Correlation of Pathological Findings with MRI Imaging in Traumatic Spinal Cord Injury in Hyperacute Time Period in Non Human Primate Model

Traumatic Spinal Cord Injury (TSCI) remains a significant cause of human suffering. The World Health Organization estimates that there are between 250,000 to 500,000 new cases every year. Magnetic Resonance Imaging (MRI) has been an important advancement in the diagnosis and management of TSCI. Nevertheless, there is a lack of literature correlating the radiological abnormalities and histopathological findings in the first hour (i.e., hyperacute period) after injury. The aim of this preliminary study is to elucidate the relationship between the MRI abnormalities and histopathological abnormalities in the hyperacute time period. In this study, a non-human primate model (NHP) primate model is used to characterize the histopathological and radiological features. Specifically, an experimental TSCI is created with an epidural catheter. This is followed by MRI imaging. The subject is then humanely euthanized and a post-mortem examination is completed. These results suggest that the noted radiological abnormalities are consistent with a combination of hemorrhage, edema as well as eosinophilic cellular matter in the central canal.

Protective effect of thodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury

Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein expression was greater in the rhodioloside group(P<0.05).(3)Compared with the Ad-HIF-MSC group,Sry mRNA levels were higher in the rhodioloside+Ad-HIF-MSC group(P<0.05).These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue.This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine,China(approval No.2015KYLL029)in June 2015.

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.

Effects of decompression joint Governor Vessel electro-acupuncture on rats with acute upper cervical spinal cord injury

Decompression is the major therapeutic strategy for acute spinal cord injury,but there is some debate about the time window for decompression following spinal cord injury.An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury.Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord.In this study,Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury.The rat models were established by inserting a balloon catheter into the atlanto-occipital space.The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression.Electroacupuncture was conducted at the acupoints Dazhui（GV14） and Baihui（GV 20）（2 Hz,15 minutes） once a day for 14 consecutive days.Compared with decompression alone,hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture.However,the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours.Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone.These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression（48 hours） is more effective in the treatment of upper cervical spinal cord injury.Governor Vessel electroacupuncture combined with early decompression（12 hours） can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury.Nevertheless,further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.

Management of acute spinal cord injury:A summary of the evidence pertaining to the acute management,operative and non-operative management

Acute traumatic spinal cord injury is often a lifechanging and devastating event with considerable mortality and morbidity.Over half a million people suffer from traumatic spinal cord injury annually with the majority resulting from road traffic accidents or falls.The Individual,societal and economic costs are enormous.Initial recognition and treatment of acute traumatic spinal cord injury are crucial to limit secondary injury to the spinal cord and to provide patients with the best chance of some functional recovery.This article is an overview of the management of the acute traumatic spinal cord injury patient presenting to the emergency department.We review the initial assessment,criteria for imaging and clearing the spine,and evaluate the literature to determine the optimum timing of surgery and the role of non-surgical treatment in patients presenting with acute spinal cord injury.

Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury

All synthetic and natural estrogen receptor agonists, in- cluding the most potent physiological molecule estrogen or estradiol （E2）, work typically via activation of nuclear estrogen receptor alpha （ERα） and estrogen receptor beta （ERβ）. Both ERα and ERβ modulate the expression of a variety of genes in the cells. Neurons and glial cells express ERa and ERβ. Many studies so far from our and other laboratories have firmly established the mode of actions that ERα and ERβ agonists are very promising anti-inflammatory and neuroprotective agents in the treatment of neurodegenera- rive diseases and injuries including spinal cord injury （SCI） （Chakrabarti et al., 2014a）.

Early methylprednisolone impact treatment for sensory and motor function recovery in patients with acute spinal cord injury A self-control study

BACKGROUND： For the treatment of spinal cord injury, any pathological changes of the injured tissue should be primarily corrected or reversed. Any remaining fibrous function and neurons with intact structure should be retained, and the toxic substances caused by ischemia-hypoxia following spinal cord injury, should be eliminated to create a favorable environment that would promote neural functional recovery. OBJECTIVE： This study was designed to investigate the effects of the impact of early methylprednisolone-treatment on the sensory and motor function recovery in patients with acute spinal cord injury. DESIGN： A self-control observation. SETTING： Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. PARTICIPANTS： Forty-three patients with acute spinal cord injury were admitted to the Department of Spine Surgery, First Affiliated Hospital of Nanjing Medical University, between October 2005 and September 2007. These patients were recruited for the present study. The patients comprised 33 males and 10 females, and all met with the inclusive criteria namely, the time between suffering from acute spinal cord injury and receiving treatment was less than or equal to eight hours. METHODS： According to the protocol determined by the State Second Conference of Acute Spinal Cord Injury of USA, all patients received the drop-wise administration of a 30-mg/kg dose of methylprednisolone （H200040339, 500 mg/bottle, Pharmacia N.V/S.A, Belgium） for 15 minutes within 8 hours post injury. After a 45-minute interval, methylprednisolone was administered at 5.4 mg/kg/h for 23 hours. MAIN OUTCOME MEASURES： Prior to and post treatment, acupuncture sense and light touch scoring were performed at 28 dermatomic area key points, including occipital tuberosity and supraclavicular fossa. At the same time, motor scoring of key muscles among 10 pairs of sarcomeres was also performed. RESULTS： All 43 patients participated in the final analysis. There was no significant difference of sensory and motor scores in patients with complete acute spinal cord injury between prior to and post methylprednisolone impact treatment （P 〉 0.05）. The motor score was significantly decreased in patients with incomplete acute spinal cord injury post methylprednisolone impact treatment （P 〈 0.01 ）. CONCLUSION： Early methylprednisolone impact may improve the motor function of patients with incomplete acute spinal cord injury. However, it has no influences on patients with complete acute spinal cord injury.

Provision of nutrients after acute spinal cord injury: the implications of feast and famine

Traumatic spinal cord injury（SCI）often leaves patients with devastating neurological deficits.The traumatic event–or primary injury–can be due to mechanisms such as compression,distraction,shear,laceration or（rarely）even transection.Thereafter SCI patients are vulnerable to progressive,delayed damage as a result of secondary insults and secondary injury.Secondary insults such as hypoxia and hypotension occur at the level of the organism from a myriad of causes.

Effect of electroacupuncture at Jiaji (EX-B2) points on the expression of microRNA-21 and neuronal apoptosis in rats with acute spinal cord injury

Objective:To observe the effect of electroacupuncture at Jiaji (EX-B2) points on the expression of microRNA-21 and neuronal apoptosis in rats with acute spinal cord injury. Methods:SD rats were randomly divided into sham-operated group, model group, electro-acupuncture group and methylprednisolone group. The model of acute spinal cord injury was reproduced by modified Allen's method. Each group was given corresponding intervention treatment 2 hours after modeling. The electroacupuncture group was treated with electro-acupuncture at Jiaji (EX-B2) points in T8 to T12, the methylprednisolone group was given intraperitoneal injection of 30 mg/kg methylprednisolone sodium succinate, and the sham operation group and model group were not treated. After treatment, BBB scores were observed to evaluate the motor function of posterior limb in each group, and the injured spinal cord tissues were taken. The pathological changes of spinal cord neuropathy were observed by Nissl staining. The expression of microRNA-21 was detected by RT-qPCR, and the expression of apoptotic proteins (Bax, Bcl-2 and cleaved-Caspase-3) was detected by Western-Blot. Result:Compared with sham operation group, BBB, neuron survival rate and expression of microRNA-21 were significantly lower, apoptotic rate of neurons was significantly higher, expression of Bax, Bcl-2, cleaved Caspase-3 protein and Bax/Bcl-2 ratio were significantly increased in model group (P< 0.05). Electroacupuncture could significantly increase BBB score, neuron survival rate and expression of microRNA-21, reduce apoptotic rate of neurons and the ratio of Bax/Bcl-2, and inhibit the expression of Bax, Bcl-2 and cleaved Caspase-3 protein in tissues, which were significantly different from those of model group (P< 0.05). Conclusions: Electroacupuncture at Jiaji (EX-B2) points can significantly promote the recovery of neurological function in rats after ASCI, and its mechanism may be closely related to the up-regulation of the expression of microRNA-21 in tissues and the inhibition of the activation of Bax/Bcl-2/cleaved Caspase-3 signaling pathway.

Effect of FTY720 on RhoA expression after acute spinal cord injury in rats

Objective To investigate the effect of fingolimod (FTY720)on RhoA expression after spinal cord injury (SCI)in rats,and explore the possible mechanism of FTY720in the treatment of SCI.Methods A rat model of acute SCI was established with a

Effects of low dose Glibenclamide on secondary damage after acute spinal cord injury in rats

Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated

Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 μg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, casp ase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.

Current therapeutic strategies for inflammation following traumatic spinal cord injury

Damage from spinal cord injury occurs in two phases-the trauma of the initial mechanical insult and a secondary injury to nervous tissue spared by the primary insult.Apart from damage sustained as a result of direct trauma to the spinal cord,the post-traumatic inflammatory response contributes significantly to functional motor deficits exacerbated by the secondary injury.Attenuating the detrimental aspects of the inflammatory response is a promising strategy to potentially ameliorate the secondary injury,and promote significant functional recovery.This review details how the inflammatory component of secondary injury to the spinal cord can be treated currently and in the foreseeable future.

Electrical stimulation and denervated muscles after spinal cord injury

Spinal cord injury(SCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous tissue.These morphological changes may put individuals with SCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and osteoporosis.Currently,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in SCI individuals with lower motor neuron denervation.We,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following SCI.Long pulse width stimulation(LPWS)technique is an upcoming method of stimulating denervated muscles.Our primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated muscle.Stimulation parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and contraction.The use of electrical stimulation in animal and human models induces muscle hypertrophy.Findings in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle function.Human studies have shown similar outcomes,identifying the use of LPWS as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle function.Therefore,displaying promise is an effective future stimulation intervention.In summary,LPWS is a novel stimulation technique for denervated muscles in humans with SCI.Successful studies on LPWS of denervated muscles will help in translating this stimulation technique to the clinical level as a rehabilitation intervention after SCI.

MRI and EM Observation of Repair Effect of Implantation of Microgene pSVPoMcat Modified SC on Injured Spinal Cord

Objective To approach the effect of microgene pSVPoMcat modified Schwan n cell (SC) on the regeneration and repair of injured spinal cord.Method Spinal cord hemi－transection models were made with the cutting method in healthy SD ra ts. Microgene pSVPoMcat modified SC(group A),highly purified SC(group B),and glu tin sponge (control group C)were randomly implanted into the cut. After 3 month living ,the host rats were scanned by MRI, and observed under EM. Result Spinal signals at the injury region nearly recovered to normal in group A.No recovery w as found in group B.Malacosis was found in group C.TEM findings: regeneration of large number of myelinated and nonmyelinated axons and SC proliferation in grou p A, myelinated axon regeneration and SC necrosis in group B, non myelinated and nonmyelinated axon in group C.Conclusion Implantation of microgene pSVPoMcat mo dified SC could promote the repair of injured spinal cord.

Identification of potential oxidative stress biomarkers for spinal cord injury in erythrocytes using mass spectrometry

Oxidative stress is a hallmark of secondary injury associated with spinal cord injury.Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury.Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated.Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker.In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches.We found 26 proteins that were differentially expressed in the acute(0–3 days) and subacute(7–21 days) phases of spinal cord injury.Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways.Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase.This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury.Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury.This study was approved by the Experimental Animal Centre of Ningxia Medical University, China(approval No.2017-073) on February 13, 2017.

常规MRI在创伤性脊髓损伤预后评估中的研究进展

创伤性脊髓损伤(TSCI)常由直接的机械性损伤引起,是一种严重的致残性疾病。临床上常借助常规脊髓MRI对脊髓损伤(SCI)严重程度进行评估,所以探讨常规MRI在TSCI中的全面应用进展是非常必要的。MRI可显示TSCI不同时期的变化,急性期MRI能显示脊髓水肿和出血范围,在亚急性期,随着水肿和出血的消退,MRI指标可能对损伤严重程度诊断和预后预测有更大价值;而慢性期MRI能够观察TSCI后脊髓和脑内的萎缩情况。本文回顾近几年相关文献,对TSCI在MRI上的信号表现及MRI对评估神经功能缺损和预测恢复的价值进行阐述,以期为TSCI患者的诊疗和康复及未来研究方向提供建议。

急性颈髓损伤^1H—MRS与MRI的对照研究

目的 对照研究磁共振质谱 (1H -MRS)与MRI对急性颈髓损伤的诊断价值。方法 根据 19例急性颈髓损伤患者的MRI表现 ,分为脊髓正常信号组 (损伤组Ⅰ )和脊髓异常信号组 (损伤组Ⅱ ) ,并以 9例健康者作对照。进行1H -MRS检查 ,并计算氮 -乙酰天门冬氨酸 (NAA)、胆碱 (Cho)、肌酸 (Cr)、乳酸 (Lac)波峰面积 ,分析NAA/Cho、NAA/Cr、Cr/Cho、Lac/Cho。结果 损伤组Ⅰ与对照组比 ,仅Lac/Cho值升高 (P <0 .0 5 )。损伤组Ⅱ与对照组比 ,NAA/Cho、NAA/Cr值降低 ,Lac/Cho值升高 (P <0 .0 1)。损伤组Ⅱ较损伤组ⅠNAA/Cho、NAA/Cr显著减低 (P <0 .0 5 )。结论 1H -MRS可定量测定创区颈髓相关代谢介质的变化 ,从代谢水平反映颈髓损伤的不同程度。MRI结合1H -MRS更有利于颈髓损伤评价。

Guidelines for management of pediatric acute hyperextension spinal cord injury

Pediatric acute hyperextension spinal cord injury(SCI)named as PAHSCI by us,is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training,which has been increasingly reported.At present,it has become the leading cause of SCI in children,and brings a heavy social and economic burden.Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards,specifications or guidelines.In order to provide standardized guidance,the expert team formulated this guideline based on the principles of science and practicability,starting from the diagnosis,differential diagnosis,etiology,admission evaluation,treatment,complications and prevention.This guideline puts forward 23 recommendations for 14 related issues.

Spinal Cord Injuries without Visible Bone Lesions: Analysis of Four Consecutive Cases

Objectives: Interest of this study is to report four cases of spinal cord injuries without bone lesion. Evolution of the injured patients according to the initial clinic assessment at admission and the treatment performed are discussed. Materials and Methods: From January to December 2016, we performed a retrospective study at the Neurosurgery Department of Hospital General Grand Yoff of Dakar. Four patients were followed for spinal cord injury without visible bone lesions. We analyzed the clinical, radiological, therapeutic and evolutionary data. Trauma caused by stabbing was excluded. Results: In a year, 83 cases of spinal trauma with neurological deficit were hospitalized in the department. Among them, 4 had spinal cord injuries without visible bone lesions. The average age was 31.7 years with extremes ranging from 14 to 47 years. The sex ratio of male/female was 3. We have recorded 2 cases of road traffic accidents, 1 case of fall from height and 1 case of sports accident. On the neurological level, we found 3 cases of tetraplegia, and 1 brachial monoplegia. Computed tomography in all patients was normal. All of them benefited from magnetic resonance imaging that showed spinal cord injury. All patients were under conservative treatment. One patient fully recovered, two partially and one passed away. Conclusion: In presence of any post traumatic myelopathy case, the absence of disco-vertebral lesions should bring to mind the SCIWORA as well as indicate the realization of magnetic resonance imaging.