Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) attenuate inflammatory responses in the central nervous system, leading to neuroprotective effects. Inhibition of histone deacetylase 3 (HDAC3) has neuroprotective effects after spinal cord injury (SCI) through the SIRT1 pathway, but the pathophysiological mechanisms of SCI are complex and the interactions between ω-3 PUFAs and organelles remain largely unknown. This study aimed to investigate the effect of ω-3 PUFAs on endoplasmic reticulum (ER) stress-induced neuroinflammation through the HDAC3/peroxisome proliferator-activated receptor-γ coactivator (PGC)-1ɑ pathway after SCI. To this end, a contusion-induced SCI rat model was established to evaluate the effects of ω-3 PUFAs on ER stress-mediated inflammation in SCI. ER stress was rapidly induced in spinal cord lesions after SCI and was significantly reduced after ω-3 PUFA treatment. Consistent with reduced ER stress, HDAC3 expression levels and inflammatory responses were decreased, and PGC-1ɑ expression levels were increased after SCI. We found that ω-3 PUFA treatment attenuated ER stress through HDAC3 inhibition, thereby reducing SCI-induced inflammation. Taken together, these results suggest a role for ω-3 PUFA in protecting against SCI-induced neuroinflammation and promoting neurological functional recovery by regulating the histone deacetylase 3/ peroxisome proliferator-activated receptor-γ coactivator pathway.

METHODS: We conducted a retrospective, descriptive register study.
OBJECTIVE: The aim of the study was to present the epidemiological and demographic characteristics of the Swedish spinal cord injury (SCI) population.
METHODS: Rehabilitation units in Sweden were connected to the National Quality Register for Rehabilitation Medicine (Svenskt Register för Rehabiliteringsmedicin: SveReh). The registry includes data from 26 units around the country.
METHODS: Information was extracted from SveReh for patients who underwent rehabilitation for a new onset SCI between January 1, 2016, and December 31, 2020. Data regarding gender, age, aetiology, level of injury, neurogenic bowel and/or bladder dysfunction, complications during the primary rehabilitation, and the need for bi-level positive airway pressure, continuous positive airway pressure, or ventilator were analysed.
RESULTS: Mean age at onset was 56 years, and men were overrepresented (66%). Tetraplegia was more common among traumatic SCI (TSCI) than non-traumatic SCI (NTSCI). The incidence was 11.9-14.8 per million for TSCI and 8.9-11.8 per million for NTSCI. At discharge, 8% of patients needed a breathing aid. Of those who were ventilator-dependent at discharge, 75% had a TSCI. Disturbed bowel and bladder functioning was noted in 58% of patients at discharge. The median time spent at the unit was 40 days, but it was approximately 2 weeks longer for those with a TSCI.
CONCLUSIONS: Systematic and updated data on the Swedish SCI population show a pattern similar to Scandinavian countries with high age at onset and falls being the main cause of TSCI. The TSCI incidence was lower than in previous studies, and the results for NTSCI were novel.

OBJECTIVE: We aimed to explore the prognostic significance of preoperative magnetic resonance imaging (MRI) variables and novel inflammatory indicators in predicting neurological recovery post-cervical traumatic spinal cord injury (TSCI) in the study.
METHODS: We enrolled a total of 244 patients diagnosed with acute cervical TSCI from 2 hospitals and evaluated the prognostic value of MRI variables (intramedullary hemorrhage, intramedullary lesion length [IMLL], maximum spinal cord compression, and maximum canal compromise [MCC]) and novel inflammatory indicators (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune-inflammatory index) in patients with acute cervical TSCI.
RESULTS: Among the 244 patients, 140 (57.38%) exhibited improved AIS grade conversion at 1-year follow-up. The results revealed intramedullary hemorrhage, IMLL, MCC, neutrophils, and NLR were significantly different compared with follow-up AIS grade. Furthermore, IMLL, MCC, white blood cells, neutrophils, NLR, and lymphocyte-to-monocyte ratio correlated with the follow-up AIS grade by Spearman\'s correlation analysis. Multivariate analysis showed IMLL, intramedullary hemorrhage, NLR, and admission AIS grade emerged as independent predictors of AIS grade conversion. The receiver operating characteristic curve analysis showed that the novel model (combination of MRI variables, NLR, and admission AIS grade) produced a larger area under the curve compared with using only intramedullary hemorrhage, IMLL, NLR, or admission AIS grade individually.
CONCLUSIONS: Intramedullary hemorrhage and IMLL and NLR are predictors of AIS grade conversion after cervical TSCI. Therefore, we suggest the combination of MRI variables and NLR for the prognostic prediction of AIS grade conversion in patients with cervical TSCI.

UNASSIGNED: The study of epidemiological changes of traumatic spinal cord injury (TSCI) is needed due to its highly variable incidence.
UNASSIGNED: To determine the incidence of TSCI in Spain and to describe the trend of clinical and demographic characteristics according to age group during a 10-year period.
UNASSIGNED: A prospective cohort study was conducted. A multidisciplinary team evaluated all individuals with new TSCI. The data were recorded according to the International Spinal Cord Injury Core Data Sets.
UNASSIGNED: In a 10-year period, 933 new patients with TSCI were admitted to the hospital. The annual incidence of TSCI was 6.2 per million. The leading causes of injury were traffic accidents (38.5%), low-level falls (20.6%), and high-level falls (19.1%). Males, age group of 31-45 years, and cervical level of injury were the most common profiles of TSCI. In patients over 60 years,71.5% were injured following a fall, particularly low-level falls (47.2%). In patients under 60 years old, the leading cause of SCI was traffic accidents (46%). The proportion of tetraplegia in patients above 60 years was 68.3%, compared to 43.7% in patients under 60 years of age. Patients in the age group above 60 years were hospitalized with a shorter duration of rehabilitation compared to younger age group.
UNASSIGNED: Compared with globally estimated data reported in previous studies, this research demonstrated a low incidence of TSCI in Spain, suggesting a decrease in the last years. Falls and traffic accidents were the most common causes of TSCI in elderly and youth, respectively. Prevention programs should focus on these issues.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.

UNASSIGNED: Chronic pain among survivors of spinal cord injury (SCI) hurts physical and mental health. Persons with SCI have demonstrated dissatisfaction with the management of their chronic pain.
UNASSIGNED: This study aimed to identify existing clinical practice guidelines for chronic pain in the SCI population.
UNASSIGNED: A scoping review was conducted across various databases available at the University of the Western Cape, in addition to guideline clearing houses (BioMedCentral, Cambridge Journals Online, CINAHL, Cochrane Library, Medline [EbscoHost], Medline [Pubmed], Sabinet Reference, SAGE Journals Online, ScienceDirect, SCOPUS, Wiley Online Library, Springerlink, PubMed, Guideline Central, and Agency for Healthcare Research and Quality). The population consisted of adults with SCI, and the interventions that were included were pharmacological and nonpharmacological management of chronic pain. Guidelines that met the inclusion criteria were critically appraised by two reviewers from this study using the AGREE II instrument. Inter-rater reliability was calculated using SPSS 27, and Cohen\'s kappa coefficients were established.
UNASSIGNED: Five articles were included in the data extraction, analysis and appraisal. Two guidelines were rated as high quality, according to the AGREE II tool. In addition, most guidelines focused on neuropathic pain (NeuP) and only one guideline included nociceptive pain and NeuP.
UNASSIGNED: One guideline met the objectives of this scoping review.
UNASSIGNED: Guidelines developed in the future should include a screening tool to identify the specific type of pain and distinguish peripheral NeuP from central NeuP.

Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field.

UNASSIGNED: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI.
UNASSIGNED: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI?
UNASSIGNED: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry.
UNASSIGNED: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections.
UNASSIGNED: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI.