Search Results (267)

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

Background: Patients with ankylotic spines suffering from vertebral column fractures are frequently operated on to maintain spinal stability and prevent secondary displacement and nerve damage. The aim of this study was to identify a subset of patients that may be treated non-operatively, thus avoiding operative complications in this group of patients. Methods: Extension-type injuries in patients with DISH (diffuse idiopathic skeletal hyperostosis) not involving the posterior elements of the spine comprised the study group. Results: Twenty two extension fractures occurred in 21 patients with DISH in SZMC (Shaare Zedek Medical Cente) between 2014–2025. All patients were treated non-operatively. Patients were allowed free mobilization, and no orthosis was used. The only limitation was keeping the bed inclined to 20–30 degrees to prevent extension at the fracture site. All fractures healed uneventfully, and no patient required late surgical intervention, and no neurological complications were noted. Conclusions: Patients with DISH who sustain extension-type injuries of the thoracolumbar spine, with no involvement of the posterior elements, may be treated non-operatively, with good results. Full article

Spinal cord injury (SCI) is a major disability that, to this day, does not have a permanent cure. The spinal cord extends caudally through the body structure of the vertebral column and is part of the central nervous system (CNS). The spinal cord enables neural communication and motor coordination, so injuries can disrupt sensation, movement, and autonomic functions. Mechanical and traumatic damage to the spinal cord causes lesions to the nerves, resulting in the disruption of relayed messages to the extremities. Various forms of treatment for the spinal cord include functional electrical stimulation (FES), epidural electrical stimulation (EES), ‘SMART’ devices, exoskeleton and robotic systems, transcranial magnetic stimulation, and neuroprostheses using AI for the brain–computer interface. This research is going to analyse and review these current treatment methods for spinal cord injury and identify the current gaps and limitations in these, such as long-term biocompatibility, wireless adaptability, cost, regulatory barriers, and risk of surgery. Future advancements should work on implementing wireless data logging with AI algorithms to increase SCI device adaptability, as well as maintaining regulatory and health system integration. Full article

Oligodendrocyte precursor cells (OPCs) are a distinct and dynamic glial population that retain proliferative and migratory capacities throughout life. While traditionally recognized for differentiating into oligodendrocytes (OLs) and generating myelin to support rapid nerve conduction, OPCs are now increasingly appreciated for their diverse and non-canonical roles in the central nervous system (CNS), including direct interactions with neurons. A notable feature of OPCs is their expression of diverse ion channels that orchestrate essential cellular functions, including proliferation, migration, and differentiation. Given their widespread distribution across the CNS, OPCs are increasingly recognized as active contributors to the development and progression of various neurological disorders. This review aims to present a detailed summary of the physiological and pathological functions of ion channels in OPCs, emphasizing their contribution to CNS dysfunction. We further highlight recent advances suggesting that ion channels in OPCs may serve as promising therapeutic targets across a broad range of disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury, amyotrophic lateral sclerosis (ALS), psychiatric disorders, Alzheimer’s disease (AD), and neuropathic pain (NP). Finally, we discuss emerging therapeutic strategies targeting OPC ion channel function, offering insights into potential future directions in the treatment of CNS diseases. Full article

Neuropathic pain resulting from injury to the somatosensory nervous system affects approximately 6.9–10% of the general population and significantly impacts quality of life. Common presentations include burning, stabbing, tingling, or electrical sensations, occurring spontaneously or through hyperalgesia or allodynia. Treatment approaches follow a tiered system. First-line therapies include gabapentinoids (e.g., gabapentin, pregabalin), which target voltage-gated calcium channels; tricyclic antidepressants (e.g., amitriptyline, nortriptyline); and serotonin-norepinephrine reuptake inhibitors such as duloxetine. Second-line options encompass topical agents (e.g., 5% lidocaine, 8% capsaicin), opioid-like medications (e.g., tramadol, tapentadol), and adjunctive therapies including psychological therapies and lifestyle interventions. For refractory cases, third-line treatments include NMDA receptor antagonists (e.g., ketamine, dextromethorphan), cannabinoids, and botulinum toxin type A, though these have more limited clinical evidence. Procedural interventions such as spinal cord stimulation and transcutaneous electrical nerve stimulation provide alternatives when pharmacological approaches fail. Despite advances in treatment options, many patients remain undertreated, highlighting the need for individualized, multimodal approaches and continued research into the complex pathophysiology of neuropathic pain conditions. Full article

Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1′,1′-dimethylheptyl-Δ⁸-tetrahydrocannabinol-11-oic acid (CT-3), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), combinations of Δ⁹-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes. Full article

Neuropathic pain results from a lesion or disease affecting the somatosensory nervous system. Injury to primary afferent nerves leads to microgliosis in the spinal dorsal horn (SDH), which plays a crucial role in developing neuropathic pain. Within the SDH, primary afferent fibers broadly project, and microglia are nearly ubiquitously distributed under normal conditions. However, not all microglia react to injuries affecting primary afferent fibers, resulting in spatially heterogeneous microgliosis within the SDH. The mechanisms underlying this phenomenon remain elusive. In this study, the spatial relationship between microgliosis and the projections of injured nerves was investigated by generating mice that had expressed tdTomato in the fourth lumbar dorsal root ganglion (L4-DRG) neurons via intra-L4-spinal nerve (SpN) injection of adeno-associated viral vectors. After transection of the L4-SpN, we found that microgliosis in the SDH selectively occurred in the innervation territories of the injured primary afferent fibers. However, denervating transient receptor potential vanilloid 1 (TRPV1)-expressing primary afferent fibers in the SDH through intrathecal injection of capsaicin did not trigger microgliosis, nor did it influence the microgliosis induced by L4-SpN injury. Conversely, pharmacological damage to myelinated DRG neurons, including Aβ-fibers, was sufficient to induce microgliosis. Furthermore, L4-SpN injury also induced microgliosis in the gracile nucleus, which primarily receives innervation from Aβ-fibers. These findings suggest that microgliosis in the SDH shortly after peripheral nerve injury is predominantly associated with damage to primary afferent Aβ-fibers. Full article

Spinal motor nerve root lesions can happen after avulsion or crush, generating acute motoneuron death and synaptic loss, consequently, causing motor and sensory dysfunctions. Local response is mediated by astroglial and microglial cells, giving rise to a pro-inflammatory profile. TEMPOL and DMF are drugs that have been studied in our laboratory after spinal cord nerve root injuries and have demonstrated significant results in terms of neuroprotection and immunomodulation, decreasing the inflammation process. In the present work, a flow cytometry approach was used to evaluate cellular responses to injury and immunomodulation. For this, injured animals received TEMPOL, DMF or vehicle once a day for 7, 14 or 28 days of treatment. Flow cytometry multiparametric analysis allowed the quantification of different pro- and anti-inflammatory glial, macrophage and lymphocyte markers. Contrasting with the vehicle treated counterpart, TEMPOL and DMF led to downregulation of pro-inflammatory cytokines in astrocytes and microglia subpopulations, but did not show significant results in increasing anti-inflammatory phenotypes. As for macrophage and lymphocyte subpopulations, both treatments showed a balance between pro- and anti-inflammatory phenotypes. Therefore, it was concluded that both drugs exhibit immunomodulatory action, contributing to a pro-regenerative profile in the tissue. Full article

The strong correlation between evoked potentials (EPs) and American Spinal Injury Association (ASIA) scores in individuals with spinal cord injury (SCI) suggests that EPs may serve as reliable predictive markers for rehabilitation progress. Numerous studies have confirmed a relationship between variations in somatosensory evoked potentials (SSEPs) and ASIA scores, especially in the early stages of SCI. Machine learning’s (ML’s) increasing importance in medicine is driven by the growing availability of health data and improved algorithms. It enables the creation of predictive models for disease diagnosis, progression prediction, personalized treatment, and improved healthcare efficiency. Data-driven approaches can significantly improve patient care, reduce costs, and facilitate personalized medicine. The meticulous analysis of medical data is crucial for timely disease identification, leading to effective symptom management and appropriate treatment. This study applies artificial intelligence to identify predictors of SCI progression, as measured by the disability index, ASIA impairment scale (AIS), and final motor recovery. We aim to clarify the prognostic role of electrophysiological testing (SSEPs, MEPs, and nerve conduction studies (NCSs)) in SCI. We analyzed data from a medical database of 123 records. We developed an ML-based intelligent system, utilizing ensemble algorithms combining decision trees and neural network approaches, to predict SCI recovery. Our evaluation showed SEP accuracies of 90% for motor recovery prediction and 80% for AIS scale determination, comparable to full electrophysiology evaluation accuracies of 93% and 89%, respectively, and generally superior results compared to MEP and NCS results. EPs emerged as the best predictors, comparable to a comprehensive electrophysiology assessment, significantly improving accuracy compared to clinical findings alone. An electrophysiological assessment, when available, increased overall accuracy for final motor recovery prediction to 93% (from a maximum of 75%) and, for ASIA score determination, to 89% (from a maximum of 66%). Further validation is needed with a larger dataset. Future research should validate that sensory electrophysiology assessment is a less expensive, portable, and simpler alternative to other prognostic tests and more effective than clinical assessments, like the AIS, biomarker for SCI, and personalized rehabilitation planning. Full article

Molecules involved in the activation of regeneration in reptiles are almost unknown. MARCK-like proteins are indicated to activate regeneration in some amphibians and fish, and it would be important to know whether this is a general process also present in other vertebrates. To address this problem, the present study reports the immunolocalization of a MARCK-like protein in injured tissues of a lizard. Bioinformatics and immunofluorescence after 5BrdU administration, and detection of MARCK-like proteins, have been performed on regenerating tail and limb of the lizard Podarcis muralis. Transcriptome data indicate up-regulation of MARCKS and MARCK-like1 expression in the initial regenerating tail and limb blastemas, supporting their involvement in the activation of regeneration in both appendages. Immunofluorescence for 5BrdU shows numerous proliferating cells in the blastemas of both appendages. Immunolocalization of a MARCK-like protein, using an antibody generated against a homologous protein from the axolotl, shows that the wound epidermis, nerves, and myotubes accumulate most of the protein in the limb and tail. MARCK-like immunolabeling is also detected in the regenerating spinal cord of the tail. The study indicates that, although the limb later turns into a scar, the MARCK-like protein is also up-regulated in this appendage, like in the regenerating tail. These results indicate that the initial reaction to an injury in lizards, an amniote representative, includes some triggering processes observed in amphibians and fish (anamniotes), with the activation of MARCK-like genes and proteins. This suggests that a MARCK-like-dependant mechanism for tissue repair is likely activated during the initial phases of vertebrate wound healing. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse event with unclear mechanisms and limited treatment alternatives. This study aimed to investigate the efficacy of two alkalizing agents, a mixture of potassium citrate and sodium citrate (K/Na citrate) or sodium bicarbonate (NaHCO₃), in preventing and treating paclitaxel (PTX)-induced mechanical allodynia in rodents. The results from rodent models demonstrated that repeated prophylactic administration of K/Na citrate or NaHCO₃ could inhibit the development of PTX-induced mechanical allodynia. Moreover, K/Na citrate was effective in preventing the PTX-induced exacerbation of mechanical allodynia, even when treatment was initiated immediately after the onset of allodynia. K/Na citrate also reduced the levels of the plasma complement component anaphylatoxin C3a in a PTX-induced CIPN rat model. Complement activation, resulting in the production of C3a, has been implicated in the pathogenesis of this model. Additionally, pretreatment with Na citrate significantly prevented the reduction in neurite outgrowth caused by PTX. Furthermore, K/Na citrate inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons. These findings indicate that K/Na citrate may regulate the development of PTX-induced mechanical allodynia by modulating complement activation and providing neuroprotection against PTX-induced peripheral nerve injury. This study implies that alkalization could help prevent PTX-induced peripheral neuropathy and mitigate its exacerbation. Full article

Recent studies have revealed marked sex differences in pathophysiological roles of spinal microglia in neuropathic pain, with microglia contributing to pain exacerbation exclusively in males. However, the characteristics of pain-enhancing microglia, which are more prominent in males, remain poorly understood. Here, we reanalyzed a previously published single-cell RNA sequencing dataset and identified a microglial subpopulation that significantly increases in the spinal dorsal horn (SDH) of male mice following peripheral nerve injury. CC-chemokine ligand 4 (CCL4) was highly expressed in this subpopulation and its mRNA levels were increased in the SDH after partial sciatic nerve ligation (PSL) only in male mice. Notably, CCL4 expression was reduced in male mice following microglial depletion, indicating that microglia are the primary source of CCL4. Intrathecal administration of maraviroc, an inhibitor of the CCL4–CC-chemokine receptor 5 (CCR5) signaling pathway, after PSL, significantly suppressed mechanical allodynia only in male mice. Furthermore, intrathecal administration of CCL4 induced mechanical allodynia in both sexes, accompanied by increased expression of c-fos, a neuronal excitation marker, in the SDH. These findings highlight a sex-biased difference in the gene expression profile of spinal microglia following peripheral nerve injury, with elevated CCL4 expression in male mice potentially contributing to pain exacerbation. Full article

Spinal cord injury (SCI) affects millions of people worldwide. One of the main challenges of rehabilitation strategies is re-training and enhancing the plasticity of the spinal circuitry that was preserved or rebuilt after the injury. The serotonergic system appears to be crucial in these processes, since recent studies have reported the capability of serotonergic (5-HT) axons for axonal sprouting and regeneration in response to central nervous system (CNS) trauma or neurodegeneration. We took advantage of tryptophan hydroxylase 2 knockout (TPH2 KO) rats, lacking serotonin specifically in the brain and spinal cord, to study the role of the serotonergic system in the recovery of sensorimotor function after SCI. In the present work, we compared the rate of sensorimotor recovery of TPH2 KO and wild-type (WT) female rats after SCI (lateral hemisection at the T8 spinal level). SCI caused severe motor impairments in the ipsilateral left hindlimb, the most pronounced in the first week after the hemisection with gradual functional recovery during the following 3 weeks. The results demonstrate that TPH2 KO rats have less potential to recover motor functions since the degree of sensorimotor deficit in the tapered beam walking test (TBW) and ladder walking test (LW) was significantly higher in the TPH2 KO group in comparison to the WT animals in the 3rd and 4th weeks after SCI. The recovery dynamics of the hindlimb muscle tone and voluntary movements was in agreement with the restoration of motor performance in TBW and LW. Compound muscle action potential analysis in the gastrocnemius (GM) and tibialis (TA) muscles of both hindlimbs after electrical stimulation of the sciatic nerve or lumbar region (L5–L6) of the spinal cord indicated slower recovery of sensorimotor pathways in the TPH2 KO group versus their WT counterparts. In general, the observed results confirm the significance of central serotonergic mechanisms in the recovery of sensorimotor functions in rats and the relevance of the TPH2 KO rat model in studying the role of the 5-HT system in neurorehabilitation. Full article

Background: The dorsal scapular nerve (DSN) and the long thoracic nerve (LTN) exhibit variable anatomical pathways, which may contribute to upper back pain and impaired scapular movement in affected patients. This study investigates these variations to enhance clinicians’ diagnostic and surgical approaches. Methods: The bilateral cervical regions of 32 formalin-embalmed donors (64 sides) were dissected to document the origin of the DSN, the relationship with the scalene muscles of the DSN, and anatomical connections between the DSN and LTN. Measurements of the distance between the mastoid process and the piercing point of the DSN to the scalene muscle were obtained with digital calipers. Additional measurements were obtained from the medial border of the scapula at two specific locations: the scapular spine (zone 1) and the midpoint between the scapular spine and the inferior angle of the scapula (zone 2). Results: The DSN demonstrated four distinct cervical spinal nerve root origins and five unique scalene muscle piercing patterns. The average distance between the DSNs’ scalene muscle piercing point and the mastoid process was 94.87 ± 10.09 mm, with significantly greater distances observed in male donors compared to female donors (p < 0.001). Connections between the DSN and LTN were identified in 65.2% of the examined cervical regions. The mean distance of the DSN from the medial border of the scapula at zone 2 was significantly greater than at zone 1 (p < 0.001). Conclusions: The anatomical variation findings and classification of the DSN provide valuable insights, offering guidance for conducting clinical procedures of the scalene and rhomboid musculature in a way that minimizes the risk of iatrogenic injury. The documented variations may also assist in the diagnosis and management of DSN-related pathologies such as DSN neuropathy. Full article

Neuropathic pain (NP) is a type of chronic pain resulting from injury or dysfunction of the nerves or spinal cord. Previous studies have shown that the combination of ligustrazine (LGZ) and sinomenine (SIN) exerts a synergistic antinociceptive effect in peripheral and central NP models. On this basis, a comprehensive analgesic evaluation was performed in a chronic constriction injury (CCI)-induced NP model in rats. Sciatic nerve histopathological changes were observed, and 22 cytokines and chemokines levels were analyzed. We also combined network pharmacology and metabolomics to explore their molecular mechanisms. Results showed that the combination of LGZ and SIN significantly alleviated the pain-like behaviors in CCI rats in a time- and dose-dependent manner, demonstrating superior therapeutic effects compared to LGZ or SIN alone. It also improved pathological damage to sciatic nerves and regulated inflammatory cytokine levels. Network pharmacology identified shared and distinct pain-related targets for LGZ and SIN, while metabolomics revealed 54 differential metabolites in plasma, and 17 differential metabolites in CSF were associated with the combined intervention of LGZ and SIN. Finally, through an integrated analysis of the core targets and differential metabolites, tyrosine metabolism, phenylalanine metabolism, and arginine and proline metabolism were identified as potential key metabolic pathways underlying the therapeutic effects of LGZ and SIN in CCI treatment. In conclusion, our study provides evidence to support the clinical application of LGZ and SIN in the treatment of NP. Full article