Pathophysiology Of Spinal Cord Injury Research Articles

The feasibility of acupuncture on post-spinal cord injury treatment

Spinal cord injury (SCI) simultaneously causes multiple and interrelated pathophysiological disorders throughout the nervous system, hindering the development of effective treatment strategies. Mechanistically, SCI triggers excitatory signaling activation, downregulation of the inhibitory system, neuronal death, followed by the development of new synaptic circuits and reorganization, leading to neurological dysfunctions and mental disorders. Therefore, a simultaneous treatment strategy, known as overlapping treatment, is needed. Over decades, both preclinical and clinical studies have established that acupuncture treatment offers neuroprotection, pain attenuation, improvement of functional recovery, and promotes reward behaviors, suggesting potential roles of acupuncture in post-SCI treatment. Recently, the importance of overlapping treatment has been recognized in developing effective treatments for post-SCI pathophysiology. However, there has been no systematic study investigating the role of acupuncture in various SCI pathophysiology. In this review, we briefly address the mechanisms of post-SCI pathophysiology and discuss the potential therapeutic effects of acupuncture, suggesting its feasibility as a treatment for post-SCI pathophysiology.

The feasibility of acupuncture on post-spinal cord injury treatment

Spinal cord injury (SCI) simultaneously causes multiple and interrelated pathophysiological disorders throughout the nervous system, hindering the development of effective treatment strategies. Mechanistically, SCI triggers excitatory signaling activation, downregulation of the inhibitory system, neuronal death, followed by the development of new synaptic circuits and reorganization, leading to chronic neurological dysfunctions and mental disorders. Therefore, a simultaneous treatment strategy, known as overlapping treatment, is needed. Over decades, both preclinical and clinical studies have established that acupuncture treatment offers neuroprotection, pain attenuation, improvement of functional recovery, and promotes reward behaviors, suggesting potential roles of acupuncture in post-SCI treatment. Recently, the importance of overlapping treatment has been recognized in developing effective treatments for post-SCI pathophysiology. However, there has been no systematic study investigating the role of acupuncture in various SCI pathophysiology. In this review, we briefly address the mechanisms of post-SCI pathophysiology and discuss the potential therapeutic effects of acupuncture, suggesting its feasibility as a treatment for post-SCI pathophysiology.

The role of small extracellular vesicles and microRNA as their cargo in the spinal cord injury pathophysiology and therapy.

Spinal cord injury (SCI) is a devastating condition with a complex pathology that affects a significant portion of the population and causes long-term consequences. After primary injury, an inflammatory cascade of secondary injury occurs, followed by neuronal cell death and glial scar formation. Together with the limited regenerative capacity of the central nervous system, these are the main reasons for the poor prognosis after SCI. Despite recent advances, there is still no effective treatment. Promising therapeutic approaches include stem cells transplantation, which has demonstrated neuroprotective and immunomodulatory effects in SCI. This positive effect is thought to be mediated by small extracellular vesicles (sEVs); membrane-bound nanovesicles involved in intercellular communication through transport of functional proteins and RNA molecules. In this review, we summarize the current knowledge about sEVs and microRNA as their cargo as one of the most promising therapeutic approaches for the treatment of SCI. We provide a comprehensive overview of their role in SCI pathophysiology, neuroprotective potential and therapeutic effect.

Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats.

Inflammatory responses play a crucial role in the pathophysiology of spinal cord injury (SCI) and developing new approaches to establish an anti-inflammatory environment for the promotion of neuroregeneration holds promise as a potential approach. In this study, our aim was to investigate the potential of combining an acellular spinal cord scaffold (ASCS) with quercetin-loaded bovine serum albumin (Qu/BSA) nanoparticles (NPs) for the treatment of SCI. The ASCS was prepared using physical and chemical methods, while the Qu/BSA NPs were prepared through a desolvation technique. The NPs exhibited favorable characteristics, including a mean size of 203nm, a zeta potential of -38, and an encapsulation efficiency of 96%. Microscopic evaluation confirmed the successful distribution of NPs on the walls of ASCS. Animal studies revealed that Qu/BSA NPs group exhibited a significant decrease in NLRP3, ASC, and Casp1 gene expression compared to the SCI group (p < 0.0001). The findings indicated a significant decrease in the NLRP3, ASC, and Casp1 protein level between the Qu/BSA/ASCS group and the SCI group (p < 0.0001). Moreover, treatment with ASCS containing either blank BSA (B/BSA) NPs or Qu/BSA NPs effectively promoted functional recovery via increasing the amount of nestin- and glial fibrillary acidic protein (GFAP)-positive cells in the site of injury. Notably, Qu/BSA/ASCS exhibited superior outcomes compared to B/BSA/ASCS. Overall, the combination of ASCS with the Qu delivery system presents a promising therapeutic approach for SCI by inhibiting inflammatory responses and promoting neuroregeneration, leading to the restoration of motor function in animals. This study demonstrates the potential of utilizing biomaterials and NPs to enhance the effectiveness of SCI treatment.

NF-κB and JAK/STAT Signaling Pathways as Crucial Regulators of Neuroinflammation and Astrocyte Modulation in Spinal Cord Injury.

Spinal cord injury (SCI) leads to significant functional impairments below the level of the injury, and astrocytes play a crucial role in the pathophysiology of SCI. Astrocytes undergo changes and form a glial scar after SCI, which has traditionally been viewed as a barrier to axonal regeneration and functional recovery. Astrocytes activate intracellular signaling pathways, including nuclear factor κB (NF-κB) and Janus kinase-signal transducers and activators of transcription (JAK/STAT), in response to external stimuli. NF-κB and STAT3 are transcription factors that play a pivotal role in initiating gene expression related to astrogliosis. The JAK/STAT signaling pathway is essential for managing secondary damage and facilitating recovery processes post-SCI: inflammation, glial scar formation, and astrocyte survival. NF-κB activation in astrocytes leads to the production of pro-inflammatory factors by astrocytes. NF-κB and STAT3 signaling pathways are interconnected: NF-κB activation in astrocytes leads to the release of interleukin-6 (IL-6), which interacts with the IL-6 receptor and initiates STAT3 activation. By modulating astrocyte responses, these pathways offer promising avenues for enhancing recovery outcomes, illustrating the crucial need for further investigation into their mechanisms and therapeutic applications in SCI treatment.

Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury.

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

Effects of Recombinant IL-13 Treatment on Gut Microbiota Composition and Functional Recovery after Hemisection Spinal Cord Injury in Mice.

In recent years, the gut-central nervous system axis has emerged as a key factor in the pathophysiology of spinal cord injury (SCI). Interleukin-13 (IL-13) has been shown to have anti-inflammatory and neuroprotective effects in SCI. The aim of this study was to investigate the changes in microbiota composition after hemisection injury and to determine whether systemic recombinant (r)IL-13 treatment could alter the gut microbiome, indirectly promoting functional recovery. The gut microbiota composition was determined by 16S rRNA gene sequencing, and correlations between gut microbiota alterations and functional recovery were assessed. Our results showed that there were no changes in alpha diversity between the groups before and after SCI, while PERMANOVA analysis for beta diversity showed significant differences in fecal microbial communities. Phylogenetic classification of bacterial families revealed a lower abundance of the Bacteroidales S24-7 group and a higher abundance of Lachnospiraceae and Lactobacillaceae in the post-SCI group. Systemic rIL-13 treatment improved functional recovery 28 days post-injury and microbiota analysis revealed increased relative abundance of Clostridiales vadin BB60 and Acetitomaculum and decreased Anaeroplasma, Ruminiclostridium_6, and Ruminococcus compared to controls. Functional assessment with PICRUSt showed that genes related to glyoxylate cycle and palmitoleate biosynthesis-I were the predominant signatures in the rIL-13-treated group, whereas sulfolactate degradation super pathway and formaldehyde assimilation-I were enriched in controls. In conclusion, our results indicate that rIL-13 treatment promotes changes in gut microbial communities and may thereby contribute indirectly to the improvement of functional recovery in mice, possibly having important implications for the development of novel treatment options for SCI.

Comparative Analysis of Cytokine Profiles in Cerebrospinal Fluid and Blood Serum in Patients with Acute and Subacute Spinal Cord Injury.

Cytokines are actively involved in the regulation of the inflammatory and immune responses and have crucial importance in the outcome of spinal cord injuries (SCIs). Examining more objective and representative indicators of the patient's condition is still required to reveal the fundamental patterns of the abovementioned posttraumatic processes, including the identification of changes in the expression of cytokines. We performed a dynamic (3, 7, and 14 days post-injury (dpi)) extended multiplex analysis of cytokine profiles in both CSF and blood serum of SCI patients with baseline American Spinal Injury Association Impairment Scale grades of A. The data obtained showed a large elevation of IL6 (>58 fold) in CSF and IFN-γ (>14 fold) in blood serum at 3 dpi with a downward trend as the post-traumatic period increases. The level of cytokine CCL26 was significantly elevated in both CSF and blood serum at 3 days post-SCI, while other cytokines did not show the same trend in the different biosamples. The dynamic changes in cytokine levels observed in our study can explore the relationships with the SCI region and injury severity, paving the way for a better understanding of the pathophysiology of SCI and potentially more targeted and personalized therapeutic interventions.

Knowledge Mapping of Macrophage in Spinal Cord Injury: A Bibliometric Analysis

Spinal cord injury (SCI) is a devastating condition, often leading to significant disability and impairment. As crucial immune cells, macrophages play a critical role in the pathophysiology of SCI. Understanding the current state of knowledge and research trends related to macrophages in SCI is crucial for developing effective therapeutic interventions. Using search strategies, we retrieved relevant articles from the Web of Science Core Collection (WOSCC), resulting in a robust dataset for analysis. VOSviewer, Citespace, and PRISM were employed for analysis and visualization. Various bibliometric indicators, including publication trends, citation analysis, co-authorship networks, and keyword analysis, were utilized to assess the scholarly landscape of macrophage research in SCI. Our findings revealed a steady increase in publications over the past 33years, indicating a growing interest in this field. We identified Popovich Phillip G was the most influential author, Ohio State University was the most influential institution, and identification of 2 distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord was the most influential paper in this field. This bibliometric analysis provides a comprehensive overview of the current knowledge landscape and research trends regarding macrophages in SCI. Neuroinflammation and macrophage polarization, transplation and molecular mechanism were emerging research areas and novel directions. Our study serves as a valuable resource for researchers in spinal cord injury research and therapeutic development.

Identification of RNA-binding Proteins in Spinal Cord Injury: An In-silico Approach

Introduction: Gene expression is regulated by trans-acting factors such as microRNA, and RNA-binding proteins (RBPs). Dysregulation of RNA-binding proteins (RBPs) are found in neurological diseases. However, the role RBPs in spinal cord injury (SCI) have not been identified. The objective of this study was to identify RBPs by re-analyzing RNA-sequencing data from SCI mice model using the latest version of Tuxedo pipeline. Methods: Reads from transcriptomic sequence of acute, subacute, and control mice models, from the Sequence Read Archive (SRA) website, were uploaded to a scientific workflow system called usegalaxy.org. The reads were assessed for their quality using FastQC, before they were mapped to the mouse mm10 reference genome using HISAT2. The fragments were then aligned to full-length transcripts using Stringtie, followed by DESeq2 to find differentially expressed genes (false discovery rate of 0.05 and fold change of -1&lt; x &gt;1). Finally, to find functional annotations, the Protein Analysis through Evolutionary Relationship (PANTHER) and g:Profiler were used. Results: There were 24 RBP-coding genes identified in the acute injury, and 27 in the subacute injury. Four RBPs that were commonly expressed at high levels in both acute and subacute injury; Hnrnpm, Ptbp3, Rbfox3 and Znf385a. These proteins regulate alternative splicing, and RNA transport. Other RBP-coding genes with a role in inflammatory response and apoptosis were also discovered. Conclusion: Novel RBP-coding genes differentially expressed in SCI were discovered, suggesting their role in the pathophysiology of SCI. These findings contribute to a better understanding of the regulatory mechanisms employed by RBPs in SCI.

Research progress on the application of transcranial magnetic stimulation in spinal cord injury rehabilitation: a narrative review.

Traumatic or non-traumatic spinal cord injury (SCI) can lead to severe disability and complications. The incidence of SCI is high, and the rehabilitation cycle is long, which increases the economic burden on patients and the health care system. However, there is no practical method of SCI treatment. Recently, transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, has been shown to induce changes in plasticity in specific areas of the brain by regulating the activity of neurons in the stimulation site and its functionally connected networks. TMS is a new potential method for the rehabilitation of SCI and its complications. In addition, TMS can detect the activity of neural circuits in the central nervous system and supplement the physiological evaluation of SCI severity. This review describes the pathophysiology of SCI as well as the basic principles and classification of TMS. We mainly focused on the latest research progress of TMS in the physiological evaluation of SCI as well as the treatment of motor dysfunction, neuropathic pain, spasticity, neurogenic bladder, respiratory dysfunction, and other complications. This review provides new ideas and future directions for SCI assessment and treatment.

The Influence of Exercise on Oxidative Stress after Spinal Cord Injury: A Narrative Review.

Spinal cord injury (SCI) is an irreversible disease resulting in partial or total loss of sensory and motor function. The pathophysiology of SCI is characterized by an initial primary injury phase followed by a secondary phase in which reactive oxygen species (ROSs) and associated oxidative stress play hallmark roles. Physical exercise is an indispensable means of promoting psychophysical well-being and improving quality of life. It positively influences the neuromuscular, cardiovascular, respiratory, and immune systems. Moreover, exercise may provide a mechanism to regulate the variation and equilibrium between pro-oxidants and antioxidants. After a brief overview of spinal cord anatomy and the different types of spinal cord injury, the purpose of this review is to investigate the evidence regarding the effect of exercise on oxidative stress among individuals with SCI.

Assessing the Feasibility of a Multimodal Approach to Pain Evaluation in Early Stages after Spinal Cord Injury.

This research evaluates the feasibility of a multimodal pain assessment protocol during rehabilitation following spinal cord injury (SCI). The protocol amalgamates clinical workup (CW), quantitative sensory testing (QST), and psychosocial factors (PSF) administered at 4 (T1), 12 (T2), and 24 (T3) weeks post injury and at discharge (T4). Molecular blood biomarkers (BB) were evaluated via gene expression and proteomic assays at T1 and T4. Different pain trajectories and temporal changes were identified using QST, with inflammation and pain-related biomarkers recorded. Higher concentrations of osteopontin and cystatin-C were found in SCI patients compared to healthy controls, indicating their potential as biomarkers. We observed altered inflammatory responses and a slight increase in ICAM-1 and CCL3 were noted, pointing towards changes in cellular adhesion linked with spinal injury and a possible connection with neuropathic pain. Despite a small patient sample hindering the correlation of feasibility data, descriptive statistical analyses were conducted on stress, depression, anxiety, quality of life, and pain interferences. The SCI Pain Instrument (SCIPI) was efficient in distinguishing between nociceptive and neuropathic pain, showing a progressive increase in severity over time. The findings emphasize the need for the careful consideration of recruitment setting and protocol adjustments to enhance the feasibility of multimodal pain evaluation studies post SCI. They also shed light on potential early adaptive mechanisms in SCI pathophysiology, warranting the further exploration of prognostic and preventive strategies for chronic pain in the SCI population.

Knockout of microglial Hv1 proton channel reduces neurotoxic A1 astrocytes and neuronal damage via the ROS/STAT3 pathway after spinal cord injury.

Spinal cord injury (SCI) causes severe functional deficits and neuronal damage, accompanied by intense glial activation. The voltage-gated proton channel Hv1, selectively expressed on microglia, is associated with SCI progression. However, the effect of Hv1 on the phenotypes and functions of reactive astrocytes after SCI remains unclear. Here, we combined Hv1 knockout (Hv1-/- ) mice and T10 spinal cord contusion to investigate the effects of microglial Hv1 on SCI pathophysiology and the phenotypes and functions of reactive astrocytes. After SCI, astrocytes proliferated and activated in the peri-injury area and exhibited an A1-dominant phenotype. Hv1 knockout reduced neurotoxic A1 astrocytes and shifted the dominant phenotype of reactive astrocytes from A1 to A2, enhancing synaptogenesis promotion, phagocytosis, and neurotrophy of astrocytes. Moreover, synaptic and axonal remodeling as well as motor recovery after SCI benefited from the improved astrocytic functions of Hv1 knockout. Furthermore, exogenous and endogenous reactive oxygen species (ROS) in astrocytes after SCI were reduced by Hv1 knockout. Our in vitro results showed that inhibition of ROS reduced the neurotoxic A1 phenotype in primary astrocytes via the STAT3 pathway. Similar to the effect of Hv1 knockout, the application of the ROS scavenger N-acetylcysteine reduced SCI-induced neurotoxic A1 astrocytes in vivo. Based on the in vivo and vitro results, we elucidated that microglial Hv1 knockout promotes synaptic and axonal remodeling in SCI mice by decreasing neurotoxic A1 astrocytes and increasing neuroprotective A2 astrocytes via the ROS/STAT3 pathway. Therefore, the Hv1 proton channel is a promising target for the treatment of SCI.

Co-Administration of Resolvin D1 and Peripheral Nerve-Derived Stem Cell Spheroids as a Therapeutic Strategy in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI), primarily caused by trauma, leads to permanent and lasting loss of motor, sensory, and autonomic functions. Current therapeutic strategies are focused on mitigating secondary injury, a crucial aspect of SCI pathophysiology. Among these strategies, stem cell therapy has shown considerable therapeutic potential. This study builds on our previous work, which demonstrated the functional recovery and neuronal regeneration capabilities of peripheral nerve-derived stem cell (PNSC) spheroids, which are akin to neural crest stem cells, in SCI models. However, the limited anti-inflammatory capacity of PNSC spheroids necessitates a combined therapeutic approach. As a result, we investigated the potential of co-administering resolvin D1 (RvD1), known for its anti-inflammatory and neuroprotective properties, with PNSC spheroids. In vitro analysis confirmed RvD1's anti-inflammatory activity and its inhibitory effect on pro-inflammatory cytokines. In vivo studies involving a rat SCI model demonstrated that combined therapy of RvD1 and PNSC spheroids outperformed monotherapies, exhibiting enhanced neuronal regeneration and anti-inflammatory effects as validated through behavior tests, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry. Thus, our findings suggest that the combined application of RvD1 and PNSC spheroids may represent a novel therapeutic approach for SCI management.

IL-6 in spinal cord injury: could immunomodulation replace immunosuppression in the management of acute traumatic spinal cord injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Selective Inhibition of Soluble Tumor Necrosis Factor Alters the Neuroinflammatory Response following Moderate Spinal Cord Injury in Mice.

Clinical and animal model studies have implicated inflammation and glial and peripheral immune cell responses in the pathophysiology of spinal cord injury (SCI). A key player in the inflammatory response after SCI is the pleiotropic cytokine tumor necrosis factor (TNF), which exists both in both a transmembrane (tmTNF) and a soluble (solTNF) form. In the present study, we extend our previous findings of a therapeutic effect of topically blocking solTNF signaling after SCI for three consecutive days on lesion size and functional outcome to study the effect on spatio-temporal changes in the inflammatory response after SCI in mice treated with the selective solTNF inhibitor XPro1595 and compared to saline-treated mice. We found that despite comparable TNF and TNF receptor levels between XPro1595- and saline-treated mice, XPro1595 transiently decreased pro-inflammatory interleukin (IL)-1β and IL-6 levels and increased pro-regenerative IL-10 levels in the acute phase after SCI. This was complemented by a decrease in the number of infiltrated leukocytes (macrophages and neutrophils) in the lesioned area of the spinal cord and an increase in the number of microglia in the peri-lesion area 14 days after SCI, followed by a decrease in microglial activation in the peri-lesion area 21 days after SCI. This translated into increased myelin preservation and improved functional outcomes in XPro1595-treated mice 35 days after SCI. Collectively, our data suggest that selective targeting of solTNF time-dependently modulates the neuroinflammatory response by favoring a pro-regenerative environment in the lesioned spinal cord, leading to improved functional outcomes.

Neuroprotective role of calreticulin after spinal cord injury in mice

Accumulating evidence suggests that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in the pathology of spinal cord injury (SCI). To determine the role of the UPR-target molecule in the pathophysiology of SCI, we analyzed the expression and the possible function of calreticulin (CRT), a molecular chaperone in the ER with high Ca2+ binding capacity, in a mouse SCI model. Spinal cord contusion was induced in T9 by using the Infinite Horizon impactor. Quantitative real-time polymerase chain reaction confirmed increase of Calr mRNA after SCI. Immunohistochemistry revealed that CRT expression was observed mainly in neurons in the control (sham operated) condition, while it was strongly observed in microglia/macrophages after SCI. Comparative analysis between wild-type (WT) and Calr+/- mice revealed that the recovery of hindlimb locomotion was reduced in Calr+/- mice, based on the evaluation using the Basso Mouse Scale and inclined-plane test. Immunohistochemistry also revealed more accumulation of immune cells in Calr+/- mice than in WT mice, at the epicenter 3 days and at the caudal region 7 days after SCI. Consistently, the number of damaged neuron was higher in Calr+/- mice at the caudal region 7 days after SCI. These results suggest a regulatory role of CRT in the neuroinflammation and neurodegeneration after SCI.

Current insights into the management of spinal cord injury

BackgroundTraumatic spinal cord injury (SCI) is a serious disorder that results in severe impairment of neurological function as well as disability, ultimately reducing a patient's quality of life. The pathophysiology of SCI involves a primary and secondary phase, which causes neurological injury. MethodsNarrative review on current clinical management of spinal cord injury and emerging therapies. ResultsThis review explores the management of SCI through early decompressive surgery, optimizing mean arterial pressure, steroid therapy and focused rehabilitation. These management strategies reduce secondary injury mechanisms to prevent the propagation of further neurological damage. The literature regarding emerging research is also explored in cell-based, gene, pharmacological and neuromodulation therapies, which aim to repair the spinal cord following the primary injury mechanism. ConclusionsOutcomes for patients with SCI can be enhanced and improved if primary and secondary phases of SCI can be addressed.