Search Results (73)

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by wide phenotypic heterogeneity. Despite efforts to carefully define and stratify ALS patients according to their clinical and genetic features, prognosis prediction still remains unreliable. Biomarkers that reflect changes in the central nervous system would be useful, but the physical impossibility of direct sampling and analysis of the nervous system makes them challenging to validate. A highly explored option is the identification of neuronal-specific markers that could be analyzed in peripheral biofluids. This review focuses on the description of the physical and biological barriers to the central nervous system and of the composition of biofluids in which ALS disease biomarkers are actively searched. Finally, we comment on already validated biomarkers, such as the neurofilament light chain, and show the potential of extracellular vesicles (EVs) and cell-free DNA as additional biomarkers for disease prediction. Full article

Spinal cord injury (SCI) is a prevalent central nervous system disorder that causes significant disability and mortality. Unfortunately, due to the complex pathophysiological mechanisms involved, there remains a critical paucity of effective therapeutic interventions capable of achieving neural tissue regeneration and functional recovery enhancement in SCI patients. The advancements in extracellular vesicles (EVs) as a cell-free therapy for SCI have displayed notable benefits. These include their small size, low immunogenicity, capacity to target specific areas, and ability to cross the blood‒brain barrier (BBB). EVs offer the potential to not only repair tissue damage and stimulate regeneration but also effectively deliver and release them at the site of SCI when combined with diverse biomaterials. This review explores the biological role and importance of EVs in treating SCI, highlighting the combined use of modified EVs with different biomaterials and their potential for future applications. It presents new and hopeful treatment approaches for individuals afflicted with SCI. Full article

Background: Severe spinal cord injury (SCI) represents a debilitating condition with long-term physical and socioeconomic impacts. Understanding the pathophysiology of SCI and therapeutic interventions such as decompressive laminectomy and expansive duraplasty is crucial for optimizing patient outcomes. Objective: This systematic review explores the pathophysiology of SCI and evaluates evidence linking decompressive laminectomy and duraplasty to improved neuroplasticity and recovery. Methods: A comprehensive search was conducted in PubMed, Web of Science, and Cochrane Library for studies on decompressive surgery in SCI. Inclusion criteria were original articles investigating pathophysiology, neuroplasticity mechanisms, or surgical outcomes. Data on pathophysiological changes, molecular markers, and functional outcomes were extracted. Results: From 1240 initial articles, 43 studies were included, encompassing both animal models and human clinical data. Findings highlighted the role of inflammatory cascades, blood–spinal cord barrier disruption, and neurotrophic factor modulation in recovery. Decompressive duraplasty was associated with improved intrathecal pressure (ITP) management and neuroplasticity markers, such as BDNF and GAP-43. Conclusions: This review underscores the therapeutic potential of decompressive laminectomy and duraplasty in SCI. While evidence suggests benefits in promoting neuroplasticity, further research is needed to elucidate molecular mechanisms and refine interventions. Full article

Background: Neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, and spinal cord injury (SCI) are significant global health challenges due to their complex pathology and limited therapeutic options. Conventional treatments often fail to efficiently cross the blood–brain barrier (BBB), leading to poor bioavailability and systemic toxicity. This narrative review explores the potential of nanomedicine in addressing these limitations and advancing targeted therapies for neural disorders. Methods: This review examines recent studies on the use of engineered nanoparticles (NPs), including liposomes, dendrimers, micelles, and nanogels, for targeted drug delivery and multifunctional theranostics in neural diseases. It evaluates their role in promoting axon regeneration, reducing neuroinflammation, and repairing neural damage. Additionally, innovative applications in gene therapy and RNA-based treatments, such as CRISPR-Cas9 and RNA interference (RNAi), are discussed. Challenges related to toxicity, scalability, affordability, and regulatory barriers are highlighted, along with potential strategies to address these issues. Results: Nanoparticles have shown significant promise in crossing the BBB, delivering therapeutic agents to neural tissues, and minimizing off-target effects. Emerging applications in gene and RNA-based therapies demonstrate their versatility in addressing disease-specific challenges. However, unresolved issues such as long-term safety, manufacturing scalability, and cost continue to pose challenges. Conclusions: Nanomedicine offers a promising approach to overcoming current limitations in the treatment of neural disorders. This review emphasizes the need for continued interdisciplinary efforts to address translational barriers and highlights the potential for nanomedicine to improve the outcomes and quality of life for patients with neural disorders, stroke, and SCI. Full article

Meningitis is the acute or chronic inflammation of the protective membranes, surrounding the brain and spinal cord, and this inflammatory process spreads throughout the subarachnoid space. The traditional drug delivery methods pose a disadvantage in limiting the capacity of crossing the blood–brain barrier (BBB) to reach the central nervous system (CNS). Hence, it is imperative to develop novel approaches that can overcome these constraints and offer efficient therapy for meningitis. Nanoparticle (NP)-based therapeutic approaches have the potential to address the limitations such as penetrating the BBB and achieving targeted drug release in specific cells and tissues. This review highlights recent advancements in nanotechnology-based approaches, such as functionalized polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers, nanoemulsions, liposomes, transferosomes, and metallic NPs for the treatment of meningitis. Recently, bionics has emerged as a next-generation technology in the development of novel ideas from biological principles, structures, and interactions for neurological and neuroinfectious diseases. Despite their potential, more studies are needed to ensure the safety and efficacy of NP-based drug delivery systems focusing on critical aspects such as toxicity, immunogenicity, and pharmacokinetics. Therefore, this review addresses current treatment strategies and innovative nanoparticle approaches, and it discusses future directions for efficient and targeted meningitis therapies. Full article

Spinal cord injury (SCI) disrupts the blood–spinal cord barrier (BSCB) exacerbating damage by allowing harmful substances and immune cells to infiltrate spinal neural tissues from the vasculature. This leads to inflammation, oxidative stress, and impaired axonal regeneration. The BSCB, essential for maintaining spinal cord homeostasis, is structurally similar to the blood–brain barrier. Its restoration is a key therapeutic target for improving outcomes in SCI. Mesenchymal stromal/stem cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have gained attention for their regenerative, immunomodulatory, and anti-inflammatory properties in promoting BSCB repair. MSCs enhance BSCB integrity by improving endothelial–pericyte association, restoring tight junction proteins, and reducing inflammation. MSC-EVs, which deliver bioactive molecules, replicate many of MSCs’ therapeutic effects, and offer a promising cell-free alternative. Preclinical studies have shown that both MSCs and MSC-EVs can reduce BSCB permeability, promote vascular stability, and support functional recovery. While MSC therapy is advancing in clinical trials, MSC-EV therapies require further optimization in terms of production, dosing, and delivery protocols. Despite these challenges, both therapeutic approaches represent significant potential for treating SCI by targeting BSCB repair and improving patient outcomes. Full article

This review aims to address the significant challenges of treating central nervous system (CNS) disorders such as neurodegenerative diseases, strokes, spinal cord injuries, and brain tumors. These disorders are difficult to manage due to the complexity of disease mechanisms and the protective blood–brain barrier (BBB), which restricts drug delivery. Recent advancements in nanoparticle (NP) technologies offer promising solutions, with potential applications in drug delivery, neuroprotection, and neuroregeneration. By examining current research, we explore how NPs can cross the BBB, deliver medications directly to targeted CNS regions, and enhance both diagnostics and treatment. Key NP strategies, such as passive targeting, receptor-mediated transport, and stimuli-responsive systems, demonstrate encouraging results. Studies show that NPs may improve drug delivery, minimize side effects, and increase therapeutic effectiveness in models of Alzheimer’s, Parkinson’s, stroke, and glioblastoma. NP technologies thus represent a promising approach for CNS disorder management, combining drug delivery and diagnostic capabilities to enable more precise and effective treatments that could significantly benefit patient outcomes. Full article

Individuals with spinal cord injury (SCI) experience an increased risk for obesity and cardiometabolic disease. Recommendations to prevent and treat obesity for those with SCI follow those of the US Department of Agriculture to adopt a healthy eating pattern that includes eating a variety of fruits, vegetables, grains, dairy, and protein, plus limiting added sugars, saturated fats, and sodium. Yet, people with SCI eat too many calories, fat, and carbohydrates and too few fruits, vegetables, and whole grains. The study is based on secondary analyses of SCI participants (n = 122) who enrolled in a weight loss study to determine how SCI may impact their ability to prepare food at home. We hypothesize those with higher-level spinal injuries (specifically, those with cervical versus those with thoracic or lumbar/sacral injuries) experience significantly greater difficulty and are more likely to rely on others’ assistance to perform meal preparation tasks. Physiologic (weight, BMI, blood pressure, hemoglobin A1c) and self-reported data (demographic plus responses to the Life Habits Short Survey and meal prep items) were collected at baseline and qualitative data were obtained from a subsample after the intervention during phone interviews. Participants’ average age was 50 ± 14.7 years old, they lived with SCI for an average of 13.0 ± 13.1 years, and their average BMI was 32.0 ± 6.5. Participants were predominantly white (76.1%) men (54.1%) who had some college education (76.3%), though only 28.8% worked. A substantial proportion of respondents (30% to 68%) reported difficulty across the 13 tasks related to purchasing and preparing meals, with a proxy reported as the most common assistance type used across all tasks (17% to 42%). Forty-nine percent reported difficulty preparing simple meals, with 29% reporting a proxy does the task. More than half reported difficulty using the oven and stove, though between 60% to 70% reported no difficulty using other kitchen appliances (e.g., coffee machine, food processor, can opener), the refrigerator, or microwave. There was a significant difference in kitchen function by injury level. Those living with cervical-level injuries had significantly greater limitations than those with thoracic-level injuries. Spouses, other family members, and caregivers were most likely to serve as proxies and these individuals exerted both positive and negative influences on respondents’ dietary intake, based on qualitative data obtained during interviews. The results suggest that many people living with SCI experience functional and environmental barriers that impact their ability to prepare food and use kitchen appliances. Future research should examine how SCI-related functional limitations, transportation access, accessibility of the kitchen, ability to use appliances, availability of financial resources, and assistance by others to prepare foods impact people’s ability to follow a healthy eating pattern. Full article

Spinal cord injury (SCI) often results in permanent loss of motor and sensory function. After SCI, the blood–spinal cord barrier (BSCB) is disrupted, causing the infiltration of neutrophils and macrophages, which secrete several kinds of cytokines, as well as matrix metalloproteinases (MMPs). MMPs are proteases capable of degrading various extracellular matrix (ECM) proteins, as well as many non-matrix substrates. The tissue inhibitor of MMPs (TIMP)-1 is significantly upregulated post-SCI and operates via MMP-dependent and MMP-independent pathways. Through the MMP-dependent pathway, TIMP-1 directly reduces inflammation and destruction of the ECM by binding and blocking the catalytic domains of MMPs. Thus, TIMP-1 helps preserve the BSCB and reduces immune cell infiltration. The MMP-independent pathway involves TIMP-1’s cytokine-like functions, in which it binds specific TIMP surface receptors. Through receptor binding, TIMP-1 can stimulate the proliferation of several types of cells, including keratinocytes, aortic smooth muscle cells, skin epithelial cells, corneal epithelial cells, and astrocytes. TIMP-1 induces astrocyte proliferation, modulates microglia activation, and increases myelination and neurite extension in the central nervous system (CNS). In addition, TIMP-1 also regulates apoptosis and promotes cell survival through direct signaling. This review provides a comprehensive assessment of TIMP-1, specifically regarding its contribution to inflammation, ECM remodeling, and scar formation after SCI. Full article

Spinal cord injury is a complicated medical condition both from the clinician’s point of view in terms of management and from the patient’s perspective in terms of unsatisfactory recovery. Depending on the severity, this disorder can be devastating despite the rapid and appropriate use of modern imaging techniques and convenient surgical spinal cord decompression and stabilization. In this context, there is a mandatory need for novel adjunctive therapeutic approaches to classical treatments to improve rehabilitation chances and clinical outcomes. This review offers a new and original perspective on therapies targeting the microglia, one of the most relevant immune cells implicated in spinal cord disorders. The first part of the manuscript reviews the anatomical and pathophysiological importance of the blood-spinal cord barrier components, including the role of microglia in post-acute neuroinflammation. Subsequently, the authors present the emerging therapies based on microglia modulation, such as cytokines modulators, stem cell, microRNA, and nanoparticle-based treatments that could positively impact spinal cord injury management. Finally, future perspectives and challenges are also highlighted based on the ongoing clinical trials related to medications targeting microglia. Full article

The treatment of spinal cord injury (SCI) is often ineffective. Additionally, SCI-induced inflammation leads to secondary injury. Current anti-inflammatory hydrophilic drugs fail to reach the nerve injury site due to the blood–brain barrier. Here, we synthesized MSR405, a new lipophilic unsaturated fatty acid derivative of Radix Isatidis and investigated its therapeutic effect in SCI model rats. Furthermore, we systematically investigated its structure, toxicity, anti-inflammatory effect, and the underlying mechanism. MSR405 was injected into the abdominal cavity of the Sprague Dawley SCI model rats, and the effect on their behavioral scores and pathology was estimated to assess the status of neurological inflammation. Our data show that MSR405 treatment significantly improved the motor function of SCI rats, and markedly suppressed the associated neuroinflammation. Moreover, MSR405 could attenuate LPS-induced inflammatory response in BV2 cells (Mouse microglia cells) in vitro. Mechanistically, MSR405 inhibits proinflammatory cytokines, supporting the anti-inflammatory response. Additionally, MSR405 can significantly block the TLR4/NF-κB signaling pathway and nitric oxide production. In summary, MSR405 reduces inflammation in SCI rats through the TLR4/NF-κB signal cascade and can inhibit neuroinflammation after spinal cord injury. Full article

Meningitis is an inflammatory condition affecting the meninges surrounding the brain and spinal cord. Meningitis can be triggered by various factors, including infectious agents like viruses and bacteria and non-infectious contributors such as cancer or head injuries. The impact of meningitis on the central nervous system involves disruptions in the blood–brain barrier, cellular infiltrations, and structural alterations. The clinical features that differentiate between tuberculous meningitis (TBM) and non-tuberculous meningitis (NTM) are discussed in this review and aid in accurate diagnosis. The intricate interplay of reactive oxygen species, ferroptosis, and reactive nitrogen species within the central nervous system reveals a promising field of research for innovative therapeutic strategies tailored to TBM. This review highlights the alternative treatments targeting oxidative stress-induced TBM and ferroptosis, providing potential avenues for intervention in the pathogenesis of this complex condition. Full article

Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood–brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using ⁶⁴Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p. Full article

Cell-to-cell communication is essential for the appropriate development and maintenance of homeostatic conditions in the central nervous system. Extracellular vesicles have recently come to the forefront of neuroscience as novel vehicles for the transfer of complex signals between neuronal cells. Extracellular vesicles are membrane-bound carriers packed with proteins, metabolites, and nucleic acids (including DNA, mRNA, and microRNAs) that contain the elements present in the cell they originate from. Since their discovery, extracellular vesicles have been studied extensively and have opened up new understanding of cell–cell communication; they may cross the blood–brain barrier in a bidirectional way from the bloodstream to the brain parenchyma and vice versa, and play a key role in brain–periphery communication in physiology as well as pathology. Neurons and glial cells in the central nervous system release extracellular vesicles to the interstitial fluid of the brain and spinal cord parenchyma. Extracellular vesicles contain proteins, nucleic acids, lipids, carbohydrates, and primary and secondary metabolites. that can be taken up by and modulate the behaviour of neighbouring recipient cells. The functions of extracellular vesicles have been extensively studied in the context of neurodegenerative diseases. The purpose of this review is to analyse the role extracellular vesicles extracellular vesicles in central nervous system cell communication, with particular emphasis on the contribution of extracellular vesicles from different central nervous system cell types in maintaining or altering central nervous system homeostasis. Full article

Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules, which orchestrate essential biological processes, including cell differentiation, proliferation, and survival, in the recipient cells. These bioactive properties of exosomes render them a promising choice for therapeutic use in the realm of tissue regeneration and repair. Exosomes possess notable positive attributes, including a high bioavailability, inherent safety, and stability, as well as the capacity to be functionalized so that drugs or biological agents can be encapsulated within them or to have their surface modified with ligands and receptors to imbue them with selective cell or tissue targeting. Remarkably, their small size and capacity for receptor-mediated transcytosis enable exosomes to cross the blood–brain barrier (BBB) and access the central nervous system (CNS). Unlike cell-based therapies, exosomes present fewer ethical constraints in their collection and direct use as a therapeutic approach in the human body. These advantageous qualities underscore the vast potential of exosomes as a treatment option for neurological injuries and diseases, setting them apart from other cell-based biological agents. Considering the therapeutic potential of exosomes, the current review seeks to specifically examine an area of investigation that encompasses the development of Schwann cell (SC)-derived exosomal vesicles (SCEVs) as an approach to spinal cord injury (SCI) protection and repair. SCs, the myelinating glia of the peripheral nervous system, have a long history of demonstrated benefit in repair of the injured spinal cord and peripheral nerves when transplanted, including their recent advancement to clinical investigations for feasibility and safety in humans. This review delves into the potential of utilizing SCEVs as a therapy for SCI, explores promising engineering strategies to customize SCEVs for specific actions, and examines how SCEVs may offer unique clinical advantages over SC transplantation for repair of the injured spinal cord. Full article