Post-traumatic Spinal Cord Injury Research Articles

Development and psychometric properties of appraisals of post traumatic spinal cord injury health scale in Iran.

Development and psychometrics study OBJECTIVE: To evaluate the reliability and validity of a new version of Appraisals of Post-Traumatic Spinal Cord Injury Health Scale (APTSCIHS) in the Persian language for persons with spinal cord injury (SCI). The persons were selected from National Spinal Cord Injury Registry of Iran (NSCIR-IR) and Brain and Spinal Cord Injury Research center (BASIR). This was a mixed sequential exploratory study that performed in two phases. In the qualitative phase, a systematic scoping review and 12 interviews with the participants were done. Finally, items were generated. In the quantitative phase, face, content, construct and convergent validity were assessed to evaluate validity. To evaluate construct validity, a cross-sectional study was conducted on 305 persons with TSCI along with internal consistency and stability assessments. All quantitative data analyses were conducted using SPSS 22 software. The content validity and reliability were indicated by Scale's Content Validity Ratio (S-CVR) = 0.73 and Scale's Content Validity Index (S-CVI) = 0.86, Cronbach's α = 0.9 and the Test re-test reliability using intra-class correlations were (ICC) = 0.97 to 0.98. Exploratory factor analysis determined eight factors which showed more than 52% of the variance. APTSCIHS had a significant and strong correlation with Appraisals of DisAbility Primary and Secondary Scale (ADAPSS) (r = 0.475, P < 0.001). Results showed the 36 items APTSCIHS tool had an acceptable validity and reliability in Iran, and it can help health care providers or even administrators improve the quality of the rehabilitation services and quality of life.

Psychosocial reintegration post-traumatic spinal cord injury in Rwanda: An exploratory study.

Traumatic spinal cord injury (TSCI) survivors are confronted by both physical and psychosocial barriers when returning to their communities. Therefore, reintegration is an important aspect of their journey back into social life. To assess psychosocial reintegration after TSCI in Rwanda. All community-dwelling adults who were registered in the previous epidemiological study were recruited and injury characteristics questionnaire and the Sydney Psychosocial Reintegration Scale version 2 (SPRS-2) were used to collect data through a telephone interview. The study traced 58 participants, 77.6% (n = 45) were male and 56.9% (n = 33) were categorised with paraplegia. Overall, the results show poor community reintegration. The SPRS-2 and domain mean (SD) scores were: overall SPRS-2 of 20.95 (11.56), occupational activity (OA) of 3.68 (4.31), interpersonal relationship (IR) of 7.11(4.31) and living skills (LS) of 7.43 (5.32). Gender significantly influenced overall SPRS-2 (p = 0.011) and two domains: OA (p = 0.005) and LS (p = 0.012). Level of injury was significantly associated with an OA domain score of SPRS-2 (p = 0.002). Gender explained 29% of the variance in the LS domain of SPRS-2, with males reporting better psychosocial reintegration. Gender strongly predicted psychosocial reintegration following a TSCI, which is an indication of the role of social support. Traumatic SCI rehabilitation should be holistic to help prepare the person to return to the community. There should be an assessment of an individual's readiness to return to the community before discharge from the hospital.

An Insight into the Prospects and Drawbacks of Stem Cell Therapy for Spinal Cord Injuries: Ongoing Trials and Future Directions.

Spinal cord injury (SCI) is a devastating neurological disorder that has a substantial detrimental impact on a person's quality of life. The estimated global incidence of SCI is 40 to 80 cases per million people and around 90% of cases are traumatic. Various etiologies can be recognized for SCI, and post-traumatic SCI represents the most common of these. Patients worldwide with SCI suffer from a persistent loss of motor and sensory function, which affects every aspect of their personal and social lives. Given the lack of effective treatments, many efforts have been made to seek a cure for this condition. In recent years, thanks to their ability to regenerate tissue and repair lost or damaged cells, much attention has been directed toward the use of stem cells (embryonic, induced pluripotent, mesenchymal, hematopoietic), aimed at restoring the functional integrity of the damaged spinal cord and improving a functional recovery including sensory and motor function. In this paper, we offer an overview of the benefits and drawbacks of stem cell therapy for SCI based on clinical evidence. This report also addresses the characteristics of various stem cell treatments, as well as the field's likely future. Each cell type targets specific pathological characteristics associated with SCI and demonstrates therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation pathways. SCI accompanied by complex pathological processes cannot be resolved by single treatment measures. Stem cells are associated with the adjustment of the expression of neurotrophic factors that help to achieve better nutrition to damaged tissue. Single-cell treatments have been shown in some studies to provide very minor benefits for SCI in multiple preclinical studies and a growing number of clinical trials. However, SCI damage is complex, and many studies are increasingly recognizing a combination approach such as physical therapy, electrical stimulation, or medication therapy to treatment.

The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 μL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Exploring Loneliness in the Spinal Cord Injury & You Study Participants

<h3>Research Objectives</h3> Loneliness is emerging as a fundamental risk factor for poorer health outcomes. Little is known about loneliness in the US spinal cord injury (SCI) population. The SCI&U intervention occurred entirely during the global COVID-19 pandemic, affording an opportunity to assess prevalence of loneliness among participants. SCI&U is a virtual health self-management program utilizing the Peer Health Coaching (PHC) model to support health, well-being, and enhanced quality of life for community-dwelling individuals living with SCI. <h3>Design</h3> PHCs are experienced peer mentors with SCI, trained to coach others with SCI. PHCs used smartphones and an online platform, combining videoconferencing with an SCI health resource library, specified talking points, and conversation flow charts. <h3>Setting</h3> Community dwellings. <h3>Participants</h3> 23 adults, 1-23 years post-traumatic SCI. <h3>Interventions</h3> PHCs completed up to 14 coaching calls during 30-45-minute-long scheduled sessions with participants, supporting them as they addressed issues related to their health. Participants completed assessments through the secure SCI&U platform. <h3>Main Outcome Measures</h3> Participants completed baseline assessments prior to the intervention, including the NIH Toolbox Loneliness Survey, which has high construct validity. <h3>Results</h3> 17 of the 23 participants scored 60+ points, suggesting a high-level of loneliness. 3 participants scored < 40, which suggests a low-level of loneliness, and the remaining 3 participants scored between 40 and 60 points, an average range of self-reported loneliness. <h3>Conclusions</h3> Limitations include the small sample size, the measure's lack of predictive and concurrent validity, and of clinically meaningful thresholds. High scores of the majority may warrant heightened surveillance or concern, particularly considering COVID. Virtual coaching by a PHC is a viable form of support to address health-related issues and factors that impact loneliness for people with SCI who may be isolated due to COVID, or other ongoing barriers. <h3>Author(s) Disclosures</h3> The authors do not have any conflicts to disclose.

Spinal Cord Injury & You Study Participants Health Education Impact Questionaire Scores

<h3>Research Objectives</h3> To explore how SCI&U study participants rated satisfaction, acceptability, and relevance post-intervention. SCI&U is a virtual health self-management program that utilizes the Peer Health Coaching model to support health, well-being, and enhanced quality of life for those living with spinal cord injury (SCI). <h3>Design</h3> The SCI-Peer Health Coach (PHC) plays a powerful role in promoting health-management among community-dwelling adults with spinal cord injury. PHCs are experienced peer mentors with SCI who are specifically trained to coach others with SCI. <h3>Setting</h3> PHCs used an online platform combining videoconferencing with an SCI health resource library, talking points, and conversation flow charts. Coaching also occurred using smart phones. <h3>Participants</h3> 8 community-dwelling adults 1- 23 years post-traumatic SCI. <h3>Interventions</h3> Person-centered coaching supported participants with identifying and managing barriers related to any health issue they wanted to address. PHCs completed up to 14 coaching calls during 30-45-minute-long scheduled coaching sessions with participants for up to 5 months. PHCs tracked the progress of their peers in setting and reaching their goals on a password protected portal. Peers completed assessments through the secure SCI&U platform post-intervention. <h3>Main Outcome Measures</h3> Participants rated satisfaction, acceptability, and relevance post-intervention using the Health Education Impact Questionnaire (heiQ) measure, which has high construct validity and is a reliable measure of a broad range of patient education program benefits for chronic condition management. <h3>Results</h3> heiQ mean scores averaged 3.7/4 for goal setting, information sharing, relevance, feeling validated, and the coaching relationship. <h3>Conclusions</h3> The SCI&U program was highly valued by program participants. Virtual coaching provided by a PHC is a viable role for future programs that aim to support addressing health needs and increasing the quality of life for the SCI community. <h3>Author(s) Disclosures</h3> The authors do not have any conflicts to declare.

Treatments perceived to be helpful for neuropathic pain after traumatic spinal cord injury: A multicenter cross-sectional survey study

Design Cross-sectional survey. Objective To evaluate the perceived helpfulness of pharmacological and non-pharmacological interventions and their combinations for neuropathic pain (NeuP) and subcategories of NeuP after spinal cord injury (SCI). Setting Six Spinal Cord Injury Model System Centers. Methods Three hundred ninety one individuals at least one year post traumatic SCI were enrolled. A telephone survey was conducted to determine the pharmacologic and non-pharmacologic treatments used in the last 12 months for each participant’s three worst pains, whether these treatments were “helpful”, and if currently used, each treatments’ effectiveness. Results Two hundred twenty participants (56%) reported 354 distinct NeuPs. Pharmacological treatments rated helpful for NeuP were non-tramadol opioids (opioids were helpful for 86% of opioid treated NeuPs), cannabinoids (83%), and anti-epileptics (79%). Non-pharmacological treatments rated helpful for NeuP were massage (76%), body position adjustment (74%), and relaxation therapy (70%). Those who used both opioids and exercise reported greater NeuP treatment helpfulness compared to participants using opioids without exercise (P = 0.03). Conclusions Opioids, cannabinoids, and massage were reported more commonly as helpful than treatments recommended as first-line therapies by current clinical practice guidelines (CPGs) for NeuP after SCI (antiepileptics and antidepressants). Individuals with SCI likely value the modulating effects of pharmacological and non-pharmacological treatments on the affective components of pain in addition to the sensory components of pain when appraising treatment helpfulness.

Study on the role of epidural steroids in various spine problems

Background and Aim: The majority of chronic pain patients suffer from pain emanating from the spine and adjacent structures. Spasticity has the potential to negatively influence quality of life (QOL) through restricting activities of daily living. Hence the aim of present study were to study the efficacy of epidural steroid injection in pain control and to study the role of epidural steroid in reduction of spasticity in post traumatic spasticity in spinal cord injury patients. Materials &amp; Methods: A total of 230 patients attending our hospital for a period of three years were evaluated and followed up. Of the total included patients, 200 patients were having either back pain, sciatica, neck pain with or without radiculopathy and 30 patients were having post traumatic spinal cord injury with spasticity. All the patients were assessed for spasticity according to modified Ashworth scale. All the patients were given epidural steroid at regular interval of 21 days at paraplegia clinic.

The method of quantitative assessment of posttraumatic spinal cord injury volume and structure in animal models using magnetic resonance tomography

Introduction. Spinal cord injury is a debilitating traumatic event in central nervous system resulting in tissue destruction and severe neurological deficit development. Preclinical assessment of quantitative lesion area parameters (e. g. structure and volume) is critical for subsequent evaluation of neuroprotective and / or neuroregenerative therapy efficiency. Current methods for parameter calculation require manual limitation of the interested area (region of interest, RoI). This process is tedious and often not precise enough.Study objective is to develop and implement software for automated assessment of volume and structure of posttraumatic spinal cord lesion using extra-high-field MRI 7.0 Tesla and to compare methods preciseness with the current manual techniques.Study design. Ten rat models of acute severe spinal cord contusion injury were used including female Sprague–Dawley animals weighting 250–350 gr. MRI imaging was performed in 1 day postoperative and then 4 times with interval (1 week). Study was prospective open-label uncontrolled comparative.Materials and methods. Standard spinal cord contusion injury model was used. Anesthetized animals underwent laminectomy at level Th9–Th10 vertebrae followed by “weight drop” injury technique application: 10 g weight with 2 mm pin diameter dropped from 25 mm height. Software was developed using Microsoft Visual Studio 2017 environment and programming language C#. Statistical analysis was performed using IBM SPSS Statistics 21.0 software.Results. We developed and patented specialized software Spinal cavity Searcher realizing the algorithm of T2‑weighted images (T2‑WI) analysis based on image bynarization and Freeman chain code. This algorithm supports calculation of spinal cord posttraumatic lesion parameters in a half-automatic manner. Results of this algorithm application were comparable to results of manual calculation: no statistical difference were observed between two values.Conclusion. Current method of spinal cord injury volume and structure quantitative assessment simplifies the calculation procedure due to automatization of RoI limitation comparing to manual technique. The level of preciseness is comparable in both methods.Clinical relevance. The developed algorithm optimizes the process of non-invasive control of the performed treatment efficiency according to 7.0 Tesla MRI data.

The relationship between health behaviors and emergency department visits and hospitalizations after traumatic spinal cord injury.

Cross-sectional study. To identify demographic, injury, and behavioral predictors of emergency department (ED) visits and ED-related hospitalizations among individuals with chronic traumatic spinal cord injury (SCI). An academic medical center in the Southeastern United States. 4057 participants who were at least 18 years of age and 1 year post traumatic SCI with residual neurologic impairment were identified from three cohorts: a rehabilitation specialty hospital in the Southeastern USA and two SCI Surveillance System Registries, one in the Midwestern and one in the Southeastern USA. The participants completed a self-reported assessment on ED visits and ED hospitalizations (yes/no) in the past 12 months. Logistic regression models were used to examine the relationship between ED visits/hospitalizations and eight behavioral indicators, including body weight, healthy diet, drinking, smoking, non-medical substance usage, prescription medication usage, prescription medication misuse, and the planned exercise. During the study period, 41% of participants reported having at least one ED visit and 21% participants reported hospitalization after ED visit in the past 12 months. High frequency of prescription medication usage, prescription medication misuse, and lack of planned exercise were associated with greater odds of at least one ED visit and at least one ED-related hospitalization, while smoking was only associated with ED visits. Health care professionals should be aware that ED visit and related hospitalization prevalence remain high among people with chronic SCI, and there is significant need for intervention of managing risk behaviors and promoting healthy behaviors after SCI.

Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.

Excessive inflammation post-traumatic spinal cord injury (SCI) induces microglial activation, which leads to prolonged neurological dysfunction. However, the mechanism underlying microglial activation-induced neuroinflammation remains poorly understood. Ruxolitinib (RUX), a selective inhibitor of JAK1/2, was recently reported to inhibit inflammatory storms caused by SARS-CoV-2 in the lung. However, its role in disrupting inflammation post-SCI has not been confirmed. In this study, microglia were treated with RUX for 24 hours and then activated with interferon-γ for 6 hours. The results showed that interferon-γ-induced phosphorylation of JAK and STAT in microglia was inhibited, and the mRNA expression levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and cell proliferation marker Ki67 were reduced. In further in vivo experiments, a mouse model of spinal cord injury was treated intragastrically with RUX for 3 successive days, and the findings suggest that RUX can inhibit microglial proliferation by inhibiting the interferon-γ/JAK/STAT pathway. Moreover, microglia treated with RUX centripetally migrated toward injured foci, remaining limited and compacted within the glial scar, which resulted in axon preservation and less demyelination. Moreover, the protein expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were reduced. The neuromotor function of SCI mice also recovered. These findings suggest that RUX can inhibit neuroinflammation through inhibiting the interferon-γ/JAK/STAT pathway, thereby reducing secondary injury after SCI and producing neuroprotective effects.

Fetal and Perinatal Expression Profiles of Proinflammatory Cytokines in the Neuroplacodes of Rats with Myelomeningoceles: A Contribution to the Understanding of Secondary Spinal Cord Injury in Open Spinal Dysraphism.

The cellular and molecular mechanisms that presumably underlie the progressive functional decline of the myelomeningocele (MMC) placode are not well understood. We previously identified key players in post-traumatic spinal cord injury cascades in human MMC tissues obtained during postnatal repair. In this study, we conducted experiments to further investigate these mediators in the prenatal time course under standardized conditions in a retinoic acid-induced MMC rat model. A retinoic acid MMC model was established using time-dated Sprague-Dawley rats, which were gavage-fed with all-trans retinoic acid (RA; 60 mg/kg) dissolved in olive oil at E10. Control animals received olive oil only. Fetuses from both groups were obtained at E16, E18, and E22. The spinal cords (SCs) of both groups were formalin-fixed or snap-frozen. Tissues were screened by real-time reverse transcription polymerase chain reaction for the expression of cytokines and chemokines known to play a role in the lesion cascades of the central nervous system after trauma. MMC placodes exhibited inflammatory cells and glial activation in the later gestational stages. At the messenger RNA (mRNA) level, interleukin-1 beta, tumor necrosis factor alpha, and tumor necrosis factor receptor type 1 exhibited significant induction at E22. interleukin-1 beta receptor type 1 mRNA was induced significantly at E16 and E22. Double labeling experiments confirmed the co-staining of these cytokines and their receptors with ionized calcium-binding adapter molecule 1 (i.e., inflammatory cells), vimentin, and nestin in different anatomical SC areas and neuronal nuclear protein in ventral horn neurons. C-X-C motif chemokine 12 mRNA was elevated in control and MMC animals at E16 compared with E18 and E22. C-X3-C motif ligand 1 mRNA was lower in MMC tissues than in control tissues on E16. The presented findings contribute to the concept that pathophysiological mechanisms, such as cytokine induction in the neuroplacode, in addition to the "first hit," promote secondary spinal cord injury with functional loss in the late fetal time course. Further, these mediators should be taken into consideration in the development of new therapeutic approaches for open spinal dysraphism.

Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input–output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

Treatments that are perceived to be helpful for non-neuropathic pain after traumatic spinal cord injury: a multicenter cross-sectional survey.

Cross-sectional survey. The objective of the study was to identify the treatments that people with traumatic spinal cord injury (SCI) used for their non-neuropathic pains (nonNeuPs) and how they subjectively rated the helpfulness of those treatments. Six centers from the Spinal Cord Injury Model Systems. Three hundred ninety one individuals who were at least 1-year post-traumatic SCI were enrolled. A telephone survey was conducted for pharmacologic and non-pharmacologic treatments utilized in the last 12 months for each participant's three worst pains and the perceived helpfulness of each treatment for each pain. One hundred ninety (49%) participants reported at least one nonNeuP (Spinal Cord Injury Pain Instrument score < 2) in the previous 7 days. NSAIDs/aspirin, acetaminophen, opioids, and cannabinoids were the most commonly used and helpful pharmacologic treatments for overall nonNeuP locations (helpful in 77-89% of treated pains). Body position adjustment, passive exercise, massage, resistive exercise, and heat therapy were reported as the most commonly used non-pharmacological treatments for nonNeuPs. Heat therapy, aerobic exercise, massage, and body position adjustment were the most helpful non-pharmacological treatments for overall nonNeuP locations (helpful in 71-80% of treated pains). Perceived helpfulness of treatments varied by pain locations, which may be due to different mechanisms underlying pains in different locations. Results of the study may help guide clinicians in selecting pain-specific treatments for nonNeuPs. The self-reported helpfulness of heat therapy, exercise, and massage suggests a possible direction for clinical trials investigating these treatments of nonNeuP while limiting the side effects accompanying pharmacologic treatments.

Body experience during post-acute rehabilitation in individuals after a traumatic spinal cord injury: a qualitative interview-based pilot study

Study designQualitative interview-based pilot study.ObjectivesA traumatic spinal cord injury (TSCI) profoundly disrupts the way individuals experience their body. Awareness of one’s body is an important element in the psychological adjustment process after TSCI. This pilot study aimed to explore the body experience of individuals during post-acute rehabilitation following TSCI.SettingSpecialized acute care and rehabilitation center in Switzerland.MethodsEight semi-structured face-to-face interviews were conducted with patients in the post-acute phase of their TSCI. Body experience was explored in relation to perceptive, cognitive, emotional, and behavioral aspects. The interviews were transcribed verbatim, and a structured content analysis was performed according to the Mayring method.ResultsThe individuals verbalized body experience in all explored aspects. The two participants with tetraplegia described high body-related awareness, including dependence on other persons or aids, whereas individuals with paraplegia focused on their ability to regain activity and perceived autonomy, which was sustained by increasing injury- and self-related comprehension. They expressed uncertainty in their understanding of their paralyzed body while also verbalizing to see a continuity in their identity pre and post TSCI. Their emotions varied from anxiety and anger to hope and optimism. The interviewees confirmed that the growing ability to describe perceptions related to their body increased their active participation in the rehabilitation process and stimulated hope for the future.ConclusionsExploration of individual body experience after a recent TSCI can strengthen patients’ body awareness, communication and engagement in rehabilitation and help the interprofessional rehabilitation team individualize the rehabilitation process.

Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury

BackgroundThe pathological process of traumatic spinal cord injury (SCI) involves excessive activation of microglia leading to the overproduction of proinflammatory cytokines and causing neuronal injury. Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in mediating inflammation, cell proliferation, survival, and immunity.MethodsWe aim to investigate the mechanism and pathway of the Sphk1-mediated neuroinflammatory response in a rodent model of SCI. Sixty Sprague-Dawley rats were randomly assigned to sham surgery, SCI, or PF543 (a specific Sphk1 inhibitor) groups. Functional outcomes included blinded hindlimb locomotor rating and inclined plane test.ResultsWe discovered that Sphk1 is upregulated in injured spinal cord tissue of rats after SCI and is associated with production of S1P and subsequent NF-κB p65 activation. PF543 attenuated p65 activation, reduced inflammatory response, and relieved neuronal damage, leading to improved functional recovery. Western blot analysis confirmed that expression of S1P receptor 3 (S1PR3) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) are activated in microglia of SCI rats and mitigated by PF543. In vitro, we demonstrated that Bay11-7085 suppressed NF-κB p65 and inhibited amplification of the inflammation cascade by S1P, reducing the release of proinflammatory TNF-α. We further confirmed that phosphorylation of p38 MAPK and activation of NF-κB p65 is inhibited by PF543 and CAY10444. p38 MAPK phosphorylation and NF-κB p65 activation were enhanced by exogenous S1P and inhibited by the specific inhibitor SB204580, ultimately indicating that the S1P/S1PR3/p38 MAPK pathway contributes to the NF-κB p65 inflammatory response.ConclusionOur results demonstrate a critical role of Sphk1 in the post-traumatic SCI inflammatory cascade and present the Sphk1/S1P/S1PR3 axis as a potential target for therapeutic intervention to control neuroinflammation, relieve neuronal damage, and improve functional outcomes in SCI.

Very complex and difficult rehabilitation process in a post traumatic SCI (Spinal Cord Injury) complete tetraplegic patient with intense and refractory spasticity and frequency of spasm with presacral pressure sores (successfully operated)- case report

Introduction. Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion.(1) As a result of the injury, the functions performed by the spinal cord are interrupted at the distal level of the injury. SCI causes serious disability among patients.(2) The treatment and rehabilitation period is long, expensive and exhausting in SCI. The results of SCI bring not only damage to independence and physical function, but also include many complications from the injury. Neurogenic bladder and bowel, urinary tract infections, pressure ulcers, orthostatic hypotension, fractures, deep vein thrombosis, spasticity, autonomic dysreflexia, pulmonary and cardiovascular problems, and depressive disorders are frequent complications after SCI.(3) Material and method. Having the patient’s consent and The Teaching Emergency Hospital “Bagdasar-Arseni” Ethics Committee’s approval, a 48 years old patient, complete tetraplegic with intense and refractory spasticity and frequency of spasm with presacral pressure sores (successfully operated) post traumatic spinal cord injury. The patient was functionally assessed using the following scales: : Glasgow Outcome Scale Extended, Modified Rankin Scale, Modified Ashworth, Penn Spasm Frequency Scale Functional Independence Measure, FAC International Scale, Quality of Life Assessment. Conclusions. Spasticity is a common secondary impairment after SCI characterized by hypertonus, increased intermittent or sustained involuntary somatic reflexes (hyperreflexia), clonus and painful muscle spasms. Severe spasticity may contribute to increased functional impairment, contractures, ulcers, posture disorders and pain. Treatment should start as soon as possible to prevent such negative effects. Keywords: tetraplegia, spinal cord injury, spasticity, pressure sores, traumatism, rehabilitation,

7.0 Tesla High-Field MRI for Quantitative Assessment of Posttraumatic Spinal Cord Injury Area Volume in Animal Models

Spinal cord injury is a complex dynamic process occurring after mechanical damage of the spinal cord and followed by a series...

MRI in Acute Post-Traumatic Spinal Cord Injury: Assessment of MRI Findings in Predicting Prognosis

MRI in Acute Post-Traumatic Spinal Cord Injury: Assessment of MRI Findings in Predicting Prognosis

Oral treatment with glycyrrhizin inhibits NLRP3 inflammasome activation and promotes microglial M2 polarization after traumatic spinal cord injury

The inflammatory response induced by traumatic spinal cord injury (SCI) involves the activation of NLRP3 inflammasomes, which are closely related to the activation of microglia. Microglial polarization between M1/M2 phenotypes is a pivotal regulatory factor in neuroinflammatory responses to traumatic SCI-induced secondary injuries, and altering this polarization could be beneficial. Glycyrrhizin is a neuroprotective agent with a potent anti-inflammatory property in different neurological disorders and could potentially be useful in SCI. In this study, we investigated the potency of oral treatment with glycyrrhizin to reduce inflammation and improve functional recovery after traumatic SCI by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization. After inducing traumatic SCI by dropping a 10 g impactor on the T9 and T10 spinal segments of male Sprague-Dawley rats, the animals were given glycyrrhizin orally immediately after injury and every 12 h for the next 3 d. Behavioral scores improved in glycyrrhizin-treated animals compared to the SCI group. The functional improvement in glycyrrhizin-treated rats paralleled the decreased expression of NLRP3 inflammasome components, such as ASC, NLRP3, and cleaved caspase-1, as well as IL-1β and IL-18. At the histopathological level, oral treatment with glycyrrhizin diminished the SCI-enhanced production of Iba-1+CD86+ cells (M1 microglia) but improved the release of Iba-1+CD206+ cells (M2 microglia). Likewise, oral therapy with glycyrrhizin significantly enriched the protein expression levels of M2 microglia-related markers (CD206 and Arg-1) but reduced those of M1 microglia-related markers (CD86 and iNOS) in the injured spinal cord. These findings support and extend the knowledge on post-traumatic SCI glycyrrhizin-mediated neuroprotection. Glycyrrhizin’s regulation of NLRP3 inflammasome activation and microglial polarization might be a new approach to understanding the anti-inflammatory potency of glycyrrhizin.