Neural prostheses for restoring functions lost after spinal cord injury

Spinal cord injury（SCI）is a debilitating condition that affects more than 2.5 million individuals worldwide（Thuret et al.,2006）.In addition to its devastating effects on the individual,this disease is a heavy burden to the society in terms of health care costs, which are estimated in billions of dollars annually in most developed countries （Cadotte and Fehlings, 2011）.

Reorganization of spinal neural circuitry and functional recovery after spinal cord injury

The ability of the adult central nervous system to reorganize its circuits over time is the key to understand the functional improvement in subjects with spinal cord injury （SCI）. Adaptive changes within spared neuronal circuits may occur at cortical, brainstem, or spinal cord level, both above and below a spinal lesion （Bareyre et al., 2004）. At each level the reorganization is a very dynamic process, and its degree is highly variable, depending on several factors, including the age of the subject when SCI has occurred and the rehabilitative therapy. The use of electrophysiological techniques to assess these functional changes in neural networks is of great interest, because invasive methodologies as employed in preclinical models can obviously not be used in clinical studies.

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.

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.

Functional changes after spinal lesions: implications for interventions

We have known for many years that the spinal cord can generate some basic locomotor outputs under specific experimental conditions without any input from the brain or the periphery（Stuart and Hultborn,2008）.However,when inputs from the brain are lost following spinal cord injury（SCI）,the mammalian spinal cord is unable to generate normal,goal-directed locomotor outputs.

Extrinsic inhibitors in axon sprouting and functional recovery after spinal cord injury

The limited axonal growth after central nervous system （CNS） injury such as spinal cord injury presents a major challenge in promoting repair and recovery. The literature in axonal repair has focused mostly on frank regeneration of injured axons. Here, we argue that sprouting of uninjured axons, an innate repair mech- anism of the CNS, might be more amenable to modulation in order to promote functional repair. Extrinsic inhibitors of axonal growth modulate axon sprouting after injury and may serve as the first group of therapeutic targets to promote functional repair.

Senegenin inhibits neuronal apoptosis after spinal cord contusion injury

Senegenin has been shown to inhibit neuronal apoptosis,thereby exerting a neuroprotective effect.In the present study,we established a rat model of spinal cord contusion injury using the modified Allen＇s method.Three hours after injury,senegenin（30 mg/g） was injected into the tail vein for 3 consecutive days.Senegenin reduced the size of syringomyelic cavities,and it substantially reduced the number of apoptotic cells in the spinal cord.At the site of injury,Bax and Caspase-3 m RNA and protein levels were decreased by senegenin,while Bcl-2 m RNA and protein levels were increased.Nerve fiber density was increased in the spinal cord proximal to the brain,and hindlimb motor function and electrophysiological properties of rat hindlimb were improved.Taken together,our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury.

Promoting functional recovery by inhibition of repulsive guidance molecule-a after spinal cord injury

Spinal cord injury（SCI）leads to permanent disability with motor and sensory dysfunctions.The mature mammalian central nervous system（CNS）possesses a limited capacity to regenerate/regrow after injury.

Propriospinal interneurons in the spotlight for anatomical and functional recovery after spinal cord injury

Spinal cord injury（SCI）with consecutive paralysis below the lesion level is a severe disorder affecting the patient for the rest of his or her life.So far,there is no known fundamental intervention strategy for efficiently helping those patients regain their motor abilities,despite intense research in this area.Thus,effective treatment for those patients is still an open question. A spinal cord injury is accompanied by a prima- ry, severe and irreversible neuronal cell death in the trauma region, fol- lowed by a secondary extensive cell necrosis in the lesion surrounding areas. Nevertheless, recent studies indicate that regeneration after spinal cord injury could be possible if three substantial steps are fulfilled： （1） reduction of the inhibitory environment at the SCI lesion site, （2） iden- tification of a neural substrate to establish new spinal circuits, and （3） support of these circuits to form permanent, functional motor, sensory, or autonomic connections （Dru and Hoh, 2015）.

Anatomical changes in the somatosensory system after large sensory loss predict strategies to promote functional recovery after spinal cord injury

Among cases of spinal cord injury are injuries involving the dorsal column in the cervical spinal cord that interrupt the major cutaneous afferents from the hand to the cuneate nucleus（Cu）in the brainstem.Deprivation of touch and proprioceptive inputs consequently impair skilled hand use.

Functional evaluation using several evoked spinal cord potentials in elderly patients with cervical spondylotic myelopathy

BACKGROUND ： The recordings of evoked spinal cord potentials following epidural spinal cord stimulation are thought to be generated by volleys traversing the dorsal column pathway, and it may not directly reflect conduction defects in corticospinat tracts of cervical spinal cord. To our knowledge there has been few report using several evoked spinal cord potentials in function evaluation of the cervical spinal cord in eldedy patients with cervical spondylotic myelopathy （CSM）. OBJECTIVE： To investigate the function states of the cervical spinal cord in elderly patients with CSM and explore its pathophysictogic mechanism. DESIGN： Case observation SETTING ： Department of Orthopedics for the aged, Shenzhen Pingle Hospital of Orthopedics. Department of Orthopedic Surgery, Yamaguchi University School of Medicine. PARTICIPANTS ： A total of 23 eldedy patients with CSM who received treatment in the Department of Orthopedic Surgery, Yamaguchi University School of Medicine of Japan from January 2003 to February 2004 were enrolled in this study. Inclusive criteria： ① Multiple intervertebral levels of cervical spinal cord compression confirmed by MRI, e.g. 3 or more than 3 levels of compressin. ② Age ≥ 70 years old. ③ Numbness and sensory disturbance in the upper limbs and showed hyperreflexia in the lower limbs. Exclusive criteria： Patients with abnormal motor and sensory nerve conduction velocities in both upper and lower limbs were excluded. METHODS： Evoked spinal cord potentials （ESCPs） following transcranial electric stimulation （TCE-ESCPs）, epidural spinal cord stimulation （SpinaI-ESCPs） and median nerve stimulation （MN-ESCPs） were recorded in 23 patients from posterior epidural space intreoperatively. The abnormalities of TCE-ESCPs were defined as attenuation of amplitude of the D wave. The most cranial intervertebral level showing abnormal TCE-ESCPs with a marked reduction in size of the negative peak （reduction of over 50%） was considered as the upper level of the spinal cord lesion with respect to the corticospinal tract in white matter. The abnormalities of SpinaI-ESCPs were defined as marked reduction in the size of negative peak （reduction of over 50%）. The most caudal intervertebral level showing abnormal SpinaI-ESCPs was considered as the lower level of the spinal cord lesion with respect to the dorsal column pathway in white matter. The abnormalities of MN-ESCPs were defined as attenuation of the N13 amplitude,which was considered as the lesion level of the spinal cord with respect to the dorsal horn in gray matter. Radiological investigation： Lateral view of plain X-ray films was obtained in flexion and extension of the cervical spine. Instability of the cervical intervertebral level was determined as horizontal displacement of the vertebral body of over 3 mm. MAIN OUTCOME MEASURES ： The results of examination of TCE-ESCPs, SpinaI-ESCPs and MN-ESCPs in el- dedy patients with CSM. RESULTS： The 23 eldedy patients with CSM were participated in the result analysis. ①TCE-ESCPs： The impairment of the corticospinal tract in white matter at single intervertebral level was revealed in 18 of 23 patients by recordings of TCE-ESCPs （sensitivity 78%）. In the 18 patients, the lesion level was shown at the up- per cervical segment in 14 patients （C3-4n=10 and C4-5n=4）, and at the lower cervical segment in 4 patients （C5-6n=4）. ②Spinal-ESCPs： The impairment of the dorsal column pathway of white matter at single intervertebral level was revealed in 17 of 23 patients, by recordings of Spinal-ESCPs （sensitivity 74%）. In the 17 patients, the lesion level was presented at the upper cervical segment in 14 patients （C3-4n=10 and C4-5n=4）, and at the lower cervical segment in 3 patients （C5-6 n=3）. ③MN-ESCPs： All patients revealed abnormal MN-ESCPs at one or more intervertebral levels （sensitivity 100%）. The impairment at single intervertebral level was demonstrated in 17 patients, and the impairment at multiple intervertebral levels was shown in 4 patients （3 patients at the C3-4, C4-4, and C5-4~6, and one patient at the C4-5, C5-6, and C6-7）. ④Radiological findings： The Instability of the intervertebral level at the C3-4 or C4-5 motion segment was seen in 15 patients, with a total of 20 levels, and where 10 were at the C3-4 intervertebral level and 5 were at the C3-4, C4-5 intervertebral level. CONCLUSION ： The results suggest that in most elderly patients with CSM who have multiple intervertebral level compressions of the cervical spinal cord on MRI, white matter is impaired at the single cervical intervertebral level, and not only the dorsal column pathway, but also the corticospinal tract can be affected. Combined the findings of radiography, the excessive motion and instability of the C3-4 or C4-5 intervertebral level plays an important role in inducing the long tract lesion in elderly patients with CSM.

Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells

Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to

Experimental Study on Stress Relaxation and Creep Properties of Human Thoracolumbar Vertebral Bodies and Intervertebral Discs

Objective:Underwater shock can produce extremely high accelerations, resulting in severe human injuries on shipboard, and human thoraco lumbar spines are prone to suffer from injuries by ship shock motion. To observe the viscoelasticity of thoracolumbar of young fresh cadavers, and to provide biomechanical parameters for both research and clinical practice. Materials and Methods:5 fresh young male cadavers (aged 22 to 31 years) were provided, and 15 thoracolumbar spinal anatomies of 5 samples were harvested within 1 hour of death. WE-10A universal testing machine was used for creep and relaxation tests.Results:Stress relaxation and creep deformation equations are derived from the biomechanics model and the measured and simulated curves are compared. The creep in vertebral bodies and intervertebral discs exhibited significantly changes in the first 5 min and 10 min, respectively. The stress rapidly decreased in the first 2 min, and then gradually went balance during the relaxation process. Conclusion:The change in creep rate is significant at early stage,and gradually slows down.This indicates that the differences between internal pressure and local pressure are decreased until balance. The simulated curve derived from equation coincides with the experimental data to a large degree, which states that the equation is rational and reliable.

Influence of patients' age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury

Objective To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells (OECs). Methods One hundred and seventy-one SCI patients were included in this study. Of them,139 were male and 32 were female,with age ranging from 2 to 64 years (mean,34.9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages,the patients were divided into 5 groups: ≤20 years group (n=9),21-30 years group (n=54),31-40 years group (n=60),41-50 years group (n=34) and>51 years group (n=14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2-8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis,and the data were expressed as mean±SD. Results After surgery,the motor scores increased by 5.2±4.8,8.6±8.0,8.3±8.8,5.7±7.3 and 8.2±7.6 in 5 age groups respectively ( F =1.009,P =0.404); light touch scores increased by 13.9±8.1,15.5±14.3,12.0±14.4,14.1±18.5 and 24.8±25.3 respectively ( F =1.837,P =0.124); and pin prick scores increased by 11.1±7.9,17.2±14.3,13.2±11.8,13.6±13.9 and 25.4±24.3 respectively ( F =2.651,P =0.035). Restoration of pin prick in >51 years group was better than other age groups except 21-30 years group. Conclusion OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.

A Clinical Observation of Functional Abdominal Pain Syndrome in Patients Treated by Traditional Chinese Spinal Orthopedic Manipulation

Objective： To evaluate the clinical effect of traditional Chinese spinal orthopedic manipulation（TCSOM） in treating patients with functional abdominal pain syndrome（FAPS） in comparison with Pinaverium Bromide（Dicetel, PBD）, and to assess a possible cause for FAPS. Methods： Eighty patients with FAPS were randomly and equally assigned to the TCSOM group and PBD group according to the random number table. All patients in the TCSOM group were treated with a maximum of 5 times of spinal manipulations. Patients in the PBD group were instructed to take 50 mg 3 times a day, consistently for 2 weeks. The symptoms of pre-and post-treatment were assessed on a visual analog scale（VAS） pain score. A symptom improvement rating（SIR） was implemented to evaluate the effects of the treatments. Results： The symptoms of 27 cases of the TCSOM group were relieved soon after the first TCSOM treatment and 9 cases were significantly improved. The VAS pain scores in the TCSOM group were significantly lower than those in the PBD group after 2 weeks treatment. According to the SIR based on VAS, the TCSOM group included 30 cases with excellent results, 7 cases with good, and 3 cases with poor. Adverse events to the treatment were not reported. Based on VAS, the PBD group reported 8 cases with excellent results, 10 cases with good and 22 cases with poor. There was a significant difference between the two groups（P〈0.01）. Conclusions： The displacement of intervertebral discs and/or vertebra in the thoracic or lumbar region seems to be a contributing factor in the symptoms of FAPS. TCSOM is an effective treatment for FAPS.

Removal versus preservation of the posterior longitudinal ligament in Bryan cervical disc arthroplasty

Background Bryan cervical disc arthroplasty can be used to restore and maintain the mobility and function of the involved cervical spinal segments. The efficiency of posterior longitudinal ligament （PLL） resection in anterior cervical decompression and fusion has been demonstrated. However, no clinical reports have compared PLL removal with preservation in Bryan cervical disc arthroplasty. This study aimed to assess the role of removal of PLL in Bryan cervical disc arthroplasty at an 18-month follow-up.