Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

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+ γδ T 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+ γδ T 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.

Extremely low frequency magnetic exposure attenuates oxidative stress and apoptotic cell death in injured spinal cord of rats

Secondary spinal cord injury (SCI) sets on immediately after trauma which results in vascular, morphological and biochemical changes at the site of lesion. Amongst these, the crucial events such as oxidative stress and apoptosis result in spreading the injury to adjacent tissues following the initial insult. Exposure to extremely low frequency magnetic field (ELFMF) is reported to modulate oxidative stress and cell death in vivo. Here, we investigated the influence of ELFMF on oxidative stress and cell death after SCI. Adult male Wistar rats were divided into Sham-SCI (Laminectomy only), Sham-SCI+MF (ELFMF exposure; 17.96 ?T intensity, 50 Hz frequency, 2 h duration/day to Sham-SCI rats), SCI (complete transection of T13 spinal cord) and SCI+MF (ELFMF exposure to SCI rats) groups. They were sacrificed on day 2 for antioxidant assay and day 1, 2 and 3 for cell death study. The oxidative stress was assessed by antioxidant enzyme activities and the cell death was assessed by TUNEL assay and Caspase-3 immnuohistochemistry. Data revealed significant reduction in the lipid peroxidation and number of cells undergone cell death besides improvement in antioxidant levels in the spinal cord of ELFMF exposed SCI rats. These novel findings demonstrate the potential of ELFMF to attenuate oxidative stress and cell death in the early stage of secondary injury process after SCI.

Protocol paper: kainic acid excitotoxicity-induced spinal cord injury paraplegia in Sprague-Dawley rats

BACKGROUND: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. METHODS: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. RESULTS: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. CONCLUSIONS: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

Intestinal dysfunction of spinal cord injury treated with moxibustion: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect on intestinal dysfunction of spinal cord injury (SCI) between the comprehensive therapy of moxibustion (moxibustion for opening the governor vessel and regulating the spirit) and rehabilitation training and the simple treatment with rehabilitation training.@*METHODS@#A total of 60 patients with intestinal dysfunction of SCI were randomized into a comprehensive therapy group and a rehabilitation group, 30 cases in each one (3 cases were dropped out in each group). On the base of the routine western medicine treatment and rehabilitation training, the bowel training and rectal function training were provided, once a day in the rehabilitation group. In the comprehensive therapy group, on the base of the treatment as the rehabilitation group, the moxibustion was exerted at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Dazhui (GV 14) and Baihui (GV 20), etc, once a day, 30 min each time. In both groups, the treatment for 4 weeks was as one course and 3 courses of treatment were required. Separately, before treatment, after 4, 8 and 12 weeks of treatment, the scores of neurogenic bowel dysfunction (NBD) and World Health Organization quality of life scale (WHOQOL-BREF) were observed and the clinical effect was evaluated after 12 weeks of treatment.@*RESULTS@#After treatment, the total effective rate was 88.9% (24/27) in the comprehensive therapy group, which was higher than 74.1% (20/27) in the rehabilitation group (<0.05). After 4, 8 and 12 weeks of treatment, NBD scores were all reduced obviously as compared with those before treatment in the two groups (all <0.01). After 8 and 12 weeks of treatment, NBD scores in the comprehensive therapy group were lower than the rehabilitation group (both <0.05). After 4, 8 and 12 weeks of treatment, the scores of all of the domains (psychology, physiology, social relations and environment) in WHOQOL-BREF were higher than those before treatment in the two groups (all <0.01). After 4 weeks of treatment, the scores in the psychology and physiology domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05). After 8 and 12 weeks of treatment, the scores of all of the domains in the comprehensive therapy group were higher than the rehabilitation group (all <0.05).@*CONCLUSION@#The comprehensive treatment of moxibustion and rehabilitation training achieves the better effect on intestinal dysfunction of SCI than the simple rehabilitation training and greatly improves the quality of life in SCI patients.

Study on the clinical application of the intervention program of bowel dysfunction in patients with spinal cord injury / 上海交通大学学报（医学版）

Objective • To verify the effectiveness of the intervention program of bowel dysfunction in patients with spinal cord injury (SCI). Methods • Eighty bowel dysfunction patients with SCI in a rehabilitation hospital in Shanghai from Jan. to Dec. 2018 were included. According to the time of admission, the patients were divided into intervention group and control group, with 40 cases in each group. The patients in the control group received the routine nursing, and the patients in the intervention group were provided with the intervention program constructed by this study. The bowel function indexes of the two groups were compared at the time of admission, 4 weeks after intervention and 1 month after discharge. The quality of life in the two groups was compared at the time of admission and 1 day before discharge. Results • After intervention, the defecation frequency, fecal character score, defecation time, abdominal distention, constipation rate and drug dependence rate of the intervention group were lower than those of the control group (all P<0.05), and their total scores of quality of life and the scores in various fields were higher than those of the control group (all P<0.05). The differences in the quality of life between the two groups of patients after intervention and at the time of admission were statistically significant except for the social field (all P<0.05). Conclusion • The intervention program for bowel dysfunction patients with SCI can effectively lead to the recovery of the bowel function, reduce the incidence of bowel complications, and improve the quality of their life.

Comprehensive therapeutics targeting the corticospinal tract following spinal cord injury / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.

Effect of Danshen injection on expression of brain-derived neurotrophic factor and insulin-like growth factor-1 in rats with spinal cord injury / 上海交通大学学报（医学版）

Objective: To explore the mechanism of Danshen injection on promoting spinal cord functional recovery by observing the expression of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) in rats with spinal cord injury (SCI). Methods: Thirty SD rats were divided randomly into normal control group, model group and treatment group (n=10). The rats in model group and treatment group were subjected to weight-drop SCI according to the Allens' method, and administered normal saline and Danshen injection, at the dosage of 1 mL/kg once a day, by intraperitoneal injection respectively for 14 days. The combine behavioral score (CBS) of rats in all groups was detected on 1, 3, 7 and 14 days after SCI, the expression of BDNF and IGF-1 in all groups was detected with immunohistochemical method and Western blotting. Results: Compared with the normal control group, the CBS in model group and treatment group was elevated after SCI, and declined gradually with the lapse of injury time in different rates. Until 14 days after SCI, compared with the model group, the CBS in treatment group was lower (P=0.000), and the expression levels of BDNF and IGF-1 (including immunohistochemistry positive cell number and relative content) in treatment group were both elevated significantly (all P<0.05). Conclusion: Danshen injection can promote the recovery of nerve function by elevating the expression of BDNF and IGF-1 after SCI.

Botulinum neurotoxin serotype A heavy chain intervenes in the H3 acetylation: A preliminary study / 中国比较医学杂志

Objective To investigate the effect and molecular mechanism of botulinum neurotoxin serotype A (BoNT/A) heavy chain on neuron regeneration. Methods Cell culture, rats, immunofluorescence, SDS-PAGE and western blot, etc. were adopted in this study to explore the alterations of histone-3 acetylation (acetyl-H3 ) by local treatment of BoNT/A heavy chain to spinal cord injury (SCI) in rats (in vivo) or by adding it into cell culture (in vitro). Meanwhile, the relevance of acetyl-H3 to neurite out-growth based on SCI and cell culture with BoNT/A heavy chain application was approached as well. Results The application of BoNT/A heavy chain to cultured Neuro-2a cells increased the level of H3 acetylation. The increase of H3 acetylation was paralleled with the growth of neuritogenesis. Also, the neuronal treatment of BoNT/A heavy chain to SCI promoted the re-growth of neuronal processes surrounding the lesions. The growth of neuronal processes was positively correlated to the level of H3 acetylation. During the periods of BoNT/A heavy chain treatment in vivo or in vitro, the increase of H3 acetylation showed two peaks. Conclusions BoNT/A heavy chain increased the H3 acetylation, which might be one of its neuritogenic mechanisms.

Effect of Danshen injection on expression of brain-derived neurotrophic factor and insulin-like growth factor-1 in rats with spinal cord injury / 上海交通大学学报（医学版）

Objective·To explore the mechanism of Danshen injection on promoting spinal cord functional recovery by observing the expression of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) in rats with spinal cord injury (SCI). Methods·Thirty SD rats were divided randomly into normal control group, model group and treatment group (n=10). The rats in model group and treatment group were subjected to weight-drop SCI according to the Allens' method, and administered normal saline and Danshen injection, at the dosage of 1 mL/kg once a day , by intraperitoneal injection respectively for 14 days. The combine behavioral score (CBS) of rats in all groups was detected on 1, 3, 7 and 14 days after SCI, the expression of BDNF and IGF-1 in all groups was detected with immunohistochemical method and Western blotting. Results·Compared with the normal control group, the CBS in model group and treatment group was elevated after SCI, and declined gradually with the lapse of injury time in different rates. Until 14 days after SCI, compared with the model group, the CBS in treatment group was lower (P=0.000), and the expression levels of BDNF and IGF-1 (including immunohistochemistry positive cell number and relative content) in treatment group were both elevated significantly (all P<0.05). Conclusion·Danshen injection can promote the recovery of nerve function by elevating the expression of BDNF and IGF-1 after SCI.

Reviews on acupuncture for cellular signal transduction in spinal cord injury / 中国针灸

Investigating the influence of acupuncture on cellular signal transduction is an efficient pathway to reveal the action mechanism of acupuncture on spinal cord injury (SCI). In this study, the experiment research literature regarding acupuncture for SCI during past 10 years was reviewed and analyzed. As a result, it was found that acupuncture could regulate the expression of the first intercellular messenger as well as the second signal molecules including cyclic adenosine monophosphate, cyclic guanosine monophosphate, Ca2+, nitric oxide to intervene the apoptotic signaling pathway, Rho/Rock signaling pathway, Wnt signaling pathway, MAPK signaling pathway, Notch signaling pathway, etc., which could improve regeneration and repair of SCI. In conclusion, in future researches more attention should be paid to the cellular signal transduction networks and different effects among various acupoint combinations and acupuncture modalities on cellular signal transduction, which have an essential role for revelation of clinical application rules and optimization of clinical treatment protocol.

Effects of embryonic neural stem cells on trauma of red nucleus neurons of the rats with spinal cord injury after transplantion / 基础医学与临床

Objective To study the effects of embryonic neural stem cells transplantion on trauma of red nucleus neu-rons of the rats with spinal cord injury.Methods NSCs in logarithmic phage were labeled with BrdU,a Sprague Dawley rat mode of spinal cord injury (SCI) was developed with electrocircuit control spinal cord injuring device.Thirty SD rats were randomly divided into three groups: sham group,SCI group and NSC group.The NSCs were trans-planted into injured site three days after SCI.Then NSCs labeled with Brdu were detected by immunohistochemisty,rubrospinal tract (RST) neurons were labeled by retrograde transport of the horseradish peroxidase (HRP) from the lesion site,which were taken by damaged axons and remained in the neurons,then the labeled red nucleus (RN) neurons were counted.Hind limb function of experimental rats was evaluated by a blinder observer using BBB open field locomotion rating score.Results BrdU positive NSCs were detected in the spinal cord after transplantation,the number of RST neurons labeled by HRP in NSC group was more than that in SCI group (P <0.01),the BBB score of NSC group was higher than SCI group (P <0.01).Conclusion The transplanted NSCs can survive in the injured site of spinal cord and protect RN,then promote more remarkably functional recovery after SCI.

Reproductive Dysfunction in Men with Spinal Cord Injury (review) / 中国康复理论与实践

@#After spinal cord injury (SCI), the male reproductive functions are often seriously impaired, including dysfunction of erection, ejaculation, and abnormality of sperm qualities. With the advance of medicine, nowaday most men with SCI can finish erection, ejaculation and assisted reproduction. This article reviewed the reproductive dysfunctions in men with SCI, and discussed the relevant aspects.

Astrocyte Proliferation and Glial Scar Formation after Spinal Cord Injury (review) / 中国康复理论与实践

@#The nature and functions of astrocytes (AS)， the pathological changes and roles of AS after spinal cord injury， the experimental methods of inhibiting AS proliferation and glial scar formation， and so on, were reviewed. AS beneficially affects repairing injured spinal cord at different periods of differentiation. However， adult AS secreting the factors formed the chemical glial barrier which severely affects nerve regeneration and hinders axon extension. Because of the static， activated and proliferative AS tending to coexist after spinal cord injury， and complex factors of barrier formation， the current approach taken by a single method is difficult to effectively control the AS proliferation and glial scar formation.

Relationship between Level of Thoracic Complete Spinal Cord Injury and Ambulatory Function with Reciprocating Gait Orthosis through 3D Gait Analysis / 中国康复理论与实践

@#ObjectiveTo evaluate the relationship between the level of thoracic complete spinal cord injury(SCI) and ambulatory function wearing Reciprocating Gait Orthosis(RGO) through three dimentional gait analysis, and to explore the quantitative indicators of reconstructing walking capacity of thoracic complete SCI patients.Methods10 patients with thoracic complete spinal cord injury of lesion level from T4 to T12 who had experienced RGO gait training for at least 3 months. Three dimentional gait analysis system of Vicon Nexus 1.2 was used to test and examine the gait speed, cadence, stride length, pelvic angle of rotation, hip range of motion(ROM), crutch force, angular velocity of hip flexion and extension phases, etc. Pearson's product moment correlation coefficient and Spearman rank correlation coefficient were used to examine the relationship between the level of spinal cord injury and the kinematic and kinetic values.ResultsThe mean cadence and stride length were (37.4±2.15) steps/min and (91.6±9.09) cm. The mean hip ROM, angular velocity of hip flexion and extension phases were (42.57 °±5.43 °), (20.88 °±2.18 °)/s and (124.75 °±9.31 °)/s respectively. The gait speed, stride length, peak crutch force, hip ROM, mean crutch force and angular velocity of hip extension phase all had significant pertinence with the level of spinal cord injury.ConclusionThe limitation of hip ROM and excessive load of upper limbs mainly result in ambulatory disorder in higher thoracic complete SCI patients who should be undertaken some rehabilitation training to reduce excessive physiological load in order to improve their ambulatory capacity.

Recovery of Motor Function and Changes of Anterior Horn Cells after Spinal Cord Injury in Rats / 中国康复理论与实践

@#Objective To explore the restoration of motor function and the expression of calcitonin gene-related peptide(CGRP)and acetylcholine esterase(AChE)in the anterior horn motoneurons after different types of spinal cord injury.Methods 60 adult female Wistar rats were randomly assigned to 3 groups:sham group,completely transection group and contusion group.Average combined scores(ACOS)were applied to assess the motor function at various time after the surgery.The content of AChE in the anterior horn of L2-L4 was detected with Karnovsky-Roots staining and the expression of CGRP was then determined with immunohistochemistry.Results The scores of ACOS were much higher in the contusion group than in the transection group at each time point examined.The content of both AChE and CGRP significantly decreased after either type of spinal cord injury.However,their activity gradually recovered to the normal level in the contusion group,but not in the transection group.Moreover,the changes of CGRP occurred earlier than those of AChE.Conclusion There is strong relationship between the motor function recovery and the functional state of anterior horn cells.CGRP or AChE may play an important role in the functional recovery of locomotion after spinal cord injury in rats.

Prevention and Treatment of Complications of Spinal Cord Injury / 中国康复理论与实践

@#The complications of spinal cord injury(SCI)affect not only the rehabilitation treatment,but also quality of the patients' living,even threaten to patients' life,including pressure sore,complications of urinary system and respiratory system,deep venous thrombosis,pulmonary embolism,spasm,pain,autonomic dysreflexia,osteoporosis,etc.The prevention and treatment of complications of SCI may be helpful to improve patients' health,and a premise of the rehabilitation.

Rehabilitation Therapies of Spinal Cord Injury / 中国康复理论与实践

@#This article mainly introduced the basic strategy of rehabilitation of spinal cord injury,including maintaining and improving range of motor(ROM),enhancing the muscle strength,sitting and standing balance training,respiration training,application of splints and aids.The rehabilitation objectives and approaches of each level of spinal cord injuries were also involved.

Changes of Calcitonin Gene-related Peptide and Acetylcholine Esterase in Motor End Plates after Spinal Cord Injury in Adult Rats / 中国康复理论与实践

@#Objective To explore the degeneration of motor end plates (MEP) by observing the expression of calcitonin gene-relative peptide (CGRP) and acetylcholine esterase (AChE) in the MEP after different types of spinal cord injury. Methods 60 adult female Wistar rats were randomly assigned to 3 groups: sham group, completely transection group and contusion group. The content of AChE in the MEP was detected with Karnovsky-Roots staining and the expression of CGRP was then determined with immunohistochemistry. Results The content of both AChE and CGRP significantly decreased after either type of spinal cord injury. However, their activity gradually recovered to the normal level in the contusion group, but not in the transection group. Moreover, the changes of CGRP occurred earlier than those of AChE. Conclusion The motor end plate degenerates differently after different kinds of spinal cord injury in adult rat, CGRP and AChE are related to the degeneration of MEP.

Intravenously Injected Bone Marrow Mesenchymal Stem Cells Can Promote Recovery of Bladder Function after Spinal Cord Injury (review) / 中国康复理论与实践

@#The feasibility and mechanism study on intravenously injected bone marrow mesenchymal stem cells (MSCs) improving bladder function after spinal cord injury (SCI) were discussed by review the biological characteristics of MSCs, the changes and mechanism of the lower urinary tracts after SCI, and the study on the MSCs promoting recovery of bladder function.

The experimental observation on the repairing spinal cord injury by olfactory ensheathing cells allograft of different sources / 药物分析学报

Objecttive To observe the repaired effect of distinct source olfactory ensheathing cells (OECs) on spinal cord injury (SCI) rats. Methods These OECs were dissociated from olfactory bulb and olfactory mucosa of SD rats and transplanted to the injuried region of spinal cord injury rats. The function of nerve, motor evoked potential of hind legs and the histopathlogical diversities of injuried spinal cord were observed. Results The OECs grafts into the SCI area could survive longer time. The BBB scale, incubation stage of EP and histopathologic manifestations showed that the group with transplanted OECs regained more improvement in hindlimb than the control group. Conclusion The OECs of two sources have the same ability to regain and improve the axonal function which can promote axons regeneration of SCI.