Total flavonoids of hawthorn leaves promote motor function recovery via inhibition of apoptosis after spinal cord injury

Flavonoids have been reported to have therapeutic potential for spinal cord injury.Hawthorn leaves have abundant content and species of total flavonoids,and studies of the effects of the total flavonoids of hawthorn leaves on spinal cord injury have not been published in or outside China.Therefore,Sprague-Dawley rats were used to establish a spinal cord injury model by Allen's method.Rats were intraperitoneally injected with 0.2 m L of different concentrations of total flavonoids of hawthorn leaves(5,10,and 20 mg/kg)after spinal cord injury.Injections were administered once every 6 hours,three times a day,for 14 days.After treatment with various concentrations of total flavonoids of hawthorn leaves,the Basso,Beattie,and Bresnahan scores and histological staining indicated decreases in the lesion cavity and number of apoptotic cells of the injured spinal cord tissue;the morphological arrangement of the myelin sheath and nerve cells tended to be regular;and the Nissl bodies in neurons increased.The Basso,Beattie,and Bresnahan scores of treated spinal cord injury rats were increased.Western blot assays showed that the expression levels of pro-apoptotic Bax and cleaved caspase-3 were decreased,but the expression level of the anti-apoptotic Bcl-2 protein was increased.The improvement of the above physiological indicators showed a dose-dependent relationship with the concentration of total flavonoids of hawthorn leaves.The above findings confirm that total flavonoids of hawthorn leaves can reduce apoptosis and exert neuroprotective effects to promote the recovery of the motor function of rats with spinal cord injury.This study was approved by the Ethics Committee of the Guangxi Medical University of China(approval No.201810042)in October 2018.

Prediction of motor recovery after ischemic stroke using diffusion tensor imaging： A meta-analysis

BACKGROUND: This systematic review aims to investigate the prediction value of diffusion tensor imaging for motor function recovery of ischemic stroke patients.METHODS: Cochrane Central Register of Controlled Trials(CENTRAL)(the Cochrane Library 2016, Issue 9), Pub Med, Embase, Clarivate Analytics, Scopus, CINAHL, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Google Scholar were searched for either motor recovery or corticospinal tract integrity by diffusion tensor imaging in different stroke phase from January 1, 1970, to October 31, 2016. The study design and participants were subjected to metrological analysis. Correlation coeffi cient(r) was used for evaluating the relationship between fractional anisotropy(FA) and motor function outcome. Correlation coeffi cient values were extracted from each study, and 95% confidence intervals(CIs) were calculated by Fisher's z transformation. Meta-analysis was conducted by STATA software.RESULTS: Fifteen studies with a total of 414 patients were included. Meta-analysis showed that FA in the subacute phase had the signifi cant correlation with motor function outcome(ES=0.75, 95%CI 0.62–0.87), which showed moderate quality based on GRADE system. The weight correlation coeffi cient revealed that an effect size(ES) of FA in acute phase and chronic phase was 0.51(95%CI 0.33–0.68) and 0.62(95%CI 0.47–0.77) respectively.CONCLUSION: This meta-analysis reveals that FA in the subacute phase after ischemic stroke is a good predictor for functional motor recovery, which shows moderate quality based on the GRADE system.

Neuroprotective effect of immunomodulatory peptides in rats with traumatic spinal cord injury

Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI.The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor(MLIF), A91 peptide, and glutathione monoethyl ester(GSH-MEE) on chronic-stage spinal cord injury.Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion.Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE.Two months after injury, motor functional recovery was evaluated using the open field test.Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively.The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively.Collagen deposition was evaluated using Masson's trichrome staining.The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area.The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI.This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116(approval date November 30, 2015) and R-2017-3603-33(approval date June 5, 2017).

Acellular nerve grafts supplemented with induced pluripotent stem cell-derived exosomes promote peripheral nerve reconstruction and motor function recovery

Peripheral nerve injury is a great challenge in clinical work due to the restricted repair gap and weak regrowth ability.Herein,we selected induced pluripotent stem cells(iPSCs)derived exosomes to supplement acellular nerve grafts(ANGs)with the aim of restoring long-distance peripheral nerve defects.Human fibroblasts were reprogrammed into iPSCs through non-integrating transduction of Oct3/4,Sox2,Klf4,and c-Myc.The obtained iPSCs had highly active alkaline phosphatase expression and expressed Oct4,SSEA4,Nanog,Sox2,which also differentiated into all three germ layers in vivo and differentiated into mature peripheral neurons and Schwann cells(SCs)in vitro.After isolation and biological characteristics of iPSCs-derived exosomes,we found that numerous PKH26-labeled exosomes were internalized inside SCs through endocytotic pathway and exhibited a proliferative effect on SCs that were involved in the process of axonal regeneration and remyelination.After that,we prepared ANGs via optimized chemical extracted process to bridge 15 mm long-distance peripheral nerve gaps in rats.Owing to the promotion of iPSCs-derived exosomes,satisfactory regenerative outcomes were achieved including gait behavior analysis,electrophysiological assessment,and morphological analysis of regenerated nerves.Especially,motor function was restored with comparable to those achieved with nerve autografts and there were no significant differences in the fiber diameter and area of reinnervated muscle fibers.Taken together,our combined use of iPSCs-derived exosomes with ANGs demonstrates good promise to restore long-distance peripheral nerve defects,and thus represents a cell-free strategy for future clinical applications.

Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17^(+) γδ T cells

Spinal cord injury(SCI)causes motor,sensory,and autonomic dysfunctions.The gut microbiome has an important role in SCI,while short-chain fatty acids(SCFAs)are one of the main bioactive mediators of microbiota.In the present study,we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI.Allen’s method was utilized to establish an SCI model in Sprague-Dawley(SD)rats.The animals received water containing a mixture of 150 mmol/L SCFAs after SCI.After 21 d of treatment,the Basso,Beattie,and Bresnahan(BBB)score increased,the regularity index improved,and the base of support(BOS)value declined.Spinal cord tissue inflammatory infiltration was alleviated,the spinal cord necrosis cavity was reduced,and the numbers of motor neurons and Nissl bodies were elevated.Enzyme-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and immunohistochemistry assay revealed that the expression of interleukin(IL)-10 increased and that of IL-17 decreased in the spinal cord.SCFAs promoted gut homeostasis,induced intestinal T cells to shift toward an anti-inflammatory phenotype,and promoted regulatory T(Treg)cells to secrete IL-10,affecting Treg cells and IL-17^(+)γδT cells in the spinal cord.Furthermore,we observed that Treg cells migrated from the gut to the spinal cord region after SCI.The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17^(+)γδT cells in the spinal cord,which inhibits the inflammatory response and promotes the motor function in SCI rats.Our findings suggest that there is a relationship among gut,spinal cord,and immune cells,and the“gut-spinal cord-immune”axis may be one of the mechanisms regulating neural repair after SCI.