Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury:a cross-sectional pilot study

Skeletal muscle stiffness is altered after spinal cord injury(SCI).Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after SCI.The study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size,spasticity,and peak torque in persons with SCI.Previous studies examined the association between muscle stiffness and spasticity,however,we are unaware of other studies that examined the effects of muscle composition on stiffness after SCI.Ten participants(one female)with chronic SCI and eight(one female)matched able-bodied controls participated in this cross-sectional study.Magnetic resonance elastography was utilized to monitor stiffness derived from shear waves propagation.Modified Ashworth scale was used to evaluate spasticity scores in a blinded fashion.Peak isometric and isokinetic torques were measured using a biodex dynamometer.Stiffness values were non-significantly lower(12.5%;P=0.3)in the SCI group compared to able-bodied controls.Moreover,stiffness was positively related to vastus lateralis whole muscle cross-sectional area(CSA)(r2=0.64,P<0.005)and vastus lateralis absolute muscle CSA after accounting for intramuscular fat(r2=0.78,P<0.0007).Stiffness was also positively correlated to both isometric(r2=0.55-0.57,P<0.05)and isokinetic peak(r2=0.46-0.48,P<0.05)torques.Our results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy controls.Stiffness appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed muscles.The preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular velocities.All study procedures were approved by the Institutional Review Board at the Hunter Holmes McGuire VA Medical Center,USA(IRB#:02314)on May 3,2017.

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）.

The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.

One-year clinical study of NeuroR egen scaffold implantation following scar resection in complete chronic spinal cord injury patients

The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, Neuro Regen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5–4.5 cm were surgically resected in five complete chronic spinal cord injury(SCI) patients. The NeuroR egen scaffold along with autologous bone marrow mononuclear cells(BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or Neuro Regen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials(SSEP) from the lower limbs was also detected. The results indicate that scar resection and Neuro Regen scaffold transplantation could be a promising clinical approach to treating SCI.

Altered leukocyte gene expression after traumatic spinal cord injury:clinical implications

In addition to changes in motor and sensory function, individuals with spinal cord injury （SCI） experience immunological changes. These changes are clinically significant, as infections are the leading cause of death for this population. Along with increased infections, inflammation is commonly observed in persons with SCI, where it may promote many common medical consequences. These include elevated risk of cardio- vascular disease, impaired wound healing, diabetes and neuropathic pain. It has also been proposed that chronic inflammation dampens neurological recovery. In order to identify therapeutic strategies to im- prove immune function, we need a greater understanding of the molecular changes that occur in immune cells after SCI. The purpose of this mini-review is to discuss two recent studies that used functional genom- ics to investigate gene expression in circulating leukocytes isolated from persons with SCI. In the future, the molecular pathways that are altered after SCI may be targeted to improve immunological function, as well as overall health and functional recovery, after SCI.