lignans and Spinal-Cord-Injuries

To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism.. Animal experiment study.. Institute of Neuroscience of Chongqing Medical University.. Total of 69 Sprague-Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline.. In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C.. Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

Topics: Animals; Apoptosis; Biphenyl Compounds; Caspase 12; Caspase 3; Cytochromes c; Demyelinating Diseases; Endoplasmic Reticulum; Humans; Lignans; Mitochondria; Myelin Sheath; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries

Schisandrin B is an active monomer of the Chinese magnolia vine (Schisandra chinensis) that can reduce transaminase activity in liver cells, inhibit lipid peroxidation, enhance antioxidant status, has protective effects in the liver and has antitumor effects. The present study investigated the potential protective effects of schisandrin B on the p53 signaling pathway in attenuating the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury (TSCI) in adult rats. Behavioral examination, inclined plate test and spinal cord water content were used to evaluate the protective effect of schisandrin B in TSCI rats. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor (NF)‑κB subunit p65 and tumor necrosis factor (TNF)‑α were examined using ELISA kits. Western blot analysis was performed to analyze the protein expression of caspase‑3 and phosphorylated (p)‑p53 in TSCI rats. In the present study, schisandrin B improved behavioral examination results and the maximum angle of inclined plate test, and inhibited spinal cord water content in rats with TSCI. Notably, schisandrin B reduced the activation of traumatic injury‑associated pathways, including SOD, MDA, NF‑κB p65 and TNF‑α, in TSCI rats. In addition, schisandrin B suppressed the TSCI‑induced expression of caspase‑3 and p‑p53 in TSCI rats. These results indicated that schisandrin B may attenuate the inflammatory response, oxidative stress and apoptosis in TSCI rats by inhibiting the p53 signaling pathway in adult rats.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Biomarkers; Caspase 3; Cyclooctanes; Disease Models, Animal; Lignans; Male; NF-kappa B; Oxidative Stress; Polycyclic Compounds; Rats; Signal Transduction; Spinal Cord Injuries; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53

Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity but delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans. We have, therefore, identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration and neurite outgrowth in an L1-dependent manner. Here, we assessed the functions of two L1 mimetics, trimebutine and honokiol, in regeneration following SCI in young adult mice. Using the Basso Mouse Scale (BMS) score, we found that ground locomotion in trimebutine-treated mice recovered better than honokiol-treated or vehicle-receiving mice. Enhanced hindlimb locomotor functions in the trimebutine group were observed at 6 weeks after SCI. Immunohistology of the spinal cords rostral and caudal to the lesion site showed reduced areas and intensities of glial fibrillary acidic protein immunoreactivity in both trimebutine and honokiol groups, whereas increased regrowth of axons was observed only in the trimebutine-treated group. Both L1- and L1 mimetic-mediated intracellular signaling cascades in the spinal cord lesion sites were activated by trimebutine and honokiol, with trimebutine being more effective than honokiol. These observations suggest that trimebutine and, to a lesser extent under the present experimental conditions, honokiol have a potential for therapy in regeneration of mammalian spinal cord injuries.

Topics: Animals; Biphenyl Compounds; Cells, Cultured; Cerebellum; Female; Glial Fibrillary Acidic Protein; Gliosis; Intermediate Filaments; Lignans; Locomotion; Mice; Mice, Inbred C57BL; Neural Cell Adhesion Molecule L1; Neurons; Recovery of Function; Signal Transduction; Small Molecule Libraries; Spinal Cord Injuries; Trimebutine; Tubulin

Randomized experimental study.. To investigate the neuroprotective effect of honokiol (HNK) on rats subjected to traumatic spinal cord injury (SCI) and the molecular mechanisms.. Inflammation contributes to the secondary injury to the spinal cord. Honokiol has been used as a neuroprotective agent because of its strong antioxidant and anti-inflammatory properties. Kruppel-like factor 4 (Klf4) is a newly identified critical target for the anti-inflammatory effect of HNK. Whether HNK can inhibit inflammatory response in rat model of SCI through mediating the expression of Klf4 has yet to be elucidated.. Eighty-four adult female Sprague-Dawley rats were randomly divided into 4 groups as sham, SCI, SCI + Vehicle (0.1% propylene glycol in saline, intraperitoneally), and SCI + HNK (20 mg/kg, intraperitoneally) groups. The influences of HNK on the proinflammatory cytokines, microglial activation, neutrophil infiltration, histological changes, and improvement in motor function were assessed.. In the SCI group, proinflammatory cytokines, microglial activation, neutrophil infiltration, and Klf4 expression levels were increased compared with the sham group (P < 0.001). HNK intervention downregulated the expression of Klf4, reduced the production of proinflammatory cytokines, inhibited microglial activation, and neutrophil infiltration (P < 0.05). Furthermore, HNK also reduced histopathology and improved functional outcome after traumatic SCI.. HNK reduces secondary tissue damage and improves locomotor function recovery after SCI through suppressing inflammatory response, and can be used as a potential therapeutic agent for SCI.. NA.

Topics: Animals; Antioxidants; Biphenyl Compounds; Cytokines; Down-Regulation; Female; Inflammation; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lignans; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries