Search Results (748)

Background/Objectives: The spinal cord is a critical component of the central nervous system that transmits neural signals between the brain and the body’s peripheral regions through its nerve roots. Despite being partially protected by the vertebral column, the spinal cord remains highly vulnerable to trauma, tumors, infections, and degenerative or inflammatory disorders. These conditions can disrupt neural conduction, resulting in severe functional impairments, such as paralysis, motor deficits, and sensory loss. Therefore, accurate and comprehensive spinal cord segmentation is essential for characterizing its structural features and evaluating neural integrity. Methods: In this study, we propose a fully automated method for segmentation of the cervical spinal cord in sagittal magnetic resonance (MR) images. This method facilitates rapid clinical evaluation and supports early diagnosis. Our approach uses a Swin-Unet architecture, which integrates vision transformer blocks into the U-Net framework. This enables the model to capture both local anatomical details and global contextual information. This design improves the delineation of the thin, curved, low-contrast cervical cord, resulting in more precise and robust segmentation. Results: In experimental studies, the proposed Swin-Unet model (SWU1), which uses transformer blocks in the encoder layer, achieved Dice Similarity Coefficient (DSC) and Hausdorff Distance 95 (HD95) scores of 0.9526 and 1.0707 mm, respectively, for cervical spinal cord segmentation. These results confirm that the model can consistently deliver precise, pixel-level delineations that are structurally accurate, which supports its reliability for clinical assessment. Conclusions: The attention-enhanced Swin-Unet architecture demonstrated high accuracy in segmenting thin and complex anatomical structures, such as the cervical spinal cord. Its ability to generalize with limited data highlights its potential for integration into clinical workflows to support diagnosis, monitoring, and treatment planning. Full article

Background/Objectives: Biochemical processes such as the glycolytic pathway and Kreb’s cycle are important in producing ATP for the brain. Without a sufficient supply of glucose for energy metabolism, the brain cannot efficiently regulate or coordinate the actions and reactions of the body. It is well documented that traumatic brain injury (TBI) is associated with reduced energy metabolism through the production of reactive oxygen/nitrogen species. Antioxidants, such as glutathione (GSH), have been shown to combat the deleterious effects of oxidation by scavenging ROS/RNS, inhibiting propagation, and removing neurotoxic byproducts. Gamma-glutamylcysteine ethyl ester (GCEE), an ethyl ester moiety of gamma-glutamylcysteine, exhibits antioxidant activity by increasing GSH production. This therapeutic has protective effects against oxidative stress through the elevation of glutathione. Methods: This study investigates the enzymatic activities of several key energy-related proteins that have been identified as nitrated in treated Wistar rats with moderate TBI. To test the hypothesis that the elevation of GSH production upon administration of GCEE will normalize enzymatic activity post-TBI, adult male Wistar rats were equally divided into three groups: sham, saline, and GCEE. Rats were treated with 150 mg/kg saline or GCEE at 30 and 60 min post-TBI. Upon sacrifice, brains were harvested and enzymatic activity was measured spectrophotometrically. Results: An increase in enzymatic activity upon GSH elevation via GCEE administration in several key enzymes was observed. Conclusions: GCEE is a potential therapeutic strategy to restore energy-related proteins in the brain post-TBI via GSH elevation. Full article

Calcium-dependent cysteine proteases, known as calpains, emerge as important regulators of spinal cord physiology, plasticity, and pathology. First characterized in the brain, they influence a wide range of processes in the spinal cord, maintaining neuronal homeostasis, shaping both synaptic and intrinsic plasticity, and modulating glial responses. When dysregulated, calpains contribute to the pathophysiology of traumatic and neurodegenerative spinal cord disorders, as well as to their associated motor and sensory complications, including spasticity and neuropathic pain. A recurring feature of these conditions is calpain-mediated proteolysis of ion channels, transporters, and cytoskeletal proteins, which promotes disinhibition and neuronal hyperexcitability. The resultant protein fragments are examined as prospective biomarkers for damage and disease progression. Meanwhile, promising strategies for neuroprotection and functional recovery in the clinic emerge as a result of innovative pharmacological and genetic approaches to modulate calpain activity. In this review, we present the current state of knowledge regarding the functions and regulation of calpains in the spinal cord and assess their translational potential as both therapeutic targets and effectors in spinal cord disorders. Full article

Background: Animal-assisted activities (AAA) are participative interventions, designed to lower hospitalization-related stress and anxiety, enhance communicative readiness, improve quality of life and encourage human–animal interaction. The aim of the present study was to evaluate AAA effects in the context of intensive rehabilitation of patients with spinal cord injury (SCI), traumatic brain injury (TBI), stroke. Methods: AAA in this study were structured by a local specialized association, for small groups of patients (5/7 a time), biweekly; each session lasted 60 min. Each patient participated in 10 sessions of AAA. Evaluation rating scales were administered at T0 (before the first session) and T1 (after the last session, five weeks later) as follows: Neurobehavioral Rating Scale (NRS) in case of patient with stroke/TBI without disorder of consciousness; Hospital Anxiety and Depression Scale (HADS) for SCI patients. Results: A total of 50 patients concluded the study. NRS score for joined TBI and stroke populations varied from a T0 mean value of 32.34 [C.I. 26.83–37.35] to 17.21 [C.I. 12.66–21.76] (46.7%); this difference proved to be statistically significant (p = 0.000). Stroke patients had a 57.6% NRS lowering by mean 28.10 [C.I. 20.55–35.65] points to 12 [C.I. 6.6–17.36], which was significant (p = 0.000); similarly, TBI patients showed a mean decrease of 35.8% points from the initial 41.6 points [C.I. 37.29–45.93] to 26.76 [C.I. 21.94–31.59] (p = 0.002). As for HADS scores a smaller improvement was found in the cohort of SCI patients: anxiety registered a 1 mean point decrease at T1 (21.5%), from the initial 6.5 points [C.I. 3.80–9.34] to 5.1 ones [C.I. 3.17–7.11]. This variation was near the threshold of significance (p = 0.05). Depression domain, instead, improved by 2.35 mean points (37%), from the 6.35 initial points [C.I. 3.45–9.26] to the final 4 [C.I. 2.15–5.98] with reaching of a significant p value (p = 0.03). ANCOVA did not confirm this last value and showed no influence of age and gender on outcome variations. Discussion: AAA showed preliminary evidence to decrease neurobehavioral disorders in patients with high-complexity neurological diseases, particularly stroke and TBI. The role of AAA in SCI patients remains unclear. Future studies should address confounders’ role for these populations, particularly severity of disease. Furthermore, AAA interventions will have to be studied on larger samples, deepening the exact phase to introduce AAA for neurological patients. Lastly, qualitative studies are needed to explore patients’ lived experiences. Full article

Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide a unifying framework for diagnosis and management. A structured search of PubMed, Scopus, and Web of Science identified English-language clinical and mechanistic studies addressing CTC-mediated pain, with case reports excluded unless mechanistically informative. We propose multidimensional refractoriness criteria that integrate pharmacological non-response, failed interventional strategies, and objective functional impairment. Current treatments span pharmacotherapy, peripheral interventions (nerve blocks, radiofrequency ablation), and neuromodulation at multiple network levels (occipital nerve stimulation, spinal cord stimulation, motor cortex stimulation, deep brain stimulation). Non-invasive approaches such as rTMS, tDCS, and vagus nerve stimulation are emerging but remain investigational. Advances in imaging and neurophysiological biomarkers now permit greater precision in detecting CTC dysfunction and tailoring therapy. By combining anatomical precision, mechanistic insight, and multidisciplinary strategies, this review proposes a clinically actionable definition of refractoriness and supports a stepwise, mechanism-based approach to therapy. CTC emerges as a targetable hub for diagnostic and therapeutic strategies in refractory head and neck pain. Full article

Neurodegenerative diseases (NDDs) represent a class of incurable and progressive disorders characterized by the gradual degeneration of the structure and function of the nervous system, particularly the brain and spinal cord. A range of innovative therapeutic approaches is currently under investigation, such as stem cell-based therapies, gene-editing platforms such as CRISPR, and immunotherapies directed at pathogenic proteins. Moreover, phytochemicals such as β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models. These natural agents exert multifaceted effects by modulating neuroinflammatory pathways, oxidative stress responses, and aberrant protein aggregation—pathological mechanisms that are central to the development and progression of neurodegenerative disorders. Recent investigations have increasingly emphasized the optimization of the pharmacokinetic properties of β-caryophyllene and xanthohumol through the development of advanced drug-delivery systems, including polymer- and lipid-based nano- and microscale carriers. Such advancements not only enhance the bioavailability and therapeutic potential of these phytochemicals but also underscore their growing relevance as natural candidates in the development of future interventions for neurodegenerative disorders. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal type of neurodegenerative disease marked by progressive and selective degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. However, the intricate molecular mechanisms underlying primary cell death pathways, including ferroptosis-related genes (FRGs) mediating MN dysfunction in ALS, remain elusive. Ferroptosis, a novel type of iron-dependent cell death with the accumulation of lipid peroxidation products, stands distinct from apoptotic-related stress and other cell death mechanisms. Although growing advances have highlighted the role of iron deposition, apoptosis and alteration of antioxidant systems in ALS pathogenesis, there is little data at the systems biology level. Therefore, we performed a comprehensive bioinformatic analysis of bulk RNA-sequencing (RNA-seq) data by systematically comparing the gene expression profiles from iPSC-derived MNs of ALS patients and healthy controls using our datasets as well as from the GEO database to reveal the role of ferroptosis-related gene alterations in ALS, especially in selective MN vulnerability of FUSED IN SARCOMA (FUS) mutations. In this study, we first identified differentially expressed genes (DEGs) between FUS mutant and healthy controls. Subsequently, the crossover genes between DEGs and FRGs were selected as differentially expressed ferroptosis-related genes (DEFRGs). Functional enrichment and protein–protein interaction (PPI) analysis of DEFRGs identified that DNA damage, stress response and extra cellular matrix (ECM) were the most significantly dysregulated functions/pathways in FUS-ALS causing mutations compared to healthy controls. While GSEA analysis showed enrichment of genes associated with apoptosis, the degree of ferroptosis and iron ion homeostasis/response to iron of FUS MNs was lower. Altogether, our findings may contribute to a better understanding of the relevant role of cell death pathways underlying selective vulnerability of MNs to neurodegeneration in FUS-ALS pathophysiology. Full article

The African turquoise killifish is a short-lived vertebrate that is gaining interest as a model for understanding degenerative processes associated with aging, including neurodegeneration. However, due to its relatively recent adoption in laboratory research, detailed studies on the adult neuroanatomy of the killifish, particularly regarding the organization of neurotransmitter systems and their age-related changes, remain limited. Here, we study the organization of serotonergic cell populations in the brain and spinal cord of juvenile/young adult (1–3-months-old) and geriatric (5–6-months-old) killifish using anti-serotonin immunofluorescence. Our findings reveal that the overall organization of serotonergic cell populations in killifish closely resembles that of most teleosts, including pineal, pretectal, hypothalamic, rapheal and spinal cord neuronal populations. Of note, adult killifish also present a population of serotonergic neurons in the dorsolateral isthmus, which has been only described in a few other fish species. Aged killifish showed a similar organization of serotonergic cell populations to that of juveniles/young adults, with the major difference being the loss of serotonin immunoreactivity in pretectal cells of 6-month-old fish. Our study provides a neuroanatomical framework for future investigations into the serotonergic system in this emerging vertebrate model of aging. Full article

Medical physicists are transforming physiological measurements and electrophysiological applications by addressing challenges like motion artifacts and regulatory compliance through advanced signal processing, artificial intelligence (AI), and statistical rigor. Their innovations in wearable electrophysiology achieve 8–12 dB signal-to-noise ratio (SNR) improvements in EEG, 60% motion artifact reduction, and 94.2% accurate AI-driven arrhythmia detection at 12 μW power. In precision neurology, machine learning (ML) with evoked potentials (EPs) predicts spinal cord injury (SCI) recovery and multiple sclerosis (MS) progression with 79.2% accuracy based on retrospective data from 560 SCI/MS patients. By integrating multimodal data (EPs, MRI), developing quantum sensors, and employing federated learning, these can enhance diagnostic precision and prognostic accuracy. Clinical applications span epilepsy, stroke, cardiac monitoring, and chronic pain management, reducing diagnostic errors by 28% and optimizing treatments like deep brain stimulation (DBS). In this paper, we review the current state of wearable devices and provide some insight into possible future directions. Embedding medical physicists into standardization efforts is critical to overcoming barriers like quantum sensor power consumption, advancing personalized, evidence-based healthcare. Full article

Traumatic injuries to the brain and spinal cord remain among the most challenging conditions in clinical neuroscience due to the complexity of repair mechanisms and the limited regenerative capacity of neural tissues. Nanotechnology has emerged as a transformative field, offering precise diagnostic tools, targeted therapeutic delivery systems, and advanced scaffolding platforms that are capable of overcoming the biological barriers to regeneration. This review summarizes the recent advances in nanoscale diagnostic markers, functionalized nanoparticles for drug delivery, and nanostructured scaffolds designed to modulate the injured microenvironment and support axonal regrowth and remyelination. Emerging evidence indicates that nanotechnology enables real-time, minimally invasive detection of inflammation, oxidative stress, and cellular damage, while improving therapeutic efficacy and reducing systemic side effects through targeted delivery. Electroconductive scaffolds and hybrid strategies that integrate electrical stimulation, gene therapy, and artificial intelligence further expand opportunities for personalized neuroregeneration. Despite these advances, significant challenges remain, including long-term safety, immune compatibility, the scalability of large-scale production, and translational barriers, such as small sample sizes, heterogeneous preclinical models, and limited follow-up in existing studies. Addressing these issues will be critical to realize the full potential of nanotechnology in traumatic brain and spinal cord injury and to accelerate the transition from promising preclinical findings to effective clinical therapies. Full article

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is characterized by the predominance of optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), and cortical encephalitis, and can be diagnosed by the presence of pathogenic immunoglobulin G (IgG) antibodies targeting the extracellular domain of MOG in the serum and cerebrospinal fluid (CSF). Initially considered a variant of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), it is now widely recognized as a separate entity, supported by converging evidence from serological, pathological, and clinical studies. Patients with MOGAD often exhibit better recovery from acute attacks; however, their clinical and pathological features vary based on the immunological role of MOG-IgG via antibody- or complement-mediated perivenous demyelinating pathology, in addition to MOG-specific cellular immunity, resulting in heterogeneous demyelinated lesions from vanishing benign forms to tissue necrosis, even though MOGAD is not a mild disease. The key is the immunological mechanism of devastating lesion coalescence and long-term degenerating mechanisms, which may still accrue, particularly in the relapsing, progressing, and aggressive clinical course of encephalomyelitis. The warning features of the severe clinical forms are: (1) fulminant acute multifocal lesions or multiphasic ADEM transitioning to diffuse (Schilder-type) or tumefactive lesions; (2) cortical or subcortical lesions related to brain atrophy and/or refractory epilepsy (Rasmussen-type); (3) longitudinally extended spinal cord lesions severely affected with residual symptoms. In addition, it is cautious for patients refractory to acute stage early 1st treatment including intravenous methylprednisolone treatment and apheresis with residual symptoms and relapse activity with immunoglobulin and other 2nd line treatments including B cell depletion therapy. Persistent MOG-IgG high titration, intrathecal production of MOG-IgG, and suggestive markers of higher disease activity, such as cerebrospinal fluid interleukin-6 and complement C5b-9, could be identified as promising markers of higher disease activity, worsening of disability, and poor prognosis, and used to identify signs of escalating treatment strategies. It is promising of currently ongoing investigational antibodies against anti-interleukin-6 receptor and the neonatal Fc receptor. Moreover, due to possible refractory issues such as the intrathecal production of autoantibody and the involvement of complement in the worsening of the lesion, further developments of other mechanisms of action such as chimeric antigen receptor T-cell (CAR-T) and anti-complement therapies are warranted in the future. Full article

Meningococcal meningitis is a deadly acute bacterial infection caused by the Neisseria meningitidis bacterium that affects the membrane covering the brain and spinal cord. The World Health Organization launched the “Defeating bacterial meningitis by 2030” initiative in 2018, which relies on recent discoveries of cheap and effective vaccines. Here, we consider one important factor—human behavior—which is often neglected by immunization campaigns. We constructed a game-theoretic model of meningitis in the meningitis belt, where individuals make selfish rational decisions whether to vaccinate based on the assumed costs and the vaccination decisions of the entire population. We identified conditions when individuals should vaccinate, and we found the optimal (equilibrium) population vaccination rate. We conclude that voluntary compliance significantly reduces the endemic levels of meningitis if the cost of vaccination relative to the cost of the disease is sufficiently low, but it does not eliminate the disease. We also performed uncertainty and sensitivity analysis on our model. Full article

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

Background: multiple sclerosis (MS) presentation varies depending on the location and severity of the lesions affecting different areas of the spinal cord and brain. Extensive research has focused on specific systems to detect the disease in its various stages. The objective of this study was to investigate the concentration of the soluble scavenger receptor for haptoglobin–haemoglobin complex (Hb-Hp), sCD163, which is mostly expressed by monocytes and protects tissues from oxidative damage, in patients with MS. Methods: enzyme-Linked Immunosorbent Assay (ELISA) analysis was conducted in plasma samples collected from twenty-three relapsing–remitting MS (RRMS) subjects treated with teriflunomide and ten healthy control subjects (HCs). Results: the study results showed no differences between RRMS subjects and HCs in the concentration of CD163. A significantly higher concentration of sCD163 in RRMS was found in men in comparison to women (p = 0.038, Cohen d = 0.97). Conclusions: a significant correlation between disease activity, estimated using plasma-soluble CD163 (sCD163) and clinical assessment of the Expanded Disability Status Scale (EDSS) (p = 0.021), was detected in female patients with RRMS. Full article

Regulatory T cells (Tregs) have anti-inflammatory immunomodulatory activity and hold therapeutic potential for chronic neuroinflammatory neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). We are developing engineered human Tregs with enhanced disease-modifying activity for treating ALS. A combination of a disease-specific chimeric antigen receptor (CAR) recognizing misfolded human superoxide dismutase-1 (hSOD1) and constitutive expression of brain-derived neurotrophic factor (BDNF) was tested. The scFv region of CAR demonstrated binding to anterior horn tissues of ALS patients with and without familial ALS mutations in SOD1. Tregs transduced to express BDNF showed the ability to secrete BDNF and protect co-cultured neuronal cells from peroxidase toxicity. Co-expression of BDNF did not inhibit CAR Treg expansion, Treg markers, or CAR-mediated anti-inflammatory cytokine production. Human Tregs co-expressing CAR and BDNF were tested for activity in G93A hSOD1-NSG transgenic mice, which develop an early-onset and aggressive ALS-like disease and do not reject human cells. Human Tregs expressing CAR and BDNF delayed the onset of disease development, extended survival, and decreased spinal cord neuroinflammation. The engineered Tregs showed enhanced disease-modifying activity and hold promise as a therapy for ALS. Full article