS One 8 (2013)). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals. Early during the period of recovery, regressive events dominated. Tissue loss near the injury was severe, with about 80% loss of neurons and a similar loss of axons that later make up the white matter. There was no sign of neurogenesis, no substantial astroglial or microglial proliferation, no change in the ratio of M1 and M2 microglia and no appreciable generation of the terminal complement peptide C5a. One day after injury the number of synaptic terminals on lumbar motoneurons had dropped by a factor of 2, but normalized by 6 days. The ratio of VGLUT1/2+ to VGAT+ terminals remained similar in injured and uninjured spinal cords during this period. By 24 days after injury, when functional recovery is nearly complete, the density of 5‐HT+ fibers below the injury site had increased by a factor of 2.5. Altogether this study shows that cellular reactions are diverse and dynamic. Pronounced recovery of both excitatory and inhibitory terminals and an increase in serotonergic innervation below the injury, coupled with a general lack of inflammation and reactive gliosis, are likely to contribute to the recovery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 928–946, 2017     

Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling

Dexmedetomidine (Dex) has been proven to exert protective effects on multiple organs in response to ischaemia‐reperfusion injury, but the specific mechanism by which this occurs has not been fully elucidated. The purpose of this study was to investigate whether Dex attenuates spinal cord ischaemia‐reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS). Our team established a model of SCIRI and utilized the endoplasmic reticulum agonist thapsigargin. Dex (25 g/kg) was intraperitoneally injected 30 minutes before spinal cord ischaemia. After 45 minutes of ischaemia, the spinal cord was reperfused for 24 hours. To evaluate the neuroprotective effect of Dex on SCIRI, neurological function scores were assessed in rats and apoptosis of spinal cord cells was determined by TUNEL staining. To determine whether the endoplasmic reticulum apoptosis pathway CNPY2‐PERK was involved in the neuroprotective mechanism of Dex, the expression levels of related proteins (CNPY2, GRP78, PERK, CHOP, caspase‐12, caspase‐9 and caspase‐3) were detected by western blot analysis and RT‐PCR. We observed that Dex significantly increased the neurological function scores after SCIRI and decreased apoptosis of spinal cord cells. The expression of ERS‐related apoptosis proteins was significantly increased by SCIRI but was significantly decreased in response to Dex administration. Taken together, the results of this study indicate that Dex may attenuate SCIRI by inhibiting the CNPY2‐ERS apoptotic pathway.     

Baicalin effects on rats with spinal cord injury by anti‐inflammatory and regulating the serum metabolic disorder

Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by the enzyme‐linked immunosorbent assay method. Expressions of inflammation‐related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low‐dose and high‐dose groups. The levels of TNF‐α, IL‐1β, and IL‐6 in the SCI group were significantly increased. The expressions of NF‐κB p65, NF‐κB p50, p‐IκBα, and IKKα in the SCI group showed the opposite trend compared with the low‐dose and high‐dose groups. Compared with the sham group, glutamine, levels of 3‐OH‐butyrate, N‐acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti‐inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats.