Factors related to improved American Spinal Injury Association grade of acute traumatic spinal cord injury

BACKGROUND Acute traumatic spinal cord injury(ATSCI)usually results in disability,yet data on contemporary national trends of ATSCI incidence are limited.AIM To provide a systematic and basic theoretical basis for improving the treatment of acute spinal cord injury.METHODS Data from the Peking University Third Hospital Inpatient Sample databases were analyzed.A total of 304 patients with ATSCI were included from 2012 to 2017.The epidemiological data,treatment,complications and clinical outcomes of these patients were reviewed.RESULTS Of the 304 patients,257(84.5%)were male,and 75%of the patients were 55 years old or younger.135 patients had improved follow-up American Spinal Injury Association(ASIA)grades(44.4%).Only 14 patients with ASIA grade A improved.A statistically significant difference in prognosis between patients who underwent surgery within 72 h and those who underwent surgery after 72 h was observed(P<0.05).Surgery within 72 h resulted in better prognosis.The Steroid group and the Non-Steroid group showed a significant difference in outcome among patients with ASIA grades A and B(P<0.05).Patients with pneumonia had a poorer prognosis than patients without pneumonia(P<0.05).Surgery within 72 h resulted in better prognosis.CONCLUSION This study found that there was no significant difference in hospitalization time and prognosis between the Steroid group and the Non-Steroid group,but the patients with severe spinal cord injury(ASIA grades A and B)who underwent surgery combined with steroid therapy had a better prognosis than those who underwent surgery alone.The disastrous consequences of ATSCI and lack of consensus on the management strategy are obvious.Further improvements in treatment planns are needed in order to obtain more reliable functional outcomes.

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's Diagnostic and Statistical Manual formulation with implications for treatment

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a system- atic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association＇s Diagnostic and Statistical Manual （DSM）. The major neuropsycholog- ical consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a DSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury

Surgical intervention combined with weight-bearing walking training improves neurological recoveries in 320 patients with clinically complete spinal cord injury:a prospective self-controlled study

Although a large number of trials in the SCI field have been conducted,few proven gains have been realized for patients.In the present study,we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury(SCI)subjects clinically diagnosed as complete or American Spinal Injury Association Impairment Scale(AIS)Class A(AIS-A).A total of 320 clinically complete SCI subjects(271 male and 49 female),aged 16–60 years,received early(≤7 days,n=201)or delayed(8–30 days,n=119)surgical interventions to reduce intraspinal or intramedullary pressure.Fifteen days post-surgery,all subjects received a weight-bearing walking training with the“Kunming Locomotion Training Program(KLTP)”for a duration of 6 months.The neurological deficit and recovery were assessed using the AIS scale and a 10-point Kunming Locomotor Scale(KLS).We found that surgical intervention significantly improved AIS scores measured at 15 days post-surgery as compared to the pre-surgery baseline scores.Significant improvement of AIS scores was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise comparisons of time points of 15 days,3 or 6 months indicating continued improvement in walking scores during the 6-month period.In conclusion,combining surgical intervention within 1 month post-injury and weight-bearing locomotor training promoted continued and statistically significant neurological recoveries in subjects with clinically complete SCI,which generally shows little clinical recovery within the first year after injury and most are permanently disabled.This study was approved by the Science and Research Committee of Kunming General Hospital of PLA and Kunming Tongren Hospital,China and registered at ClinicalTrials.gov(Identifier:NCT04034108)on July 26,2019.

Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmil training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were sub-jected to either step training on a treadmil or used in the model （control） group. The treadmil training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmil was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmil training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury.

Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury

Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.

Nischarin-siRNA delivered by polyethyleniminealginate nanoparticles accelerates motor function recovery after spinal cord injury

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2 a cells and primary cortical neurons.In recent years,more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury.We proposed that small interfering RNA targeting nischarin（Nis-si RNA） delivered by polyethyleneimine-alginate（PEIALG） nanoparticles promoted motor function recovery in rats with spinal cord injury.Direct microinjection of 5 μL PEI-ALG/Nis-si RNA into the spinal cord lesion area of spinal cord injury rats was performed.From day 7 after surgery,Basso,Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-si RNA group compared with the spinal cord injury group and PEI-ALG/Control-si RNA group.On day 21 after injection,hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-si RNA group.Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-si RNA group.These findings suggest that a complex of PEI-ALG nanoparticles and Nis-si RNA effectively suppresses nischarin expression,induces expression of growth-associated protein-43,and accelerates motor function recovery after spinal cord injury.

Nutech functional score: A novel scoring system to assess spinal cord injury patients

AIM To develop a new scoring system, nutech functional scores(NFS) for assessing the patients with spinal cord injury(SCI).METHODS The conventional scale, American Spinal Injury Association's(ASIA) impairment scale is a measure which precisely describes the severity of the SCI.However, it has various limitations which lead to incomplete assessment of SCI patients.We have developed a 63 point scoring system, i.e., NFS for patients suffering with SCI.A list of symptoms either common or rare that were found to be associated with SCI was recorded for each patient.On the basis of these lists, we have developed NFS.RESULTS These lists served as a base to prepare NFS, a 63 point positional(each symptom is sub-graded and get points based on position) and directional(moves in direction BAD → GOOD) scoring system.For non-progressive diseases, 1, 2, 3, 4, 5 denote worst, bad, moderate, good and best(normal), respectively.NFS for SCI has been divided into different groups based on the affected part of the body being assessed, i.e., motor assessment(shoulders, elbow, wrist, fingers-grasp, fingers-release, hip, knee, ankle and toe), sensory assessment, autonomic assessment, bed sore assessment and general assessment.As probability based studies required a range of(-1, 1) or at least the range of(0, 1) to be useful for real world analysis, the grades were converted to respective numeric values.CONCLUSION NFS can be considered as a unique tool to assess the improvement in patients with SCI as it overcomes the limitations of ASIA impairment scale.

Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase Ⅱ in spinal cord injury rats

Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase（ROCK） signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan（GV3）, Dazhui（GV14）, Zusanli（ST36） and Ciliao（BL32） and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the m RNA and protein expression of Rho-A and Rho-associated kinase Ⅱ（ROCKⅡ） of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKⅡ. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKⅡ. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of Rho A and ROCKⅡ. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

Effects of recombinant adeno-associated viruses expressing human vascular endothelial growth factor 165 on spinal cord injury

Numerous studies have confirmed that vascular endothelial growth factor （VEGF） improves the function of neural cells following spinal cord injury （SCI）. However, some studies have also verified that VEGF cannot significantly induce the increase in vascular density at or surrounding the lesion, and that VEGF therapy exacerbated secondary damage following SCI. Based on the dual effects of VEGF on SCI, we constructed the recombinant adeno-associated viruses （rAAV）-hVEGF165-IRES-human recombinant green fluorescent protein （hrGFP） （AAV-VEGF） and rAAV-IRES-hrGFP （AAV-GFP）. Our results suggested that rAAV expressed hVEGFles, and a low dose of VEGF relieved increased vascular permeability, improved microcirculation in the local spinal cord, lessened spinal cord edema, and decreased neuronal apoptosis. These results verified that the releasing effects of the rAAV virus vector had protective effects on the spinal cord.

Neurofilament 200 expression in a rat model of complete spinal cord injury following growth-associated protein-43 treatment

BACKGROUND： Growth-associated protein-43 （GAP-43） expression in the nervous system has been demonstrated to promote neural regeneration, neuronal growth and development, as well as synaptic reconstruction. Neurofilament 200 （NF200） expression could reflect degree of injury and repair in injured spinal axons. OBJECTIVE： To observe NF200 expression changes in a rat model of complete spinal cord injury following GAP-43 treatment and to explore the effects of GAP-43 following spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Kunming Medical University between March 2007 and October 2008. MATERIALS： GAP-43 and GAP-43 antibody were provided by Beijing Boao Biology, China; mouse anti-rat NF200 antibody was purchased from Chemicon, USA. METHODS： Female, 8-week-old, Sprague Dawley rats were randomly assigned into three groups following complete spinal cord injury, with 20 animals in each group： GAP-43 antibody, GAP-43, and model groups. In addition, each group was subdivided into four subgroups according to sampling time after modeling, Le., 3-, 5-, 9-, and 15-day groups, with 5 rats in each group. GAP-43 antibody or GAP-43 was injected into injury sites of the spinal cord, 5 μg/0.2 mL, respectively, twice daily for three consecutive days, followed by three additional days of injection, once daily. The model group did not receive any treatment following injury. MAIN OUTCOME MEASURES： NF200 expression in the damaged spinal area at different stages was detected by immunohistochemistry; lower limb motion function following injury was evaluated using the Basso, Beattie and Bresnahan （BBB） locomotor rating scale. RESULTS： NF200 expression was significantly reduced in the GAP-43 antibody group, compared with GAP-43 and model groups, at 3 and 5 days after spinal cord injury （P 〈 0.05）. In addition, the model group expressed significantly less NF200 than the GAP-43 group （P 〈 0.05）. BBB scores from the GAP-43 antibody and model groups were remarkably less than the GAP-43 group （P 〈 0.05）. At 9 and 15 days of injury after drug withdrawal, NF200 expression was increased in the GAP-43 antibody group, and NF200 expression and BBB scores in the GAP-43 antibody and GAP-43 groups were significantly greater than in the model group （P 〈 0.05）. In particular, the GAP-43 group exhibited greater BBB scores than the GAP-43 antibody group at day 9 （P 〈 0.05）. CONCLUSION： GAP-43 promoted NF200 expression and recovery of lower limb function. Early administration of GAP-43 antibody produced reversible nerve inhibition, which was rapidly restored following withdrawal.

Current and future surgery strategies for spinal cord injuries

Spinal cord trauma is a prominent cause of mortality and morbidity. In developed countries a spinal cord injury(SCI) occurs every 16 min. SCI occurs due to tissue destruction, primarily by mechanical and secondarily ischemic. Primary damage occurs at the time of the injury. It cannot be improved. Following the primary injury, secondary harm mechanisms gradually result in neuronal death. One of the prominent causesof secondary harm is energy deficit, emerging from ischemia, whose main cause in the early stage, is impaired perfusion. Due to the advanced techniques in spinal surgery, SCI is still challenging for surgeons. Spinal cord doesn't have a self-repair property. The main damage occurs at the time of the injury primarily by mechanical factors that cannot be improved. Secondarily mechanisms take part in the following sections. Spinal compression and neurological deficit are two major factors used to decide on surgery. According to advanced imaging techniques the classifications systems for spinal injury has been changed in time. Aim of the surgery is to decompress the spinal channel and to restore the spinal alinement and mobilize the patient as soon as possible. Use of neuroprotective agents as well as methods to achieve cell regeneration in addition to surgery would contribute to the solution.

Prognostic factors and its predictive value in patients with metastatic spinal cancer

BACKGROUND The spine is the most common location of metastatic diseases.Treating a metastatic spinal tumor depends on many factors,including patients’overall health and life expectancy.The present study was conducted to investigate prognostic factors and clinical outcomes in patients with vertebral metastases.AIM To investigate prognostic factors and their predictive value in patients with metastatic spinal cancer.METHODS A retrospective analysis of 109 patients with metastatic spinal cancer was conducted between January 2015 and September 2017.The prognoses and survival were analyzed,and the effects of factors such as clinical features,treatment methods,primary lesions and affected spinal segments on the prognosis of patients with metastatic spinal cancer were discussed.The prognostic value of Frankel spinal cord injury functional classification scale,metastatic spinal cord compression(MSCC),spinal instability neoplastic score(SINS)and the revised Tokuhashi score for prediction of prognosis was explored in patients with metastatic spinal tumors.RESULTS Age,comorbidity of metastasis from elsewhere,treatment methods,the number of spinal tumors,patient’s attitude toward tumors and Karnofsky performance scale score have an effect on the prognosis of patients(all P<0.05).With respect to classification of spinal cord injury,before operation,the proportion of grade B and grade C was higher in the group of patients who died than in the group of patients who survived,and that of grade D and grade E was lower in the group of patients who died than in the group of patients who survived(all P<0.05).At 1 mo after operation,the proportion of grade A,B and C was higher in the group of patients who died than in the group of patients who survived,and that of grade E was lower in patients in the group of patients who died than in the group of patients who survived(all P<0.05).MSCC occurred in four(14.3%)patients in the survival group and 17(21.0%)patients in the death group(P<0.05).All patients suffered from intractable pain,dysfunction in spinal cord and even paralysis.The proportion of SINS score of 1 to 6 points was lower in the death group than in the survival group,and the proportion of SINS score of 7 to 12 points was higher in the death group than in the survival group(all P<0.05).The proportion of revised Tokuhashi score of 0 to 8 points and 9 to 11 points were higher in the death group than in the survival group,and the proportion of revised Tokuhashi score of 12 to 15 points was lower in the death group than in the survival group(all P<0.05).Frankel spinal cord injury functional classification scale,MSCC,SINS and revised Tokuhashi score were important factors influencing the surgical treatment of patients with metastatic spinal cancer(all P<0.05).CONCLUSION Frankel spinal cord injury functional classification scale,MSCC,SINS and revised Tokuhashi score were helpful in predicting the prognosis of patients with metastatic spinal cancer.

Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu- bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine （an inhibitor and stimulator, respectively, of protein phosphatase 2A） for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi- tol 3-kinase （PI3K） and extracellular signal-regulated kinase 1/2 （ERK1/2） pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERKI/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro- tubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

创伤性颈脊髓损伤患者华勒氏变性的磁共振成像研究

目的探讨创伤性颈脊髓损伤患者脊髓华勒氏变性(WD)的磁共振成像(MRI)信号特点。方法回顾性分析2015年1月至2021年12月在北京博爱医院脊髓损伤康复科住院康复的191例创伤性颈脊髓损伤患者的临床资料,对常规颈椎MRI的矢状位及轴位T2加权像(T2WI)进行影像学评估,将其分为WD组和非WD组。比较两组性别、年龄、损伤机制、美国脊柱损伤协会残损分级(AIS)、神经平面、伤后获得MRI的时间差等,并分析WD在脊髓的背柱区(DC)、外侧脊髓丘脑束区(ST)和外侧皮质脊髓束区(CS)的信号特点。结果115例(60.2%)出现WD。WD组与非WD组年龄、损伤机制、AIS的等级分布和伤后获得MRI时间差有显著性差异(Z>3.820,χ2>9.104,P<0.05)。WD组中,在损伤部位的上方,DC、ST的WD发生率分别为100%和87%;在损伤部位的下方,CS的WD发生率为35.7%。根据WD信号出现的方式将其分为3组,只出现DC变化的15例(13%),DC合并ST发生变化为59例(51.3%),DC、ST、CS 3个位置均有变化的41例(35.7%)。3组间伤后获得MRI的时间差有显著性差异(H=90.794,P<0.05),3组间AIS等级分布无显著性差异(P>0.05)。结论创伤性颈脊髓损伤患者的常规MRI检查T2WI可检测到WD信号,且WD的发生与伤后时间存在关联。

上海脊髓损伤者社区康复需求状况及影响因素分析

目的:分析上海社区脊髓损伤者的康复需求状况及其影响因素。方法:研究对象是在上海阳光康复中心参加康复训练的上海常住脊髓损伤者。采用前期研制的社区康复需求评估表、社区融入问卷、自评焦虑及抑郁量表和自拟调查表收集数据。应用描述性统计、信效度分析和多元logistic回归进行统计分析。结果:280名社区脊髓损伤者纳入研究,其中65名参加复测研究。评估表内部一致性、复测信度、内容和结构效度都良好。探索性因子分析发现,15个评估条目分属于4个需求维度:教育/工作、社会、赋能和健康。总体社区康复需求程度为64.6%,低于60%的是教育/工作需求(55.3%)和社会需求(58.4%),其中需求比例在50%以下的7个需求条目是文化艺术活动(34.7%)、心理疏导(35.0%)、非正规教育(35.3%)、提升学历水平(41.9%)、体育活动(43.6%)、就业创业(43.7%)和娱乐休闲活动(48.6%)。多因素分析发现:高中及以下学历(OR=2.20)、户籍地外省市患者(OR=2.06)有心理疏导需求的可能性高;2018-2019年训练患者(OR=3.21)、大专及以上学历(OR=2.31)和患者中的社区康复指导员(OR=2.10)对非正规教育的需求比例更大;未婚/离异/丧偶(OR=2.24)、有工作/学生患者(OR=2.12)对提升学历水平需求更大;户籍地外省市患者(OR=2.72)、50岁以下(OR=2.84)和月收入低于6000元的患者(OR=3.63)对就业创业需求更大;社区康复指导员(OR=4.73和2.99)和女性(OR=1.83和2.49)患者更需要文化艺术和体育活动,受伤10年以上患者(OR=1.72)更需要文化艺术活动,完全损伤患者更需要体育活动(OR=1.90)。结论:上海社区脊髓损伤者的社区康复需求水平中等,其中赋能和健康需求较高,教育/工作和社会需求偏低。

以脊髓损害为首发症状的髓鞘少突胶质细胞糖蛋白抗体相关性疾病(附2例报道)

目的 探讨以脊髓损害为首发症状的髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)相关性疾病(MOGAD)的临床特点及免疫治疗效果。方法 回顾性分析2例脊髓损害为首发症状的MOGAD患儿的临床资料。结果 2例患儿均以双下肢乏力为首发症状,经外周血及CSF MOG-Ab检测、头颅及脊髓神经影像学检查后确诊为以脊髓损害为首发症状的MOGAD。糖皮质激素冲击治疗后临床症状缓解,复查影像学见异常信号范围缩小。出院后随访5月余临床治愈,症状无反复。结论 以脊髓损害为首发症状的MOGAD为少见疾病类型,其早期临床表现可能为颈背腰部不适、逐渐加重的肢体乏力及大小便障碍等,影像学表现可见多节段脊髓异常信号,CSF及外周血可检测出MOG-Ab。早期识别及诊断,并及时应用糖皮质激素冲击治疗有助于快速缓解临床症状、改善预后。

髓鞘相关抑制因子及其受体在脊髓损伤修复中的研究进展

脊髓损伤是一种严重的中枢神经系统创伤性疾病,常见于坠落伤、交通事故、重物砸伤等,可造成机体损伤平面以下的运动、感觉和自主神经功能障碍。髓鞘相关抑制因子(MAI)在损伤的脊髓微环境中具有促进生长锥塌陷、抑制轴突再生的作用,是造成脊髓损伤难以修复的主要原因。髓鞘相关抑制因子类蛋白,如神经轴突生长抑制因子(Nogo)、少突胶质细胞髓鞘糖蛋白(OMgp)和髓鞘相关糖蛋白(MAG),及其受体蛋白如Nogo-A/Nogo-66受体1(NgR1)、配对免疫球蛋白样受体B(PirB)、鞘氨醇-1-磷酸受体(S1PR2),均是脊髓微环境中的重要调节因子,可通过影响神经元轴突生长的信号通路抑制脊髓损伤的修复过程。虽然目前脊髓损伤修复的机制还不清楚,但调节髓鞘相关抑制因子类蛋白及下游信号通路是脊髓损伤修复的重要治疗途径之一。我们通过本文对近年来MAI类蛋白及其受体在脊髓损伤修复中的作用进行综述,为脊髓损伤修复提供可探究的新靶点,并为脊髓损伤后的临床治疗提供更多思路。

敲低黏膜相关淋巴组织淋巴瘤易位蛋白1对大鼠脊髓损伤炎症因子表达及神经功能的影响

目的 探讨黏膜相关淋巴组织淋巴瘤易位蛋白1(mucosa associated lymphoid tissue lymphoma translocation protein1,MALT1)对大鼠脊髓损伤(spinal cord injury,SCI)后神经炎症及神经功能恢复的影响。方法 选取96只SD(Sprague Dawley)大鼠,随机分成普通组及MALT1敲低组,普通组分为假手术组(n=24)、脊髓损伤组(SCI组)(n=24)。MALT1敲低组分为假手术组(n=12)、SCI组(n=12)、SCI注射慢病毒阴性对照组(SCI+NC组)(n=12)、SCI注射慢病毒MALT1敲除组(SCI+KD组)(n=12)。利用大鼠BBB(Basso、Beattie和Bresnahan,BBB)评分评估大鼠运动能力,苏木素-伊红(hematoxylin-eosin,HE)染色明确SCI程度,免疫蛋白质印迹法检测各组小鼠脊髓白细胞介素6(interleukin-6,IL-6)、白细胞介素10(interleukin-10,IL-10)、肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)和MALT1的表达。结果 与假手术组相比,SCI组大鼠MALT1表达、神经炎症指标均较高,而运动能力较差(均P<0.05)。在SCI+KD组大鼠中,MALT1敲低在造模后10~28d改善大鼠BBB评分,减轻神经损伤(P<0.05),炎症因子IL-1β、IL-6和TNF-α表达下降(均P<0.05),但不影响IL-10表达(P>0.05)。结论 MALT1敲低通过抑制SCI炎症因子表达,可改善脊髓功能恢复。

藏红花素对脊髓损伤大鼠运动功能、炎症的影响及机制研究

目的 探讨藏红花素对脊髓损伤大鼠运动功能、炎症及Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋蛋白激酶(ROCK)信号通路的影响。方法 构建脊髓损伤大鼠模型,将建模成功的48只大鼠随机分为模型组、藏红花素低(25 mg/kg)、高(50 mg/kg)剂量组、甲泼尼龙琥珀酸钠(30 mg/kg)组,每组12只;另取12只大鼠作为假手术组。各组给予对应药物干预14 d(每天1次)。评估大鼠运动功能,并采用苏木素-伊红和脱氧核糖核苷酸末端转移酶介导的缺口末端标记法染色分别观察脊髓组织病理变化和细胞凋亡,酶联免疫吸附试验法检测脊髓组织肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6水平;荧光定量PCR和蛋白质印迹法分别检测脊髓组织RhoA、ROCK1、ROCK2信使RNA(mRNA)和蛋白水平。结果 假手术组大鼠脊髓组织结构正常,无明显变化;与假手术组相比,模型组大鼠脊髓组织出现坏死灶,伴随嗜伊红色素颗粒生成,可见较多胶质瘢痕及空洞,BBB评分显著降低(P<0.05),脊髓组织细胞凋亡率、TNF-α、IL-1β、IL-6、RhoA、ROCK1、ROCK2 mRNA和蛋白水平显著升高(P<0.05);与模型组相比,藏红花素低、高剂量组大鼠脊髓组织病理损伤程度依次减轻,BBB评分依次升高(P<0.05),脊髓组织细胞凋亡率、TNF-α、IL-1β、IL-6、RhoA、ROCK1、ROCK2 mRNA和蛋白水平依次降低(P<0.05);甲泼尼龙琥珀酸钠组和藏红花素高剂量组大鼠脊髓组织病理变化程度及各项指标比较,差异均无统计学意义(P>0.05)。结论 藏红花素能改善脊髓损伤大鼠运动功能,抑制脊髓组织细胞凋亡和炎症反应,其机制可能与抑制RhoA/ROCK信号通路的激活有关。