Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Effect of platelet activating factor on blood spinal cord barrier following cervical cord injury

Effect of platelet activating factor(PAF) on blood spinal cord barrier in cervical cord injury was investigated. Methods: Spinal cord injury at C6 segment was induced with Allen’s ’method in cats. PAF and PAF receptor antagonist BN52021 were administered by arachnoid space and intravenous injection respectively, and their effects on PAF levels, blood spinal cord barrier and cervical cord edema in the injuried zone and adjacent cervical cord tissue following cervical cord injury were investigated. Results: PAF levels, Evens content and water content in the injuried and adjacent cervical cord tissues significantly increased following trauma. PAF levels, Evens content and water content were evidently elevated with PAF by arachnoid space injection. PAF receptor antagonist BN52021 could inhibit the increase in PAF levels and reduce Evens and water content in the cervical cord tissue following trauma. Conclusion: PAF is an important contributing factor causing post-traumatic damage to the blood spinal cord barrier, while PAF receptor antagonist can effectively relieve post-traumatic damage to the blood spinal cord barrier.

Changes of blood flow in spinal cord following ischemia and reperfusion and its relation with pathological damages in rabbits

objective: To investigate the changes of spinal cord blood flow (SCBF) after the ischemia and reperfusion injury of the spinal cord and its relation with pathological damages. Methods: Twenty adult Japanese big-ear white rabbits equally randomized into the control group, 30-min-ischemic group, 60-min-is chemic group and 90-min-ischemic group. All the rabbits in the latter 3 groups were inflicted with the is chemia and reperfusion injury of the spinal cord through selective occlusion of the lumbar artery. SCBF was measured with the hydrogen clearance method and the pathological changes of the injured spinal cord were observed with Nissl’s staining. Results: SCBF during ischemia was 0 ml/100 g/min. During reperfusion, it was recovered to different levels. However, it was still decreased as compared with that before ischemia and that in the control group. The pathological changes of the gray matter were the most significant. The severi ty of the pathological changes decreased in the order from 90-min-ischemic group, 6O-min-ischemic group to 30-min ischemic group. Conclusion: Reversible injury occurs in rabbits after ischemia for 30 min, irreversible injury in those after ischemia for 90 min and partially reversible injury in those after ischemia for 60 min.

Effects of spinal cord stimulation on cerebrovascular flow: role of sym-pathetic and parasympathetic innervations

Objective Cervical spinal cord stimulation （SCS） has been found to augment cerebral blood flow （CBF） in a number of animal models. However, the effective use of SCS is hampered by a lack of understanding of its mechanism（s） of action. In this paper, we focus on the sympathetic and parasympathetic effects of SCS on CBF. Method SpragueDawley rats were selected for the experimental series. The animals were divided into 5 groups to underwent SCS and laser Doppler flowmeter （LDF） recordings. Control group, the animal underwent SCS and LDF recordings without any surgery of the nerve fibers and ganglia. V 1 group, the animal underwent bilateral resection of the nasociliary and post-ganglionic parasympathetic nerve fibbers. SCG group, the animal underwent bilateral resection of supper cervical ganglion. V 1 ＋ SCG group, the animal underwent both surgeries as V1- and SCG-group animals did. Sham group, the animal underwent the carotid manipulation with blunt-tipped forceps as well as the dissection of nasociliary and post-ganglionic parasympathetic nerve fibers around the ethmoidal foramen, but without cutting any nerves. Results During the SCS, the LDF was no statistical difference between the V 1 or SCG group and the control group. Yet, the effects of SCS on CBF are completely abolished in V1＋ SCG group. Conclusions Surgical interruption of both the parasympathetic and sympathetic pathways has the contradict effect on SCS-induced CBF augmentation.

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Electrical fields and the promotion of endogenous angiogenesis in a rat spinal cord injury model

BACKGROUND： Previous studies have shown that direct current electrical fields affect development and growth of human microvascular endothelial cells, but the role of electrical fields on promoting angiogenesis in tissues following spinal cord injury remains poorly understood. OBJECTIVE： To determine the effects of electrical fields on angiogenesis and spinal cord repair following traumatic spinal cord injury in rats. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Chongqing Key Laboratory of Neurology, Affiliated Hospital of Chongqing Medical University, China from September 2007 to August 2008. MATERIALS： Hydrogen blood flow detector （Soochow University Medical Instrument, China）, Power Lab System （AD Instruments, Colorado Springs, CO, USA） and mouse anti-vascular endothelial growth factor （VEGF） monoclonal antibody （Sigma-Aldrich, St. Louis, MO, USA） were used in this study. METHODS： A total of 60 healthy, adult, Sprague Dawley rats were equally and randomly assigned to sham-surgery, model, and electrical field groups. The Allen＇s weight-drop method was used to induce complete spinal cord injury in the model and electrical field groups. Rats in the electrical field group were implanted with silver needles and electrical fields （350 V/m） were applied following traumatic injury. MAIN OUTCOME MEASURES： Latency of somatosensory-evoked potential was detected and spinal cord blood flow was measured by hydrogen blood flow detector. Microvascular density was determined by histological analysis. VEGF expression in the spinal cord was observed by immunohistochemical staining. RESULTS： Recovery of spinal cord blood flow was significantly increased in the electrical field group （at 1, 2, 4, 8, and 24 days after injury） compared with the model group （P 〈 0.05 or P 〈 0.01）. Latency of P1 waves in somatosensory-evoked potential of electrical field group （at 1,2, 4, 8, and 24 days after injury） was significantly shorter than the model group （P 〈 0.05 or P 〈 0.01）. Microvascular density and VEGF expression were greater in the electrical field group compared with the model group at 24 days after injury （P 〈 0.01）. CONCLUSION： Electrical fields （350 V/m） promoted angiogenesis within injured rat tissue following spinal cord injury and improved spinal cord function. Electrical fields could help to ameliorate spinal cord injury. The mechanisms of action could be related to increased VEGF expression.

EFFECTS OF ACUPUNCTURE AT FENGCHI POINT (GB 20) ON CEREBRAL BLOOD FLOW

Blood velocity in the vertebral artery and the basilar artery was observed before and after acupuncture at Fengchi point (GB 20) in 97 patients by transcranial Doppler ultrasonic detecting. The results showed that the blood velocity in patients with either high or low blood flow had significant changes after acupuncture (P

不同运动方式促进周围神经损伤后的功能恢复

背景:运动作为一种主动康复的方式可以改善周围神经损伤导致的功能障碍,而不同运动方式针对的病变部位及恢复机制不同。目的:综合分析不同运动方式在周围神经损伤功能恢复中的应用及机制。方法:应用计算机检索中国知网、PubMed数据库建库时间至2024年1月期间的相关文献,英文检索词为“peripheral nerves injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training”,中文检索词为“周围神经损伤,脊髓,大脑皮质,肌肉萎缩,有氧运动,血流限制,镜像运动”,最终纳入77篇文献进行分析。结果与结论:周围神经损伤后会引起其支配骨骼肌萎缩、相应脊髓节段病变、感觉运动皮质重塑等系统性的病理变化。有氧运动可以加强免疫反应,促进神经胶质细胞极化以及神经生长因子的释放,改善功能障碍。血流限制运动可以调节肌肉生长因子的分泌,促进肌肉生长及增强肌肉力量。镜像运动在激活大脑皮质、减少皮质重塑方面有良好的作用。不同运动方式在周围神经损伤功能恢复中具有潜在的益处,然而目前仍存在一些问题和挑战,例如运动方式的选择、运动强度和频率的控制及机制的详细解析等。

Clinical effects of innovative tuina manipulations on treating cervical spondylosis of vertebral artery type and changes in cerebral blood flow

OBJECTIVE:To determine the clinical effect,treatment times,and rheoencephalogram changes in vertebral artery type cervical spondylosis patients treated with innovative Tuina manipulations.METHODS:One hundred and twenty six cervical spondylosis patients(vertebral artery type) were randomly divided into test and control groups.Patients in the test group were treated with innovative Tuina manipulations,while those in the control group were treated with the routine Tuina manipulations according to the textbook of Chinese Massage for Acupuncture and Moxibustion majors.The clinical effects,treatment times,clinical symptoms,and cerebral blood flow were measured.RESULTS:The response to the treatment was 100% in the test group and 88.71% in the control group.Patients in the test group required(7 ± 4) treatments before recovery,while those in the control group required(15 ± 7) treatments before recovery(P<0.05).The clinical symptoms exhibited greater improvement in the test group compared to the control group(P<0.05).There were no differences in cerebral blood flow between the two groups.CONCLUSION:Both innovative Tuina manipulations and routine Tuina manipulations produced satisfactory therapeutic results in vertebral artery type cervical spondylosis patients.However,the innovative manipulation was more effective in improving the functional symptoms,although there were no changes in the cerebral blood flow.

脊髓损伤后体位性低血压的临床研究

目的:探讨高位脊髓损伤患者发生体位性低血压(OH)的临床机制。方法:对45例高位脊髓损伤患者进行30°、60°、80°斜立试验,测量斜立后血压、脉搏、大脑中动脉血流(CBF)速度。根据斜立后是否出现体位性低血压症状,将患者分为有症状组和无症状组,进行对比性分析。结果:第1组24例患者无OH症状,能完成全部的测试;第2组21例患者均出现OH症状,18例因不能耐受体位性低血压症状而完成部分试验,3例完成全部试验。统计表明,无症状组平卧位与斜立位的血压差异有非常显著性意义,平卧位与斜立30°的脉搏、CBF速度差异无显著性意义,与斜立60°、80°差异有显著性意义。有症状组平卧位与斜立30°的CBF差异无显著性意义,斜立各角度间的CBF差异有显著性意义。两组在斜立30°时收缩压差异有显著性,而脉搏、CBF速度差异无显著性意义。结论:①脊髓损伤后早期,斜立30°15min不影响CBF速度,不出现OH症状;②血压下降并不是引起OH出现症状的直接原因,CBF速度下降是引起OH症状的直接原因。

脊髓缺血再灌流对其血流量变化及其病理改变关系的研究

目的：研究缺血再灌流损伤脊髓血流量的变化及其与脊髓病理改变间的关系。方法：20只成年日本大耳白家兔随机分为对照组、缺血30min组、缺血60min组和缺血90min组，用氢清除法测定脊髓血流量（SCBF），尼氏染色观察受损脊髓病理变化。结果：完全缺血时SCBF为0ml·100g-1·min-1，再灌流过程中各组SCBF较缺血时有不同程度的恢复，但较伤前仍有不同程度的下降，并以缺血60min、90min组下降明显；脊髓病理改变以灰质受损最明显，病变严重程度为缺血90min组＞缺血60min组＞缺血30min组＞对照组。结论；缺血时间越长，再灌流后SCBF下降越明显，病理损害也越重。

三七总皂甙对脊髓损伤后脊髓血流量和感觉诱发电位的影响

目的 探讨脊髓损伤后三七总皂甙 (totalsaponinsofpanaxnotoginseseng ,PNS)对脊髓血流量及神经功能的影响。方法 Wistar大鼠 2 0只 ,随机分为生理盐水对照组 (NS组 )和PNS治疗组 (PNS组 )。Allen’s打击法 5 0gcm ( 5g× 10cm)致伤大鼠L1 L2 段脊髓 ,立即腹腔注射PNS(生理盐水配制 ,10ml kg ,2 0mmol L) ,于伤前、伤后即刻、1、3、6、2 4h分别记录T13段脊髓血流量、脊髓感觉诱发电位。结果 与盐水对照组比较 ,应用PNS后 ,大鼠SCBF、SEP明显优于生理盐水对照组 (P <0 0 5 )。结论 大剂量PNS能有效改善损伤早期脊髓微循环 。

2-氯腺苷对大鼠脊髓损伤后脊髓血流量和神经功能的影响

目的 :观察腺苷受体激动剂 2 -氯腺苷对大鼠脊髓损伤后神经功能和脊髓血流量的影响 ,探讨腺苷在继发性脊髓损伤中的作用。 方法 :脊髓腹侧压迫法造成 T1 3 脊髓损伤 ,用激光多普勒血流仪检测损伤前后的脊髓血流量 ,治疗组于伤前 15min蛛网膜下腔注射不同剂量的非特异性腺苷受体激动剂 2 -氯腺苷 (2 - CADO) ,对照组注射同量的生理盐水。伤后 2 4h观察神经功能评分、倾斜平面临界角和组织学变化。 结果 :脊髓损伤后脊髓血流量立即下降 ,而治疗组较对照组显著改善 (P<0 .0 5 ,P<0 .0 1)。大剂量 (5 0 0μmol/ L )的 2 - CADO能显著改善损伤后的神经功能 ,而小剂量 (5 0μmol/ L )则对脊髓损伤无明显神经保护作用 ,大小剂量的作用有显著差异 (P<0 .0 1)。 结论 :腺苷通过改善脊髓血流量 ,从而对脊髓损伤起保护作用。

强啡肽A及其受体拮抗剂对大鼠脊髓损伤后脊髓血流量的影响

目的：探讨强啡肽Ａ在脊髓损伤（ＳＣＩ）中的作用。方法：采用Ａｌｌｅｎ打击法复制大鼠ＳＣＩ模型，应用强啡肽Ａ放免检测技术和氢清除法分别测定伤段脊髓组织２４ｈ内强啡肽Ａ含量和脊髓血流量（ＳＣＢＦ）的变化，并观察脊髓蛛网膜下腔注射强啡肽Ａ及其受体拮抗剂ｎｏｒ－ＢＮＩ对ＳＣＢＦ的影响。结果：ＳＣＢＦ在伤后１０ｍｉｎ即有明显下降、２ｂ较１ｈ略有回升，４～８ｈ又进一步下降，两次下降相差显著；ＳＣＩ后脊髓蛛网膜下腔注射强啡肽Ａ可明显加剧脊髓缺血，而注射强啡肽受体拮抗剂ｎｏｒ－ＢＮＩ则可显著减轻脊髓缺血。脊髓强啡肽Ａ含量在伤后１０ｍｉｎ明显升高，１～２ｈ有所下降，但仍高于对照组，４，８ｈ较２ｈ略增加。强啡肽Ａ含量与ＳＣＢＦ的变化，两者呈显著相关性。结论：ＳＣＩ后强啡肽Ａ的过度释放是ＳＣＩ后继发性损伤的重要因素。

颈髓损伤患者循环系统动态变化的临床研究

目的 探讨颈髓损伤 (ＣＳＣＩ)后循环系统的动态变化。方法 回顾性对比分析了 47例ＣＳＩ患者与 57例非ＣＳＣＩ患者血压、心率、心电图的动态变化以及ＣＳＣＩ平面、颈髓反射复前后对血压、心率、心电图的影响。结果 ＣＳＣＩ患者血压、心率明显降低 (Ｐ < 0 . 0 1 );颈4以上比颈 4以下损伤患者的血压、心率下降更为明显 (Ｐ < 0 . 0 5);心电图除出现窦性心动过缓改变外 ,同时还出现ＳＴ段下移、Ｔ波低平 ,Ｕ波、ＱＲＳ波、Ｑ -Ｔ间期时限延长等心电异常表现 (Ｐ < 0 . 0 1 )。颈髓反射恢复后血压、心率明显升高 (Ｐ <0 . 0 1 ),心电图恢复正常 (Ｐ< 0 . 0 1 )。结论 ＣＳＣＩ后循环系统功能有明显异常改变 ,主要发生在脊髓休克期 ,且损伤平面越高 。

动脉阻断致颈髓急性缺血性损伤的实验研究

[目的]研究颈髓脊髓前动脉、前根动脉阻断对颈髓缺血性损伤的影响。[方法]将48只家兔随机分为阻断脊髓前动脉组和间接阻断前根动脉组(阻断脊髓前动脉+双侧椎动脉),两组均设有对照组。每组各在术后6、24、72 h检测颈髓血流灌注量,运动诱发电位、组织能量代谢变化,电镜观察细胞形态学改变。[结果]脊髓前动脉阻断后颈髓前部表面血流量下降了50.28%,随后有所回升;运动诱发电位潜伏期延长;ATP和EC进行性下降,出现急性缺血性改变;间接阻断前根动脉组其各指标变化更加明显,同阻断脊髓前动脉相比,存在显著差异,P<0.05。[结论]脊髓前动脉对颈髓前部血流起着重要的作用,阻断后造成脊髓缺血性损伤,但有部分代偿;前根动脉对颈髓血供有重要的补充和支持作用,临床上各种原因造成的根动脉损伤势必对颈髓带来损害。

血小板活化因子对颈髓损伤后血脊髓屏障的影响

目的：探讨血小板活化因子（Ｐｌａｔｅｌｅｔａｃｔｉｖａｔｉｎｇｆａｃｔｏｒ，ＰＡＦ）对颈髓损伤后血脊髓屏障的影响。方法：采用蛛网膜下腔注射ＰＡＦ及静脉注射ＰＡＦ受体拮抗剂ＢＮ５２０２１，观察其对颈髓损伤后伤区及邻近脊髓组织ＰＡＦ含量、血脊髓屏障、颈髓水肿的影响。结果：颈髓损伤后颈髓伤区及邻近脊髓组织ＰＡＦ含量、伊文思蓝含量、水含量均明显增加，蛛网膜下腔注射ＰＡＦ可使伤后ＰＡＦ含量、伊文思蓝含量、水含量增加更为显著。ＰＡＦ受体拮抗剂ＢＮ５２０２１可抑制伤后颈髓组织ＰＡＦ含量升高，降低颈髓组织伊文思蓝含量及水含量。结论：ＰＡＦ是导致颈髓损伤后血脊髓屏障损害的重要因素之一，而ＰＡＦ受体拮抗剂可有效减轻伤后血脊髓屏障的损害。

外加电场对实验性大鼠脊髓损伤作用的研究

目的:探讨脊髓损伤后外加电场(electric fields,EF)对脊髓血流量(spinal cord blod flow,SCBF)及神经功能的影响。方法:Wistar大鼠20只,随机分为对照组(CON组)和EF治疗组(EF组)。Allen's打击法50 gcm(5 g×10 m)致伤大鼠L1～L2段脊髓,给予EF治疗,于伤前、伤后即刻、1、3、6、24 h分别记录T12段脊髓血流量、脊髓感觉诱发电位。术后7、14天行联合行为评分(CBS)。结果:与盐水对照组比较,应用EF后,大鼠SCBF、SEP明显优于CON组(P<0.05)。结论:EF能有效改善损伤早期脊髓微循环,保护脊髓神经功能。

急性脊髓前动脉及双侧椎动脉阻断对颈髓血流量影响的实验研究

目的:研究颈部脊髓前动脉及双侧椎动脉阻断对颈髓血流量的影响及其病理学变化。方法:将48只家兔随机分为阻断脊髓前动脉组与阻断脊髓前动脉和双侧椎动脉组,术后6h、24h、72h采用激光多普勒血流测定仪检测颈髓血流灌注量,电镜观察颈髓组织细胞形态学、免疫组化检测神经丝的变化。结果:脊髓前动脉阻断后颈髓血流量下降1/2,随后有所回升,但依然处于低灌注状态;阻断脊髓前动脉和双侧椎动脉后,其血流量下降更为显著,为对照组的1/3,电镜及免疫组化显示两组均出现了缺血性改变,经统计学检验两组每一时相点的血流量和神经丝表达程度均有显著性差异(P<0.05)。结论:颈髓前部血流量除与脊髓前动脉有关外,前根动脉也有一定的作用,临床上各种原因造成脊髓前动脉或根动脉的损伤均可能导致颈髓缺血性损伤。