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BACKGROUND: Depression is a prevalent and serious mental health disorder that significantly impacts daily life and functioning. Neurofilament Light chain (NfL), associated with axonal neuronal damage, has been identified as a promising biomarker, potentially aiding in early diagnosis of depression, personalized treatment, and tracking disease progression. This study used meta-analysis to evaluate the potential of plasma NfL as a biomarker for depression patients. METHODS: A systematic search following the PRISMA guidelines was conducted across PubMed, Web of Science, Scopus, and Google Scholar databases to find relevant studies on plasma NfL levels in patients with depression. A random effects model meta-analysis was applied to determine its potential as a biomarker for differentiating patients from controls. RESULTS: Our meta-analysis, based on four articles with six datasets, revealed that plasma NfL levels were notably higher in individuals with depression (228 cases) compared to healthy controls (118 individuals). The weighted mean difference (WMD) was 8.78 (95% CI: 5.28, 12.28; P < 0.01), indicating a significant effect size. Given the diverse confounding factors inherent in the included observational studies, the observed variability can be attributed to these influences. Due to the observed heterogeneity (heterogeneity Chi-Square: 54.91, p < 0.05), we performed a subgroup analysis. Subgroup analyses based on depression type and analysis method consistently supported the association between NfL and depression, strengthening the evidence. CONCLUSION: Our meta-analysis demonstrates that elevated NfL levels may serve as a promising biomarker for diagnosing depressive disorders. Further research on diverse subtypes and longitudinal changes is needed to validate its clinical utility.

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Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis.

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Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS-responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self-assembled into nanoparticles (uhOLN-NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN-NPs to form nanoparticles with hypoxic and ROS responses (HOLN-NPs). Under hypoxia in RGCs, the azo bond of HOLN-NPs breaks and releases uhOLN-NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano-prodrug. The released nicotinamide and oleic acid co-scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN-NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN-NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN-NPs provide a new therapeutic approach for patients with neurodegenerative disease.

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The postmortem diagnosis of diffuse traumatic axonal injury (dTAI) relies on ß-amyloid precursor protein (ß-APP) immunohistochemistry. Most reports of factors associating with dTAI are decades old. We compared background characteristics and neuropathology findings of today's Finnish medico-legal autopsy cases with and without ß-APP-positive dTAI (dTAI+ and dTAI-, respectively). The cases had suffered a head injury prior to death and underwent a full neuropathological examination including ß-APP stain. Background and circumstantial data as well as neuropathology findings were collected from police documents, medical records, and autopsy and neuropathology reports. Prevalence ratios were calculated for each factor to facilitate comparisons between the dTAI+ and dTAI- groups. The dataset comprised 57 cases (66.7% males), with 17 classified as dTAI+ and 40 as dTAI-. Based on prevalence ratios, the factors that had at least two-fold prevalence among dTAI+ cases compared to dTAI- cases were: an unknown injury mechanism; concurrent epidural or subdural haemorrhage; and an accidental manner of death. In contrast, the factors that had at least two-fold prevalence among dTAI- cases compared to dTAI+ cases were: a short postinjury survival (<30 min); concurrent intracerebral/ventricular haemorrhage or contusion; vermal atrophy; and a natural or homicidal manner of death. This study revealed differences in circumstantial features and neuropathology findings between dTAI+ and dTAI- cases in today's medico-legal autopsy material. Data on typical case profiles may help estimate the prior probability of dTAI not only in medico-legal autopsies but also among living patients with head injuries.

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The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.

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The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

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Axonal degeneration is a key component of neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease, and amyotrophic lateral sclerosis. Nicotinamide, an NAD+ precursor, has long since been implicated in axonal protection and reduction of degeneration. However, studies on nicotinamide (NAm) supplementation in humans indicate that NAm has no protective effect. Sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1) regulates several cell responses to axonal damage and has been implicated in promoting neuronal degeneration. SARM1 inhibition seems to result in protection from neuronal degeneration while hydrogen peroxide has been implicated in oxidative stress and axonal degeneration. The effects of laser-induced axonal damage in wild-type and HD dorsal root ganglion cells treated with NAm, hydrogen peroxide (H2O2), and SARM1 inhibitor DSRM-3716 were investigated and the cell body width, axon width, axonal strength, and axon shrinkage post laser-induced injury were measured.

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BACKGROUND: Transverse myelitis is considered one of the cardinal features of neuromyelitis optica spectrum disorder (NMOSD), an immune-mediated inflammatory condition of the CNS characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and spinal cord. We describe a case in which a diagnosis of NMOSD was established, associated with West Nile Virus (WNV) infection. CASE PRESENTATION: A healthy 18-year-old female presented with intractable hiccups and rapidly progressing paraparesis. MRI demonstrated T2 edema extending from the medulla to the conus, consistent with longitudinally extensive transverse myelitis. Serum and CSF Aquaporin-4 IgG (AQP4) were both positive with high titers. In conjunction with antiviral therapy, immunomodulatory treatment was initiated using pulse methylprednisolone, plasmapheresis and Rituximab. A month and a half after admission, the patient was fully ambulatory with no residual symptoms. On her rheumatology follow-up visit, West Nile Virus-specific IgM in CSF was found to be positive from the patient's initial presentation. CONCLUSION: We propose that West Nile Virus may have been the autoimmune trigger to the patient's development of NMOSD, highlighting the importance of evaluating viral triggers in autoimmune diseases.

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The majority of traumatic brain injuries (TBIs), approximately 90%, are classified as mild (mTBIs). Globally, an estimated 4 million injuries occur each year from concussions or mTBIs, highlighting their significance as a public health crisis. TBIs can lead to substantial long-term health consequences, including an increased risk of developing Alzheimer's Disease, Parkinson's Disease (PD), chronic traumatic encephalopathy (CTE), and nearly doubling one's risk of suicide. However, the current management of mTBIs in clinical practice and the available treatment options are limited. There exists an unmet need for effective therapy. This review addresses various aspects of mTBIs based on the most up-to-date literature review, with the goal of stimulating translational research to identify new therapeutic targets and improve our understanding of pathogenic mechanisms. First, we provide a summary of mTBI symptomatology and current diagnostic parameters such as the Glasgow Coma Scale (GCS) for classifying mTBIs or concussions, as well as the utility of alternative diagnostic parameters, including imaging techniques like MRI with diffusion tensor imaging (DTI) and serum biomarkers such as S100B, NSE, GFAP, UCH-L1, NFL, and t-tau. Our review highlights several pre-clinical concussion models employed in the study of mTBIs and the underlying cellular mechanisms involved in mTBI-related pathogenesis, including axonal damage, demyelination, inflammation, and oxidative stress. Finally, we examine a selection of new therapeutic targets currently under investigation in pre-clinical models. These targets may hold promise for clinical translation and address the pressing need for more effective treatments for mTBIs.

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BACKGROUND AND AIMS: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and long-lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench to bedside. Nerve excitability testing (NET) enables to test in vivo axonal properties and can be used to monitor early changes leading to axonal damage. METHODS: We tested NET use in two different CIPN rat models: oxaliplatin (OHP) and paclitaxel (PTX). Animals (female) were chronically treated with either PTX or OHP and compared to respective control animals. NET was performed as soon as the first injection was administered. At the end of the treatment, CIPN onset was verified via a multimodal and robust approach: nerve conduction studies, nerve morphometry, behavioural tests and intraepidermal nerve fibre density. RESULTS: NET showed the typical pattern of axonal hyperexcitability in the 72 h following the first OHP administration, whereas it showed precocious signs of axonal damage in PTX animals. At the end of the month of treatment, OHP animals showed a pattern compatible with a mild axonal sensory polyneuropathy. Instead, PTX cohort was characterised by a rather severe sensory axonal polyneuropathy with minor signs of motor involvement. INTERPRETATION: NET after the first administration demonstrated the ongoing OHP-related channelopathy, whereas in PTX cohort it showed precocious signs of axonal damage. Therefore, NET could be suggested as an early surrogate marker in clinical trials, to detect precocious changes leading to axonal damage.

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BACKGROUND: Up to 30% of patients with Guillain-Barré syndrome require mechanical ventilation and 5% die due to acute complications of mechanical ventilation. There is a considerable group of patients that will need prolonged mechanical ventilation (considered as >14 days) and should be considered for early tracheostomy. The objective of this study is to identify risk factors for prolonged mechanical ventilation. METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with versus without prolonged mechanical ventilation. We considered clinical and electrophysiological characteristics and analyzed factors associated with prolonged mechanical ventilation. RESULTS: Three hundred and three patients were included; 29% required mechanical ventilation. When comparing the groups, patients with prolonged invasive mechanical ventilation (IMV) have a lower score on the Medical Research Council score (19.5 ± 16.2 vs 27.4 ± 17.5, p = 0.03) and a higher frequency of dysautonomia (42.3% vs 19.4%, p = 0.037), as well as lower amplitudes of the distal compound muscle action potential (CMAP) of the median nerve [0.37 (RIQ 0.07-2.25) vs. 3.9 (RIQ1.2-6.4), p = <0.001] and ulnar nerve [0.37 (RIQ0.0-3.72) vs 1.5 (RIQ0.3-6.6), p = <0.001], and higher frequency of severe axonal damage in these nerves (distal CMAP ≤ 1.0 mV). Through binary logistic regression, severe axonal degeneration of the median nerve is an independent risk factor for prolonged IMV OR 4.9 (95%CI 1.1-21.5) p = 0.03, AUC of 0.774, (95%CI 0.66-0.88), p = < 0.001. CONCLUSIONS: Severe median nerve damage is an independent risk factor for prolonged mechanical ventilation.

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BACKGROUND: Among biomarkers of axonal damage, neurofilament light chains (NFL) seem to play a major role, representing a promising and interesting tool in Multiple Sclerosis (MS). Our aim was to explore the predictive role of cerebrospinal fluid (CSF) NFL in patients with a recent diagnosis of MS, naïve to any MS therapy. METHODS: We retrospectively collected data of patients diagnosed with MS, referred to the Neurology Clinic of the University-Hospital G. Rodolico of Catania between January 1st 2005 and December 31st 2015. All patients underwent CSF collection at the time of MS diagnosis and were followed-up for at least three years afterwards. NFL levels were measured in CSF samples with Simoa NFLight advantage kit at the CRESM (University Hospital San Luigi Gonzaga, Orbassano, Torino). NFL levels were expressed as LogNFL. Symbol Digit Modalities test (SDMT) was performed at baseline, at 1-year and at 3-year follow-up. Multivariate logistic regression analysis was performed to investigate LogNFL as a potential risk factor of different clinical outcomes. RESULTS: 244 MS patients (230 relapsing-remitting, RRMS; 94.3 %), with a mean age at diagnosis of 37.0 ± 11.1 years, were recruited. LogNFL did not correlate neither with EDSS score at diagnosis and at subsequent follow-up up to 12 years, nor with SDMT performed at diagnosis, at 1 year and at 3 years. LogNFL were an independent factor for the occurrence of at least one relapse during the first two years after MS diagnosis (OR = 2.75; 95 % CI 1.19-6.31; p = 0.02) and for the occurrence of gadolinium-enhanced (Gd+) lesions during the first 2 years from diagnosis at brain and spine MRI scans (OR = 3.45, 95 % CI 1.81-6.57; p < 0.001). CONCLUSION: The detection of CSF NFL at the time of MS diagnosis can be a useful support to predict the two-year risk of clinical and radiological relapses, thus affecting therapeutic choices in the very early phases of the disease.

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Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1ß levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.

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Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play a vital role in maintaining the integrity of myelin, the protective sheath around nerve fibres essential for efficient signal transmission. However, in MS, oligodendrocytes become dysfunctional, leading to myelin damage and axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction and alterations in glucose and lipid metabolism, contribute significantly to the pathogenesis of MS. Mitochondrial dysfunction is observed in both immune cells and oligodendrocytes within the CNS of MS patients. Impaired mitochondrial function leads to energy deficits, affecting crucial processes such as impulse transmission and axonal transport, ultimately contributing to neurodegeneration. Moreover, mitochondrial dysfunction is linked to the generation of reactive oxygen species (ROS), exacerbating myelin damage and inflammation. Altered glucose metabolism affects the energy supply required for oligodendrocyte function and myelin synthesis. Dysregulated lipid metabolism results in changes to the composition of myelin, affecting its stability and integrity. Importantly, low levels of polyunsaturated fatty acids in MS are associated with upregulated lipid metabolism and enhanced glucose catabolism. Understanding the intricate relationship between these mechanisms is crucial for developing targeted therapies to preserve myelin and promote neurological recovery in individuals with MS. Addressing these metabolic aspects may offer new insights into potential therapeutic strategies to halt disease progression and improve the quality of life for MS patients.

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Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.

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Objective: Primary objective was to retrospectively examine the effects of patient age and carpal tunnel syndrome (CTS) related axon loss on median nerve (MN) high resolution ultrasound (HRUS) in younger and older patients. HRUS parameters evaluated in this study were MN cross sectional area at the wrist (CSA) and wrist-to-forearm ratio (WFR). Methods: The material comprised 467 wrists of 329 patients. The patients were categorized into younger (<65 years) and older (≥65 years) groups. Patients with moderate to extreme CTS were included in the study. Axon loss of the MN was assessed by needle EMG and graded by the interference pattern (IP) density. The association between axon loss and CSA and WFR was studied. Results: The older patients had smaller mean CSA and WFR values compared to the younger patients. CSA correlated positively to the CTS severity only in the younger group. However, WFR correlated positively to CTS severity in both groups. In both age groups, CSA and WFR correlated positively with IP reduction. Conclusions: Our study complemented recent findings on the effects of patient age on the CSA of the MN. However, although the MN CSA did not correlate with the CTS severity in older patients, the CSA increased in respect to the amount of axon loss. Also, as a new result, we presented the positive association of WFR with CTS severity among older patients. Significance: Our study supports the recently speculated need for different MN CSA and WFR cut-off values for younger and older patients in assessing the severity of CTS. With older patients, WFR may be a more reliable parameter to assess the CTS severity than the CSA. CTS related axonal damage of the MN is associated to additional nerve enlargement at the carpal tunnel intel site.

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Background: Optic neuritis (ON) is one of the main neuro-ophthalmic presentations of multiple sclerosis (MS), and it causes optic nerve atrophy and axonal loss. However, so far, there is no effective treatment to improve long-term outcomes. Methods: In a double-blind placebo-controlled randomized clinical trial, 50 patients with MS-related ON were allocated into two arms (24 in the control group and 26 in the intervention group) receiving either 25000IU retinyl palmitate or an identical placebo for six months. Visual evoked potential (VEP), visual acuity, and the retinal nerve fiber layer (RNFL) thickness were evaluated and compared before and after the treatment. Results: RNFL thickness reduction in the affected eyes at sixth month compared to the baseline were 14.81 and 19.46 µm, in the intervention and control groups, respectively (P=0.017). However, VitA therapy did not affect visual acuity and VEP. Conclusion: Vitamin A supplementation in the patients with acute ON in MS could lessen optic nerve axonal loss.

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease associated with axonal injury, and neurofilament light chains in serum (sNfL) are considered a biomarker for this damage. We aimed to investigate the relationship between sNfL and the axonal damage in early MS lesions in a special cohort of biopsied patients. sNfL from 106 biopsied patients with 26 follow-up samples were analyzed using single-molecule array (SiMoA) technology. Findings were correlated with clinical parameters and histological findings of acute axonal damage (APP-positive spheroids) and axonal loss in different lesion stages. A median of 59 pg/ml sNfL was found (range 8-3101 pg/ml). sNfL levels correlated with APP-positive spheroids in early active demyelinating lesions that represent the earliest lesion stages (p < 0.01). A significant negative correlation between sNfL levels in follow-up blood samples and axonal density in normal-appearing white matter was also observed (p = 0.02). sNfL levels correlated with the Expanded Disability Status Score at biopsy (p < 0.01, r = 0.49) and at last clinical follow-up (p < 0.01, r = 0.66). In conclusion, sNfL likely represent a compound measure of recent and ongoing neuroaxonal damage. We found that sNfL in biopsied MS patients correlate with acute axonal damage in the earliest MS lesion stages. Determination of sNfL levels thus allows insight into brain pathology and underlines the relevance of relapse-associated lesional pathology. Axonal loss in normal-appearing white matter contributes to sNfL levels independent of relapses. Since sNfL levels correlate with clinical disability, they may predict the future disability of patients and help with individual treatment decisions.

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OBJECTIVE: Ischaemic stroke has a high death rate and frequently results in long-term and severe brain damage in survivors. miRNA-124-3p (miR-124-3p) treatment has been suggested to reduce ischaemia and play a vital function in avoiding neuron death. An investigation of the role of miR-124-3p, in the ischaemia damage repair or protection in the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/R) model, was the purpose of this research. METHODS: The expression of miRNA and mRNA in the MCAO model was predicted using bioinformatics analysis. The OGD/R neuronal model was developed. We examined the influence of a number of compounds on the OGD/R model in vitro using gain- and loss-of-function approaches. RESULTS: For starters, miR-124-3p and Nrep level in the MCAO model were found to be lower in the model predicted by bioinformatics than in the sham-operated group. And then in the OGD/R model, miR-124-3p treatment reduced OGD/R neuronal damage, increased neuronal survival, and reduced apoptosis in cell lines. Moreover, we further looked at the impact of miR-124-3p on downstream Rnf38 and Nrep using the OGD/R model. Western blot analysis and dual-luciferase reporter assays indicated that miR-124-3p binds and inhibits Rnf38. Finally, although Nrep expression was reduced in the OGD/R model neuronal model, it was shown that miR-124-3p administration reduced apoptosis and increased neuronal activity, particularly with regard to axon regeneration-related proteins. CONCLUSION: Our studies have shown that miR-124-3p may reduce neuronal injury by preventing Rnf38-mediated effects on the Nrep axis.

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Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.