Effects Of Spinal Cord Injury Research Articles

Trehalose–Carnosine Prevents the Effects of Spinal Cord Injury Through Regulating Acute Inflammation and Zinc(II) Ion Homeostasis

Spinal cord injury (SCI) leads to long-term and permanent motor dysfunctions, and nervous system abnormalities. Injury to the spinal cord triggers a signaling cascade that results in activation of the inflammatory cascade, apoptosis, and Zn(II) ion homeostasis. Trehalose (Tre), a nonreducing disaccharide, and l-carnosine (Car), (β-alanyl-l-histidine), one of the endogenous histidine dipeptides have been recognized to suppress early inflammatory effects, oxidative stress and to possess neuroprotective effects. We report on the effects of the conjugation of Tre with Car (Tre–car) in reducing inflammation in in vitro and in vivo models. The in vitro study was performed using rat pheochromocytoma cells (PC12 cell line). After 24 h, Tre–car, Car, Tre, and Tre + Car mixture treatments, cells were collected and used to investigate Zn2+ homeostasis. The in vivo model of SCI was induced by extradural compression of the spinal cord at the T6–T8 levels. After treatments with Tre, Car and Tre–Car conjugate 1 and 6 h after SCI, spinal cord tissue was collected for analysis. In vitro results demonstrated the ionophore effect and chelating features of l-carnosine and its conjugate. In vivo, the Tre–car conjugate treatment counteracted the activation of the early inflammatory cascade, oxidative stress and apoptosis after SCI. The Tre–car conjugate stimulated neurotrophic factors release, and influenced Zn2+ homeostasis. We demonstrated that Tre–car, Tre and Car treatments improved tissue recovery after SCI. Tre–car decreased proinflammatory, oxidative stress mediators release, upregulated neurotrophic factors and restored Zn2+ homeostasis, suggesting that Tre–car may represent a promising therapeutic agent for counteracting the consequences of SCI.

Effective Connectivity in Spinal Cord Injury-Induced Neuropathic Pain.

Aim: The aim of this study was to differentiate the effects of spinal cord injury (SCI) and central neuropathic pain (CNP) on effective connectivity during motor imagery of legs, where CNP is typically experienced. Methods: Multichannel EEG was recorded during motor imagery of the legs in 3 groups of people: able-bodied (N = 10), SCI with existing CNP (N = 10), and SCI with no CNP (N = 20). The last group was followed up for 6 months to check for the onset of CNP. Source reconstruction was performed to obtain cortical activity in 17 areas spanning sensorimotor regions and pain matrix. Effective connectivity was calculated using the directed transfer function in 4 frequency bands and compared between groups. Results: A total of 50% of the SCI group with no CNP developed CNP later. Statistically significant differences in effective connectivity were found between all groups. The differences between groups were not dependent on the frequency band. Outflows from the supplementary motor area were greater for the able-bodied group while the outflows from the secondary somatosensory cortex were greater for the SCI groups. The group with existing CNP showed the least differences from the able-bodied group, appearing to reverse the effects of SCI. The connectivities involving the pain matrix were different between able-bodied and SCI groups irrespective of CNP status, indicating their involvement in motor networks generally. Significance: The study findings might help guide therapeutic interventions targeted at the brain for CNP alleviation as well as motor recovery post SCI.

Historical development and contemporary use of neuromodulation in human spinal cord injury.

There is a long history of neuromodulation of the spinal cord after injury in humans with recent momentum of studies showing evidence for therapeutic potential. Nonrandomized, mechanistic, hypothesis-driven, small cohort, epidural stimulation proof of principle studies provide insight into the human spinal circuitry functionality and support the pathway toward clinical treatments. Individuals living with spinal cord injury can recover motor, cardiovascular, and bladder function even years after injury using neuromodulation. Integration of continuous feedback from sensory information, task-specific training, and optimized excitability state of human spinal circuitry are critical spinal mechanisms. Neuromodulation activates previously undetectable residual supraspinal pathways to allow intentional (voluntary) control of motor movements. Further discovery unveiled the human spinal circuitry integrated regulatory control of motor and autonomic systems indicating the realistic potential of neuromodulation to improve the capacity incrementally, but significantly for recovery after severe spinal cord injury. The discovery that both motor and autonomic function recovers with lumbosacral spinal cord placement of the electrode reveals exciting avenues for a synergistic overall improvement in function, health, and quality of life for those who have been living with the consequences of spinal cord injury even for decades.

Autonomic Consequences of Spinal Cord Injury

Autonomic Consequences of Spinal Cord Injury

Psychosocial Consequences of Spinal Cord Injury: A Narrative Review.

Consequences of a spinal cord injury (SCI) entail much more than damage to the spinal cord. The lives of people with SCI, along with those around them, experience profound long-lasting changes in nearly every life domain. SCI is a physical (biological) injury that is inextricably combined with various psychological and social consequences. The objective of this review is to present psychosocial challenges following SCI through the biopsychosocial model, beginning with acknowledgement of the larger societal effects of ableism and stigma before addressing the many unique psychosocial aspects of living with SCI. Included in this review are qualitative studies and systematic reviews on current psychosocial outcomes and consequences. This paper attempts to structure this information by dividing it into the following sections: relationships and family; changes in finances and employment; issues related to the person’s living situation; community reintegration; factors associated with mood and coping (e.g., depression, anxiety, substance use, and PTSD); self-harm behaviors (ranging from nonadherence to suicide); effects of traumatic brain injury; considerations regarding sexual health; aging with SCI; and concludes with a brief discussion about post-traumatic growth. Cultivating an understanding of the unique and interrelated psychosocial consequences of people living with SCI may help mitigate the psychosocial aftermath and serve as a reminder to providers to maintain a person-centered approach to care.

Application of Collagen-Based Scaffolds for the Treatment of Spinal Cord Injuries in Animal Models: A Literature Update

SCI is regarded as one of the most devastating central nervous system (CNS) injuries, exhibiting an alarmingly rising incidence rate, indirectly connected with the expansion of the global economy. The consequences of SCI are multidimensional: SCI injuries may result in permanent voluntary motor dysfunction and loss of sensation while incurring heavy economic and psychological burdens as part of the treatment. Thus, it is crucial to develop effective and suitable SCI treatment strategies. Collagen-based scaffold application is one of the most promising methods of SCI treatment.This review compiles newer bibliographical data regarding the application of collagen scaffolds for the treatment of Spinal cord injury (SCI) in animal models. Recently, several relevant studies have been carried out using carefully selected animals with similar pathophysiology to humans. In mouse, rat and canine models that have undergone transection or hemisection, the stump connection, the transplanted cell differentiation, and the elimination of glial scar are promising. Also, encouraging results have been found regarding the increased neuronal growth, the decreased collagen deposition, the behavioral recovery, the improved electrophysiology, and the enhanced axonal regeneration.

Locomotor activity and spasticity level of the limb in female mice with a spinal cord injury model

Spinal cord injuries (SCI) lead to large-scale physical, physiological, psychological and professional losses. Therefore, today, one of the urgent aims of neurophysiology is the study of the consequences of spinal cord injury. The most common type of SCI is a hemisection. For a comprehensive and detailed study of the functional post-traumatic recovery of the spinal cord, various hemisection options are developed. The aim of the study was to analyse the level of locomotor activity and changes in spasticity of the mice ipsilateral hindlimb (IH) after SCI. Materials and methods. The injury of the left-side spinal cord hemisection was modelled at the level of the lower thoracic segments (T10-T11) in female FVB mice. The locomotor activity and spasticity of the IH were determined every week using the Basso-Beattie-Bresnahan (ВВВ), the Basso (B) scales and the Ashworth scale during the first 1-12 weeks of the post-traumatic period. Results. At a later date (the 11th, 12th weeks) compared with the first weeks of the post-traumatic period, there was a marked recovery of the IH function: 4.39±0.61 points (out of 21 possible) on the BBB scale and 2.22±0.31 points (out of 9 possible) on the B scale. However, at all studied time interval after SCI, a consistently high level of hindlimb spasticity in experimental animals was noted, on the 12th week: 3.03±0.39 (out of 4 possible) on the Ashworth scale. Conclusions. After modelling spinal cord injury by hemisection, spontaneous post-traumatic recovery of locomotor activity was observed (since the 2nd week), which had scores corresponding to the early recovery phase. On the other hand, the levels of IH spasticity in mice were quite high throughout the entire study period, although already at the 2nd week there was a slight decrease in this parameter compared to the 1st week of the post-traumatic period.

Development of Electromyography Signal Contraction Detection Using the Double Threshold Method for Controlling Wheelchair

The consequence of spinal cord injury (SCI) is the malfunction of some parts of the body. This observation especially applies to trauma at the cervical level, because both patients' hands and legs are no longer functioning. The purpose of this study was to determine the mechanism of the comparator treshold system in electric wheelchairs for patients with paralysis. The research contribution is to get a treshold mechanism that can make a wheelchair run smoothly without being affected by the strength of the user's unstable muscle contractions. To set the muscle reference value, connect the transmitter to Android using USB Cable. On Android there are 2 settings modes, namely manual and auto settings. The method used in auto mode is the transmitter will take 100 contraction and 100 relaxation data and multiplied by certain constants to get the upper and lower threshold values. In setting the threshold manually, the value is set based on the strength of the patient's contractions that are displayed on Android manually. Where in the threshold setting manually obtained response 93.3% of forward movement, 100% of turn left movement, 100% of turn right movement and 93.3% of backward movement. Meanwhile, the threshold setting automatically gets 80% response for forward movements, 93.3% for turn left movements, 86.6% for turn right movements and 93.3% for backward movements. The results of the tapping into 4 parts of the muscle can be implemented to detect muscle contractions so that the wheelchair can move according to orders. The problem obtained in this study is that there are many tapping points on the face so that it interferes with the comfort and time of installing electrodes on the face, also the patient's muscle reference setting system on Android still needs the help of others. In the future, it is expected to reduce tapping points and improve the efficiency of muscle threshold settings.

Spinal cord injury impairs cardiac function due to impaired bulbospinal sympathetic control

Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury.

Clinical Utility of Diffusion Tensor Imaging as a Biomarker to Identify Microstructural Changes in Pediatric Spinal Cord Injury.

Lack of clarity about the neurological consequence of spinal cord injury (SCI) in children causes speculation about diagnoses, recovery potential, and treatment effectiveness. Diffusion tensor imaging (DTI) has shown promising results as a biomarker to evaluate spinal cord integrity at a microstructural level. To look at the difference between pediatric participants with and without SCI to determine which DTI metrics best categorize spinal cord tissue damage and to correlate DTI metrics with two clinical measures: Capabilities of the Upper Extremity Test (CUE-T) and Spinal Cord Independence Measure version III (SCIM-III). This single-site, prospective study included pediatric participants with SCI (n = 26) and typically developed (TD) control subjects (n = 36). All participants underwent two magnetic resonance imaging (MRI) scans on a 3T MR scanner. Participants with SCI also completed the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), CUE-T, and SCIM-III outcomes measures. This study found significant strength of association between fractional anisotropy (FA) and upper extremity muscle strength (UEMS) in participants with SCI. Most DTI parameters showed a significant difference between participants with SCI and TD participants and a moderate correlation with the CUE-T total score. Regional effects on group differences were found to be significant. This study demonstrates the strength of association between DTI parameters and clinical measures in the pedantic SCI population. It illustrates DTI as a potential biomarker of SCI location and severity in the pediatric SCI population.

Mesenchymal Stem Cells in the Treatment of Human Spinal Cord Injury: The Effect on Individual Values of pNF-H, GFAP, S100 Proteins and Selected Growth Factors, Cytokines and Chemokines.

At present, there is no effective way to treat the consequences of spinal cord injury (SCI). SCI leads to the death of neural and glial cells and widespread neuroinflammation with persisting for several weeks after the injury. Mesenchymal stem cells (MSCs) therapy is one of the most promising approaches in the treatment of this injury. The aim of this study was to characterize the expression profile of multiple cytokines, chemokines, growth factors, and so-called neuromarkers in the serum of an SCI patient treated with autologous bone marrow-derived MSCs (BM-MSCs). SCI resulted in a significant increase in the levels of neuromarkers and proteins involved in the inflammatory process. BM-MSCs administration resulted in significant changes in the levels of neuromarkers (S100, GFAP, and pNF-H) as well as changes in the expression of proteins and growth factors involved in the inflammatory response following SCI in the serum of a patient with traumatic SCI. Our preliminary results encouraged that BM-MSCs with their neuroprotective and immunomodulatory effects could affect the repair process after injury.

Evidence of treating spasticity before it develops: a systematic review of spasticity outcomes in acute spinal cord injury interventional trials.

Introduction: Spasticity is a common consequence of spinal cord injury (SCI), estimated to affect up to 93% of people living with SCI in the community. Problematic spasticity affects around 35% people with SCI spasticity. The early period after injury is believed to be the most opportune time for neural plasticity after SCI. We hypothesize that clinical interventions in the early period could reduce the incidence of spasticity. To address this, we evaluated the spasticity outcomes of clinical trials with interventions early after SCI.Methods: We performed a systematic review of the literature between January 2000 and May 2021 to identify control trials, in humans and animals, that were performed early after SCI that included measures of spasticity in accordance with PRISMA guidelines.Results: Our search yielded 1,463 records of which we reviewed 852 abstracts and included 8 human trial peer-reviewed publications and 9 animal studies. The 9 animal trials largely supported the hypothesis that early intervention can reduce spasticity, including evidence from electrophysiological, behavioral, and histologic measures. Of the 8 human trials, only one study measured spasticity as a primary outcome with a sample size sufficient to test the hypothesis. In this study, neuromodulation of the spinal cord using electric stimulation of the common peroneal nerve reduced spasticity in the lower extremities compared to controls.Conclusion: Given the prevalence of problematic spasticity, there is surprisingly little research being performed in the early period of SCI that includes spasticity measures, and even fewer studies that directly address spasticity. More research on the potential for early interventions to mitigate spasticity is needed.

Improvement in Neurogenic Bowel and Bladder Dysfunction Following Posterior Decompression Surgery for Cauda Equina Syndrome: A Prospective Cohort Study.

ObjectiveThe mechanisms of neurogenic bowel dysfunction (NBD) and neurogenic bladder (NB), which are major consequences of spinal cord injury and occasionally degenerative lumbar disease. The following in patients with cauda equina syndrome who underwent posterior decompression surgery was investigated: (1) the preoperative prevalence of NBD and NB, measured using the Constipation Scoring System (CSS) and International Prostate Symptoms Score (IPSS); (2) the degree and timing of postoperative improvement of NBD and NB. MethodsWe administered the CSS and IPSS in 93 patients before surgery and at 1, 3, 6, and 12 months postoperatively. We prospectively examined patient characteristics, Japanese Orthopaedic Association (JOA) score, and postoperative improvements in each score. ResultsThe prevalence of symptomatic defecation and urinary symptoms at admission were 37 patients (38.1%) and 31 patients (33.3%), respectively. Among the symptomatic patients with defecation problems, 12 patients had improved at 1 month, 13 at 3 months, 14 at 6 months, and 13 at 12 months postoperatively. Among the symptomatic patients with urinary problems, 5 patients improved at 1 month, 11 at 3 months, 6 at 6 months, and 10 at 1 year postoperatively. Comparing patients with improved versus unimproved in CSS, the degree of JOA score improvement was a significant prognosis factor (p<0.05; odds ratio, 1.05). ConclusionThe prevalence of symptomatic defecation and urinary symptoms in patients with cauda equina syndrome was 38.1% and 33.3%, respectively. Decompression surgery improved symptoms in 30%–50%. These effects were first observed 1 month after the operation and persisted up to 1 year.

Hyperbaric oxygenation therapy in treatment of traumatic spinal cord injury: a pilot study

Spinal cord traumatic injury as resulting persistent movement and sensory disorders is one of the most disabling consequences of traumatic factor impact on the human body. Despite a large number of experimental and clinical studies aimed at developing methods for restoring lost functions, there is no acceptable solution to the problem. One of the promising areas in the treatment and rehabilitation of this category of patients is the use of hyperbaric oxygenation (HBO). Experimental models have shown that HBO has a neuroprotective effect in spinal cord injury, but the results of clinical application of the method are still controversial. Objective: to determine the effectiveness of HBO in the complex therapy of victims with traumatic spinal cord injury and the feasibility of further study of this area. Materials and Methods: Study design is a pilot observational retrospective “case – control”. The database of patients with spinal cord injury who were hospitalized at Romodanov Neurosurgery Institute in the period from 2010 to 2020 were used for the analysis. When selecting a control for each clinical case, the following factors were considered: gender, age, circumstances of injury, type of damage to the osteoligamentous apparatus, level of neurological deficit, degree of damage and compression of the spinal cord, time elapsed from the moment of injury to surgery. 28 "case ‒ control" pairs were analyzed. The main criterion for therapy effectiveness was the change in the functional class according to the ASIA scale. Results. Positive dynamics was registered in 57% of victims, including in the group of patients receiving HBO therapy - in 71%, in the control group - in 43%. HBO therapy in the postoperative period significantly affects the dynamics of regression of neurological disorders (p=0.0295). The odds ratio is 3.333 (95% confidence interval - 1.098‒10.116, p=0.0335). The calculation of the odds ratio, adjusted for additional analyzed factors, showed a more pronounced efficiency - 4.519 (95% confidence interval - 1.279‒15.962, p=0.0192). Conclusions. The obtained results indicate that usage of HBO as a method of complex therapy for traumatic spinal cord injury is promising for further study in order to determine the effectiveness of the method, the optimal timing of treatment initiation in the postoperative period and its duration.

Ecto-5'-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway.

Spinal cord injury (SCI) is a serious affliction that can lead to insufficient blood supply to the spinal cord, resulting in nutrient and energy deficiency in nerve cells such as neurons. In the present study, a spinal cord injury mouse model was constructed using wild-type (WT) and ecto-5'-nucleotidase (CD73)-/- mice. The results of TUNEL and immunofluorescence assays indicated that the apoptosis of neurons in CD73-/- mice was increased after spinal cord injury. Dorsal root ganglion (DRG) neurons from WT and CD73-/- mice were cultured in low glucose and hypoxic conditions to simulate the effects of spinal cord injury on neurons. Subsequently, a western blot assay was used to detect the expression of CD73, caspase-3 and Bcl-2. Flow cytometry was used to detect cell apoptosis and the corresponding kits were used to detect changes in lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), adenosine triphosphate (ATP) and cell activity. The results revealed that the apoptosis level of CD73-overexpressing DRG neurons was decreased under anoxia and glucose deficiency. The release of LDH, MDA and the production of ROS in CD73 DRG neurons was decreased, while the synthesis of ATP, the activity of SOD and cell activity increased after hypoxia-hypoglycemia treatment. Additional cellular studies demonstrated that blocking the expression and hydrolase activity of CD73 with α,β-methylene ADP (APCP) could counteract the protective effect of CD73 on neuronal apoptosis, while adenosine (Ado) could rescue the increased apoptosis caused by CD73 deletion. In addition, the cAMP/ protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathway was also positively regulated by CD73 and Ado. In conclusion, CD73 could inhibit DRG neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway.

Parallel Metabolomic Profiling of Cerebrospinal Fluid, Plasma, and Spinal Cord to Identify Biomarkers for Spinal Cord Injury

Loss of physical and emotional health due to spinal cord injury (SCI) has been rapidly increasing worldwide. Effective evaluation of the severity of SCI is crucial to its prognosis. Herein, we constructed rat models of SCI with four different degrees of injury (sham group, light injury group, moderate injury group, and heavy injury group), using the surgical approach. Cerebrospinal fluid (CSF), plasma, and spinal cord were sampled at the sub-acute spinal cord (72 h post-injury) from each rat. The LC–MS-based metabolic profiling of these samples was performed according to a universal metabolome standard (UMS). The results demonstrated that 130, 104, and 128 metabolites were significantly altered within the CSF, plasma, and spinal cord samples, respectively. Among them, there were four differential metabolites, including uric acid, phosphorycholine, pyridoxine, and guanidoacetic acid, which were commonly identified within the CSF, plasma, and spinal cord samples. Further pathway analysis of these differential metabolites demonstrated a disturbance in the metabolism of glyoxylate and dicarboxylate and glycine, serine, and threonine which were associated with pathophysiologic consequence of spinal cord injury. In particular, phosphorycholine, pyridoxine, and guanidoacetic acid demonstrated a relationship with SCI severity. Thus, they could be utilized as potential metabolite biomarkers for SCI severity assessment.

First experience with chronic epidural spinal cord stimulation in Khanty-Mansi autonomous okrug — clinical observations

Purpose of the work. The article is devoted to the first experience of epidural stimulation in the Khanty-Mansiysk Autonomous Okrug at the budgetary institution Surgut Clinical Trauma Hospital. Clinical examples are presented for two main indications for the application of this technique (disease of the operated spine, a consequence of spinal cord injury in combination with chronic neuropathic pain syndrome).&#x0D; Research methods. An assessment of the intensity of pain syndrome was given according to a visual analogue scale, the Pain Detect questionnaire; indicators of anxiety, depression on the HADS scale; quality of life according to the Oswestry questionnaire for a follow-up period of 6-12 months in patients with chronic epidural stimulation.&#x0D; Results. A positive assessment of the action during test neurostimulation was 63.3% (38 patients). Of the established permanent systems, a good result was achieved and persisted for 12 months or more in 96% (24 patients). It was necessary to change the stimulation parameters in 13% (3 patients). Revision of permanent systems was performed in 20% (5 patients), due to the progression of the degenerative-dystrophic process of the spine, damage and migration of system elements.&#x0D; Conclusions. Chronic epidural spinal cord stimulation has established itself as a personalized, highly effective, minimally invasive and safe method of treating chronic neuropathic pain syndromes. Multicomponent corrective action is of scientific interest and requires further study.

Advances in olfactory ensheathing cells for the treatment of spinal cord injury

Spinal cord injury is a highly disabled neurological disease, and there is still a lack of effective treatments. Studies have proved that olfactory ensheathing cells are one of the ideal seed cells for promoting nerve regeneration after spinal cord injury. Olfactory ensheathing cells can promote axonal germination and elongation through secretion, interaction with astrocytes, regulation of inflammatory reaction, migration characteristics, myelination, anti-oxidation, lipid regulation and other channels. Thus olfactory ensheathing cells play the role of neuroprotection and nerve repair. In recent years, some studies have used bioengineering, tissue engineering, reprogramming and other technologies to enhance the efficacy of olfactoryensheathing cells from different aspects, thereby providing new therapeutic strategies for optimizing the cell therapy of spinal cord injury. This article will summarize the mechanism of olfactory ensheathing cells in repairing spinal cord injury, and review the progress of optimizing strategy of olfactory ensheathing cells in treating spinal cord injury recently, so as to provide new research ideas for the further developing the repair potential of olfactory ensheathing cells and optimize the cell therapy effect of spinal cord injury.

Effect of electroacupuncture on inhibition of inflammatory response and oxidative stress through activating ApoE and Nrf2 in a mouse model of spinal cord injury.

IntroductionElectroacupuncture protects neurons and myelinated axons after spinal cord injury by mitigating the inflammatory response and oxidative stress, but how it exerts these effects is unclear.Methods and resultsSpinal cord injury was induced in C57BL/6 wild‐type and apolipoprotein E (ApoE) knockout (ApoE –/–) mice, followed by electroacupuncture or ApoE mimetic peptide COG112 treatment. Mice with spinal cord injury suffered loss of myelinated axons and hindlimb motor function through the detections of Basso mouse scale, histology, and transmission electron microscopy; electroacupuncture partially reversed these effects in wild‐type mice but not in ApoE–/– mice. Combining exogenous ApoE administration with electroacupuncture significantly mitigated the effects of spinal cord injury in both mouse strains, and these effects were associated with up‐regulation of anti‐inflammatory cytokines and down‐regulation of pro‐inflammatory cytokines which were detected by quantitative reverse transcription‐polymerase chain reaction. Combination treatment also reduced oxidative stress by up‐regulating ApoE and Nrf2/HO‐1 signaling pathway through the detections of immunofluorescence and western blot analysis.ConclusionsThese results suggest that electroacupuncture protects neurons and myelinated axons following spinal cord injury through an ApoE‐dependent mechanism.

Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery.

Microglia are resident myeloid cells of the CNS. Recently, single-cell RNA sequencing (scRNAseq) has enabled description of a disease-associated microglia (DAM) with a role in neurodegeneration and demyelination. In this study, we use scRNAseq to investigate the temporal dynamics of immune cells harvested from the epicenter of traumatic spinal cord injury (SCI) induced in female mice. We find that as a consequence of SCI, baseline microglia undergo permanent transcriptional reprogramming into a previously uncharacterized subtype of microglia with striking similarities to previously reported DAM as well as a distinct microglial state found during development. Using a microglia depletion model we showed that DAM in SCI are derived from baseline microglia and strongly enhance recovery of hindlimb locomotor function following injury.SIGNIFICANCE STATEMENT Although disease-associated microglia (DAM) have been the subject of strong research interest during recent years (Keren-Shaul, 2017; Jordão, 2019), their cellular origin and their role in “normal” acute injury processes is not well understood. Our work directly addresses the origin and the role of DAM in traumatic injury response. Further, we use a microglia depletion model to prove that DAM in spinal cord injury (SCI) are indeed derived from homeostatic microglia, and that they strongly enhance recovery. Thus, in this work we significantly expand the knowledge of immune response to traumatic injury, demonstrate the applicability to human injury via our unique access to injured human spinal cord tissue, and provide the community with a comprehensive dataset for further exploration.