Effects Of Spinal Cord Injury Research Articles

Spinal cord injury: pathogenetic principles of molecular and cellular therapy

Spinal cord injury: pathogenetic principles of molecular and cellular therapy

Neuromuscular consequences of spinal cord injury: New mechanistic insights and clinical considerations.

The spinal cord facilitates communication between the brain and the body, containing intrinsic systems that work with lower motor neurons (LMNs) to manage movement. Spinal cord injuries (SCIs) can lead to partial paralysis and dysfunctions in muscles below the injury. While traditionally this paralysis has been attributed to disruptions in the corticospinal tract, a growing body of work demonstrates LMN damage is a factor. Motor units, comprising the LMN and the muscle fibers with which they connect, are essential for voluntary movement. Our understanding of their changes post-SCI is still emerging, but the health of motor units is vital, especially when considering innovative SCI treatments like nerve transfer surgery. This review seeks to collate current literature on how SCI impact motor units and explore neuromuscular clinical implications and treatment avenues. SCI reduced motor unit number estimates, and surviving motor units had impaired signal transmission at the neuromuscular junction, force-generating capacity, and excitability, which have the potential to recover chronically, yet the underlaying mechanisms are unclear. Furthermore, electrodiagnostic evaluations can aid in assessing the health lower and upper motor neurons, identify suitable targets for nerve transfer surgeries, and detect patients with time sensitive injuries. Lastly, many electrodiagnostic abnormalities occur in both chronic and acute SCI, yet factors contributing to these abnormalities are unknown. Future studies are required to determine how motor units adapt following SCI and the clinical implications of these adaptations.

Improvement of Functional State of Patients after Spinal Cord Injury During Epidural Electrical Stimulation: Prospective Study

the lack of convincing evidence of a therapeutic effect.
 AIM. To evaluate the effect of complex rehabilitation using EPS and activation of the proprioceptive apparatus on the indicators of the functional state of patients with long-term consequences of spinal cord injury with partial spinal cord injury.
 MATERIALS AND METHODS. A prospective study was conducted with the participation of 29 patients with long-term consequences of spinal cord injury with partial spinal cord injury. The catamnesis of the disease was 3.7 ± 0.5 years. Comprehensive rehabilitation included epidural electrical stimulation by implantable electrode and activation of the proprioceptive apparatus. The neurological (ASIA scale) and functional (CSIM III scale) status of the patient was analyzed. Motor function was evaluated using 10-meter Walk test; M-responses of limb muscles — using electromyography, temperature and pain sensitivity — using esthesiometry.
 RESULTS. An increase in muscle strength and M-response of the muscles of the extremities, normalization of the motor deficit index, reduction of the walking test time, increase in movement speed and the patient’s independence index were revealed. There is an improvement in temperature and pain sensitivity at the level of damage and in the dermatomes located distally. The effect decreases in dermatomes far from the level of the electrode installation; but with increase in the number of courses the effect increases.
 DISCUSSION. The results obtained indicate that this rehabilitation complex, including UES, has a positive effect on the functioning of both the motor and sensitive spheres.
 CONCLUSION. Application of EES and activation of the proprioceptive apparatus improves the functional condition of sensorimotor sphere in the long-term consequences of spinal cord injury with partial spinal cord damage. Repeated rehabilitation courses have cumulative effect.

Superparamagnetic Iron Oxide Nanoparticle Implantation and Magnetic Field Exposure Modulate Bone Microarchitecture Following Spinal Cord Injury in Adult Male Rats

Background: Osteoporosis is one of the detrimental effects of spinal cord injury (SCI), leading to bone loss. It has already been established that superparamagnetic nanoparticles when exposed to an external magnetic field (MF) show strong magnetisation and promote locomotor recovery. Purpose: The aim of the present study is to explore the role of magnetised nanoparticles in ameliorating SCI-induced osteoporosis. Methods: The rats were divided into Sham, SCI, SCI+MF, SCI+V, SCI+NP and SCI+NP+MF groups. A complete transection was performed at the T13 level, followed by iron oxide nanoparticle implantation along with MF exposure for 7 or 14 days. Results: A significant increase in locomotor score was evident at day 5 in all groups except in the SCI+V group, and at day 7, all groups showed a significant increase in Basso, Beattie and Bresnahan score as compared to the pre-surgery score at week 1 of the study period. A significant decrease in bone volume/total volume ratio and trabecular thickness and increase in trabecular separation were observed in all groups as compared to Sham. A significant increase in trabecular thickness in the SCI+NP+MF group as compared to the SCI+MF group was observed after one week. After two weeks, the SCI+MF group showed a significant increase in locomotor scores at days 5 and 13 as compared to the SCI, SCI+V and SCI+NP groups. Bone loss was significantly observed in all groups except SCI+MF, as compared to Sham. Cortical bone showed no significant change at both time points. On histopathological examination of the spinal cord, we observed significant improvement in lesion volume in SCI+MF and SCI+NP+MF groups after one week, whereas only the SCI+NP+MF group showed a significant decrease after two weeks. Conclusion: Electromagnetic field stimulation partially restored bone architecture after superparamagnetic nanoparticle implantation, which may be due to reduced lesion volume and improved locomotor behaviour.

The Effect of Concomitant Spinal Cord Injury on Postoperative Health-related Quality of Life After Traumatic Subaxial Cervical Spine Injuries: A Nationwide Registry Study

ObjectiveTo evaluate the effect of spinal cord injury (SCI) on the health-related quality of life (HRQoL) in patients surgically treated for traumatic subaxial cervical spine injuries and investigate the agreement between objective neurologic outcomes and patient reported outcome measures (PROMs) in that context. Study DesignObservational study on prospectively collected multi-institutional registry data. SettingSweden. ParticipantsPatients with traumatic subaxial spine injuries identified in the Swedish Spine Registry (Swespine) between 2006 and 2016. InterventionsAnterior, posterior, or anteroposterior cervical fixation surgery. Main OutcomesPatient-reported outcome measures (PROMs) consisting of EQ-5D-3Lindex and Neck Disability Index (NDI). ResultsAmong the 418 identified patients, 93 (22%) had a concomitant SCI. In this group, 30 (32%) had a complete SCI (Frankel A), and the remainder had incomplete SCIs (17%) Frankel B; 25 (27%) Frankel C; 22 (24%) Frankel D. PROMs significantly correlated with the Frankel grade (P<.001). However, post hoc analysis revealed that the differences between adjacent Frankel grades failed to reach both statistical and clinical significance. On univariable linear regression, the Frankel grade was a significant predictor of a specific index derived from the EQ-5D-3L questionnaire (EQ-5D-3Lindex) at 1, 2, and 5 years postoperatively as well as the NDI at 1 and 2 years postoperatively (P<.001). Changes of PROMs over time from 1, to 2, and 5 years postoperatively did not reach statistical significance, regardless of the presence and degree of SCI (P>.05). ConclusionOverall, the Frankel grade significantly correlated with the EQ-5D-3Lindex and NDI and was a significant predictor of PROMs at 1, 2, and 5 years. PROMs were stable beyond 1 year postoperatively regardless of the severity of the SCI.

Prediction of early bladder outcomes after spinal cord injury: The HALT score.

Neurogenic bladder (NB) is a prevalent and debilitating consequence of spinal cord injury (SCI). Indeed, the accurate prognostication of early bladder outcomes is crucial for patient counseling, rehabilitation goal setting, and personalized intervention planning. A retrospective exploratory analysis was conducted on a cohort of consecutive SCI patients admitted to a rehabilitation facility in China from May 2016 to December 2022. Demographic, clinical, and electrophysiological data were collected within 40 days post-SCI, with bladder outcomes assessed at 3 months following SCI onset. The present study enrolled 202 SCI patients with a mean age of 40.3 ± 12.3 years. At 3 months post-SCI, 79 participants exhibited complete bladder emptying. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analyses identified the H-reflex of the soleus muscle, the American Spinal Injury Association Lower Extremity Motor Score (ASIA-LEMS), and the time from lesion to rehabilitation facility (TLRF) as significant independent predictors for bladder emptying. A scoring system named HALT was developed, yielding a strong discriminatory performance with an area under the receiver operating characteristics curve (aROC) of 0.878 (95% CI: 0.823-0.933). A simplified model utilizing only the H-reflex exhibited excellent discriminatory ability with an aROC of 0.824 (95% CI: 0.766-0.881). Both models demonstrated good calibration via the Hosmer-Lemeshow test and favorable clinical net benefits through decision curve analysis (DCA). In comparison to ASIA-LEMS, both the HALT score and H-reflex showed superior predictive accuracy for bladder outcome. Notably, in individuals with incomplete injuries, the HALT score (aROC = 0.973, 95% CI: 0.940-1.000) and the H-reflex (aROC = 0.888, 95% CI: 0.807-0.970) displayed enhanced performance. Two reliable models, the HALT score and the H-reflex, were developed to predict bladder outcomes as early as 3 months after SCI onset. Importantly, this study provides hitherto undocumented evidence regarding the predictive significance of the soleus H-reflex in relation to bladder outcomes in SCI patients.

Epigenetic processes associated with neonatal spinal transection.

In early development, the spinal cord in healthy or disease states displays remarkable activity-dependent changes in plasticity, which may be in part due to the increased activity of brain derived neurotrophic factor (BDNF). Indeed, BDNF delivery has been efficacious in partially ameliorating many of the neurobiological and behavioral consequences of spinal cord injury (SCI), making elucidating the role of BDNF in the normative developing and injured spinal cord a critical research focus. Recent work in our laboratory provided evidence for aberrant global and locus-specific epigenetic changes in methylation of the Bdnf gene as a consequence of SCI. In the present study, animals underwent thoracic lesions on P1, with cervical and lumbar tissue being later collected on P7, P14, and P21. Levels of Bdnf expression and methylation (exon IX and exon IV), in addition to global methylation levels were quantified at each timepoint. Results indicated locus-specific reductions of Bdnf expression that was accompanied by a parallel increase in methylation caudal to the injury site, with animals displaying increased Bdnf expression at the P14 timepoint. Together, these findings suggest that epigenetic activity of the Bdnf gene may act as biomarker in the etiology and intervention effort efficacy following SCI.

Contribution of mechanoreceptors to spinal cord injury-induced mechanical allodynia.

Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.

Chronic pain among Lebanese individuals with spinal cord injury: Pain interference and impact on quality of life.

Background: Chronic pain is one of the most disabling consequences of spinal cord injury (SCI). Although studies have identified a link between chronic pain and decreased quality of life (QOL) among this population, few studies have looked into the experience of chronic pain in Lebanese individuals with SCI and the impact of pain characteristics on QOL. Thus, the present study evaluated the chronic pain experience and its associated factors among Lebanese individuals with SCI in order to determine the impact of pain on QOL. Methods: A cross-sectional study was conducted on 81 Lebanese individual with SCI between August 1st and October 31, 2022. The collected information included sociodemographic characteristics, SCI-related information, pain-related variables, and the 12-item Short Form Health Survey (SF-12). Factors associated with pain interference were evaluated using a linear regression model. One-way ANOVA and independent sample t-test were used to evaluate the association of different baseline and pain characteristics with QOL. Results: In the present study, 81.5% of participants reported chronic pain with the majority of them having neuropathic pain type. Employment status (P = 0.034), type of pain (P = 0.009), and pain severity (P = 0.028) were significantly associated with pain interference. Unemployed participants and those with severe chronic pain, particularly neuropathic pain, had lower QOL. Conclusion: Chronic pain was found to be highly prevalent among Lebanese patients with SCI. Pain interference and QOL were significantly affected by employment status and pain type. Therefore, targeting chronic pain and its associated factors in rehabilitation practice is warranted.

Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications.

The majority of research on the long-term effects of spinal cord injury (SCI) has primarily focused on neuropathic pain (NP), psychological issues, and sensorimotor impairments. Among SCI patients, mood disorders, such as anxiety and depression, have been extensively studied. It has been found that chronic stress and NP have negative consequences and reduce the quality of life for individuals living with SCI. Our review examined both human and experimental evidence to explore the connection between mood changes following SCI and inflammatory pathways, with a specific focus on NLRP3 inflammasome signaling. We observed increased proinflammatory factors in the blood, as well as in the brain and spinal cord tissues of SCI models. The NLRP3 inflammasome plays a crucial role in various diseases by controlling the release of proinflammatory molecules like interleukin 1β (IL-1β) and IL-18. Dysregulation of the NLRP3 inflammasome in key brain regions associated with pain processing, such as the prefrontal cortex and hippocampus, contributes to the development of mood disorders following SCI. In this review, we summarized recent research on the expression and regulation of components related to NLRP3 inflammasome signaling in mood disorders following SCI. Finally, we discussed potential therapeutic approaches that target the NLRP3 inflammasome and regulate proinflammatory cytokines as a way to treat mood disorders following SCI.

Medical convergence technology in the system of comprehensive rehabilitation of children with neurotrauma: our experience of implementation (with case report)

BACKGROUND: The annual increase of childhood trauma with severe consequences is 2% per year (WHO, 2020/21). This motivates rehabilitation specialists to search for new technologies and effective approaches. Timely resuscitation, early specialized and comprehensive rehabilitation care largely determine the outcome of a serious injury and prevent serious consequences. In this context, medical convergent technologies used to provide effective medical care become particularly relevant. This article of scientific, methodological and applied nature is devoted to the description of medical convergent technology implemented in the system of comprehensive rehabilitation care of children with severe neurotrauma.&#x0D; AIM: The aim of the study was to substantiate and develop an effective rehabilitation technology at the level of unified (convergent) interdisciplinary managerial and clinical-diagnostic medical solutions in rehabilitation of children with severe injuries.&#x0D; MATERIALS AND METHODS: Children, aged 2–17, (n=420) with consequences after severe traumatic injuries who were admitted to the Clinical and Research Institute of Emergency Pediatric Surgery and Trauma (Moscow) for treatment and rehabilitation in 2018–2022 with diagnoses: traumatic brain injury, consequences of spinal cord injury, combined trauma, mine-explosive trauma, severe skeletal trauma, infected extensive wounds. More than 300 of these patients had neurotrauma. The researchers used: literature sources on the discussed problem, findings of objective and subjective examinations (clinical examination, neuroimaging, neurofunctional, laboratory, radiation, instrumental as well as questionnaires, surveys, scales; electronic medical histories). To develop medical convergent technology, rehabilitation diagnosis, potentials and prognostic options according to the decision-making algorithm developed by physicians/specialists as well as differentiated personified rehabilitation programs were used. While developing these programs, the researchers assessed specific features of the injury, disease course, severity and level of functional impairment, activity and participation expressed in the criteria of the International Classification of Functioning, Disability and Health.&#x0D; RESULTS: The researchers have enunciated the essence of the medical convergent technology in the rehabilitation of children after severe injuries as convergence, the alliance of interests from different fields, process of integration of traditional and new approaches which are united by a single goal of managing patients after severe traumatic injuries.&#x0D; CONCLUSION: An interdisciplinary/multidisciplinary approach with medical convergent technology component in restoring children after severe trauma allows to optimize the rehabilitation process and the patient’s routing within this process. Integrity and continuity in management and rehabilitation of injured patients as well as step-by-step approach, help physicians to choose the most effective tactics.

Unrecognised autonomic dysreflexia in neurogenic lower urinary tract dysfunction with spinal cord injury as a reason for admission to a cardiac surgical unit

BACKGROUND: In Russia, spinal cord injury occurs in 0.7–6.8% of total injuries. Due to emergence of new rehabilitation protocols, it is extremely important to know the time of occurrence of consequences of spinal cord injury and adequate diagnosis of complications, which allows timely identification of life-threatening conditions of one of the body systems.&#x0D; Clinical case description. We present a clinical case of autonomic dysreflexia in neurogenic lower urinary tract dysfunction after traumatic cervical spinal cord injury in a 17-year-old girl. In traumatic spinal cord injury above the level of the sixth thoracic vertebra, autonomic dysreflexia as a variant of autonomic dysfunction is a common complication. This clinical case will be of interest to clinicians of all specialties who encounter patients with spinal cord injury. It is shown that misinterpreted symptoms of increased blood pressure during bladder filling were the cause of observation and treatment by a cardiologist for arterial hypertension, as well as hospitalization in the cardiac surgery department for planned surgical treatment of renal artery stenosis, which was thought to be the cause of the episodic increases in blood pressure. Lack of knowledge about the presence of autonomic dysfunction in spinal cord injury patients may have led to unnecessary surgical treatment. During the joint management of the patient with a pediatric cardiac surgeon, signs of autonomic dysreflexia were detected against the background of traumatic spinal cord disease at the level of the cervical spine, hypotensive treatment and planned surgical intervention were canceled.&#x0D; Conclusion. Subsequently, an adequate regimen of periodic bladder catheterization and antimuscarinic drug therapy was prescribed, which successfully reduced the dysreflexia.

Exercise and aerobic capacity in individuals with spinal cord injury: A systematic review with meta-analysis and meta-regression.

A low level of cardiorespiratory fitness [CRF; defined as peak oxygen uptake ([Formula: see text]O2peak) or peak power output (PPO)] is a widely reported consequence of spinal cord injury (SCI) and a major risk factor associated with chronic disease. However, CRF can be modified by exercise. This systematic review with meta-analysis and meta-regression aimed to assess whether certain SCI characteristics and/or specific exercise considerations are moderators of changes in CRF. Databases (MEDLINE, EMBASE, CENTRAL, and Web of Science) were searched from inception to March 2023. A primary meta-analysis was conducted including randomised controlled trials (RCTs; exercise interventions lasting >2 weeks relative to control groups). A secondary meta-analysis pooled independent exercise interventions >2 weeks from longitudinal pre-post and RCT studies to explore whether subgroup differences in injury characteristics and/or exercise intervention parameters explained CRF changes. Further analyses included cohort, cross-sectional, and observational study designs. Outcome measures of interest were absolute (A[Formula: see text]O2peak) or relative [Formula: see text]O2peak (R[Formula: see text]O2peak), and/or PPO. Bias/quality was assessed via The Cochrane Risk of Bias 2 and the National Institute of Health Quality Assessment Tools. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random effects models were used in all meta-analyses and meta-regressions. Of 21,020 identified records, 120 studies comprising 29 RCTs, 67 pre-post studies, 11 cohort, 7 cross-sectional, and 6 observational studies were included. The primary meta-analysis revealed significant improvements in A[Formula: see text]O2peak [0.16 (0.07, 0.25) L/min], R[Formula: see text]O2peak [2.9 (1.8, 3.9) mL/kg/min], and PPO [9 (5, 14) W] with exercise, relative to controls (p < 0.001). Ninety-six studies (117 independent exercise interventions comprising 1,331 adults with SCI) were included in the secondary, pooled meta-analysis which demonstrated significant increases in A[Formula: see text]O2peak [0.22 (0.17, 0.26) L/min], R[Formula: see text]O2peak [2.8 (2.2, 3.3) mL/kg/min], and PPO [11 (9, 13) W] (p < 0.001) following exercise interventions. There were subgroup differences for R[Formula: see text]O2peak based on exercise modality (p = 0.002) and intervention length (p = 0.01), but there were no differences for A[Formula: see text]O2peak. There were subgroup differences (p ≤ 0.018) for PPO based on time since injury, neurological level of injury, exercise modality, and frequency. The meta-regression found that studies with a higher mean age of participants were associated with smaller changes in A[Formula: see text]O2peak and R[Formula: see text]O2peak (p < 0.10). GRADE indicated a moderate level of certainty in the estimated effect for R[Formula: see text]O2peak, but low levels for A[Formula: see text]O2peak and PPO. This review may be limited by the small number of RCTs, which prevented a subgroup analysis within this specific study design. Our primary meta-analysis confirms that performing exercise >2 weeks results in significant improvements to A[Formula: see text]O2peak, R[Formula: see text]O2peak, and PPO in individuals with SCI. The pooled meta-analysis subgroup comparisons identified that exercise interventions lasting up to 12 weeks yield the greatest change in R[Formula: see text]O2peak. Upper-body aerobic exercise and resistance training also appear the most effective at improving R[Formula: see text]O2peak and PPO. Furthermore, acutely injured, individuals with paraplegia, exercising for ≥3 sessions/week will likely experience the greatest change in PPO. Ageing seemingly diminishes the adaptive CRF responses to exercise training in individuals with SCI. PROSPERO: CRD42018104342.

“Meet the patient” session: a strategy to teach medical students about autonomic dysfunction after spinal cord injury

Dysregulation of the autonomic nervous system is an important long-term consequence of spinal cord injury (SCI). Yet, there is a scarcity of teaching resources about this topic for preclinical medical students. Given the association of SCI sequelae with emergency complications and mortality, it is imperative to equip medical students with the ability to recognize them. We designed a “Meet the Patient” (MTP) session with the primary goal to enhance student learning about SCI sequelae by interacting with patients and listening to real-life stories. The session primarily focused on recognizing triggers and symptoms of autonomic dysreflexia (AD) and discussing the loss of bowel and bladder control, while providing opportunities to learn more about living with SCI from patients’ real-life experiences. During the MTP session, patients living with SCI discussed their experience with AD, neurogenic bowel and bladder, and spasticity, among other SCI sequelae. We evaluated the outcomes of the MTP session by assessing numerical performance in questions related to the session (post-session quiz and final exam) and students’ satisfaction (post-session survey) in two subsequent academic years. The numerical performance in SCI-questions was high for both academic years (and higher than national average for the final exam question), indicating adequate acquisition of knowledge. Satisfaction with the session was high, with most students indicating that the session helped them consolidate their knowledge about the topic.

The influence of walking in an exoskeleton on rehabilitation of patients with spinal cord injury consequences

Objective: to substantiate the expediency of including training walking in an exoskeleton in the complex rehabilitation of patients with severe motor dysfunctions of the lower limbs due to spinal cord injury (SCI).Methods: 120 patients (84 men and 36 women, age 37.1 ± 8.40 years) with the consequences of SCI at the level of thoracic and lumbar spine who were in the hospital at the second stage of medical rehabilitation were examined. The duration of injury ranged from 1 year to 19 years (77.8 ± 4.05 months). All patients were divided into two groups (80 and 40 patients), comparable by sex, age, duration and severity of injury. Training walking in exoskeleton have been added in the group I rehabilitation program. ASIA, SCIM III scales and SF-36 quality of life questionnaire were used to evaluate the effectiveness of the rehabilitation measures.Results: there was an increase in the total score on SCIM III by 3.20 ± 0.50 (p = 0.05) in group I, which indicates an increase in the level of functioning and daily activity of patients. Positive dynamics was revealed when assessing the quality of life using SF-36 questionnaire: sum index reflecting the psychological component of health increased from 56,0 to 59,5 points (p = 0,05). Group II also showed positive dynamics of the analyzed indicators, but the changes by the end of the rehabilitation course were not statistically significant.Conclusion: the use of exoskeleton training walking at the second stage of medical rehabilitation increases the effectiveness of rehabilitation measures and improves the quality of life of patients with severe motor dysfunctions of the lower limbs due to spinal cord injury (SCI).

Features of neuroglia at the epicenter of spinal cord contusion injury and at distant areas in mini-pigs

Aim. To determine the delayed (after 2 months) effect of spinal cord injury (SCI) in the lower thoracic region in the mini-pigs on the morphologic state of macro- and microglia in nearby and remote caudal areas. Materials and methods. Sexually mature female Vietnamese pot-bellied pigs were randomly divided into two groups: SCI (n = 3) and intact (n = 3). Dosed contusion SCI was modelled at the level of the Th8–Th9 vertebrae, and transverse cryostat sections of the caudal segment adjacent to the epicenter of injury and the lumbar thickening (L4–S2) were examined 2 months later. The expression of astrocyte markers (glial fibrillary acidic protein, GFAP) and microglial markers (ionized calcium-binding adapter molecule 1, Iba1) was assessed as the relative immunopositive area occupied by cells. When counting the number of oligodendroglial cells (oligodendrocyte transcription factor 2, Olig2), the presence of nuclei detectable with 4’,6-diamidino-2-phenylindole (DAPI) was taken into account.Results. After SCI, an increase in the relative areas occupied by GFAP-positive astrocytes and Iba1-positive microglia and a decrease in Olig2-positive oligodendrocytes were detected in both the lesion area and lumbar thickening. In both regions, 2 months after SCI, the proportion of astrocytes was not significantly different in the anterior horns and doubled in the posterior horns. Microglia cells with SCI were 2.5 times more in the anterior horns of both regions and in the posterior horns of the lumbar thickening, while the presence of microglia increased slightly (1.2 times) in the posterior horns in the SCI region. The number of oligodendrocytes decreased in the area of the epicenter of SCI in the anterior and posterior horns by 1.5–1.75 times, and in the lumbar thickening more significantly: the number decreased by 2.5 times in the anterior horn and 5.5 times in the posterior horn. Conclusion. The results of the study revealed a similar pattern of macro- and microglial cell distribution both in the SCI region and in remote areas. The obtained data testify to the necessity to take into account the state of the areas of nervous tissue remote from the epicenter of SCI when stimulating neuroregeneration in such patients

Pramipexole has a neuroprotective effect in spinal cord injury and upregulates D2 receptor expression in the injured spinal cord tissue in rats.

Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1β.

Neuronal differentiation and inhibition of glial differentiation of murine neural stem cells by pHPMA hydrogel for the repair of injured spinal cord

Currently, several therapeutic methods of treating the effects of spinal cord injury (SCI) are being considered. On the one hand, transplantation of stem cells (SCs), in particular, neural stem/progenitor cells (NSPCs), is promising, as these cells have the potential to differentiate into nervous tissue cells, able to enhance endogenous regeneration and prevent the development of inflammatory processes. On the other hand, it is quite promising to replace the damaged nervous tissue with synthetic matrices, in particular hydrogels, which can create artificial conditions for the regenerative growth of injured nerve fibers through the spinal cord injury area, i.e. stimulate and support axonal regeneration and myelination. In this work, we combined both of these novel approaches by populating (injecting or rehydrating) a heteroporous pHPMA hydrogel (NeuroGel) with murine hippocampal NSPCs. Being inside the hydrogel (10 days of cultivation), NSPCs were more differentiated into neurons: 19.48% ± 1.71% (the NSPCs injection into the hydrogel) and 36.49% ± 4.20% (the hydrogel rehydration in the NSPCs suspension); in control cultures, the level of differentiation in neurons was only 2.40% ± 0.31%. Differentiation of NSPCs into glial cells, in particular into oligodendrocyte progenitor cells, was also observed – 8.89% ± 2.15% and 6.21% ± 0.80% for injection and rehydration variants, respectively; in control – 28.75% ± 2.08%. In the control NSPCs culture, there was a small number of astrocytes – 2.11% ± 0.43%. Inside the hydrogel, NSPCs differentiation in astrocytes was not observed. In vitro data showed that the hydrogel promotes the differentiation of NSPCs into neurons, and inhibits the differentiation into glial cells. And in vivo showed post-traumatic recovery of rat spinal cord tissue after injury followed by implantation of the hydrogel+NSPCs complex (approximately 7 months after SCI). The implant area was closely connected with the recipient tissue, and the recipient cells freely grew into the implant itself. Inside the implant, a formed dense neuronal network was visible. In summary, the results are primarily an experimental ground for further studies of implants based on pHPMA hydrogel with populated different origin SCs, and the data also indicate the feasibility and efficiency of using an integrated approach to reduce possible negative side effects and facilitate the rehabilitation process after a SCI.

An injectable, self-healing, electroconductive hydrogel loaded with neural stem cells and donepezil for enhancing local therapy effect of spinal cord injury

BackgroundSpinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy.MethodsIn this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury.ResultsThe NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction.ConclusionsThe DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

Models of Telehealth Service Delivery in Adults With Spinal Cord Injuries: Scoping Review

Background In Canada, approximately 86,000 people live with spinal cord injury (SCI), and there are an estimated 3675 new cases of traumatic or nontraumatic etiology per year. Most people with SCI will experience secondary health complications, such as urinary and bowel issues, pain syndrome, pressure ulcers, and psychological disorders, resulting in severe chronic multimorbidity. Moreover, people with SCI may face barriers in accessing health care services, such as primary care physicians’ expert knowledge regarding secondary complications related to SCI. Telehealth, defined as the delivery of information and health-related services through telecommunication technologies, may help address some of the barriers, and indeed, the present global COVID-19 pandemic has emphasized the importance of integration of telehealth in health care systems. As a result of this crisis, health care providers have increased the usage of telehealth services, providing health services to individuals in need of community-based supportive care. However, the evidence on models of telehealth service delivery for adults with SCI has not been previously synthesized. Objective The purpose of this scoping review was to identify, describe, and compare models of telehealth services for community-dwelling adults with SCI. Methods This scoping review follows the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Studies published between 1990 and December 31, 2022, were identified by searching the Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of Science, and CINAHL databases. Papers with specified inclusion criteria were screened by 2 investigators. Included articles focused on identifying, implementing, or evaluating telehealth interventions, including primary health care services and self-management services delivered in the community and home-based settings. One investigator performed a full-text review of each article, and data extraction included (1) study characteristics; (2) participant characteristics; (3) key characteristics of the interventions, programs, and services; and (4) outcome measures and results. Results A total of 61 articles reported telehealth services used for preventing, managing, or treating the most common secondary complications and consequences of SCI, including chronic pain, low physical activity, pressure ulcers, and psychosocial dysfunction. Where evidence exists, improvements in community participation, physical activity, and reduction in chronic pain, pressure ulcers, etc, following SCI were demonstrated. Conclusions Telehealth may offer an efficient and effective option for health service delivery for community-dwelling individuals with SCI, ensuring continuity of rehabilitation, follow-up after hospital discharge, and early detection, management, or treatment of potential secondary complications following SCI. We recommend that the stakeholders involved with patients with SCI consider the uptake of hybridized (blend of web-based and in-person) health care delivery models to optimize the care continuum and self-management of SCI-related care. The findings of this scoping review may be used to inform policy makers, health care professionals, and stakeholders engaged in establishing web-based clinics for individuals with SCI.