Reviews in the Neurosciences最新文献

Epilepsy is a group of chronic neurological brain disorders characterized by recurrent spontaneous unprovoked seizures, which are accompanied by significant neurobiological, cognitive, and psychosocial impairments. With a global prevalence of approximately 0.5-1 % of the population, epilepsy remains a serious public health concern. Despite the development and widespread use of over 20 anticonvulsant drugs, around 30 % of patients continue to experience drug-resistant seizures, leading to a substantial reduction in quality of life and increased mortality risk. Given the limited efficacy of current treatments, exploring new therapeutic approaches is critically important. In recent years, Gi-protein-coupled receptors, particularly cannabinoid receptors CB1 and CB2, have garnered increasing attention as promising targets for the treatment seizures and prevention of epilepsy. Emerging evidence suggests a significant role of the cannabinoid system in modulating neuronal activity and protecting against hyperexcitability, underscoring the importance of further research in this area. This review provides up-to-date insights into the pathogenesis and treatment of epilepsy, with a special focus on the role of the cannabinoid system, highlighting the need for continued investigation to develop more effective therapeutic strategies.

Vault RNAs (vtRNAs) are a novel group of non-coding RNAs that are involved in various signaling mechanisms. vtRNAs are joined by three proteins major vault protein (MVP), vault poly (ADP-ribose) polymerase (VPARP), and telomerase-associated protein 1 (TEP1) to form the vault complex. In humans, only four vtRNA including vtRNA 1-1, vtRNA 1-2, vtRNA 1-3, vtRNA 2-1) have been discovered. In nerve cells, vtRNA is involved in synapse formation through MAPK signaling. vtRNA travels to the distal area of neurites as a key unit in the vault complex. Moreover, tRNA is detached from the vault complex in the neurite via a mitotic kinase Aurora-A-reliant MVP phosphorylation. Several molecules contribute to the formation of vtRNAs. For instance, SRSF2 and NSUN2 and their attachment to vtRNA1-1 determines the production of small-vtRNAs. Through the same factors, vtRNAs could play a role in neurodevelopmental deficits. Addition the role of vtRNA expression and vault proteins has been recently studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as well as brain cancers. While the mechanisms of vtRNA involvement in neurological disorders is not well-demonstrated, we believe this could be related to the impact of vtRNA regulation in autophagy, immunoregulation, RNA stability, cellular stress, apoptosis, and regulation of other epigenetic pathways. The present review captures the state-of-the-art regarding the role of vtRNAs in neurodevelopment, normal nervous system function, and neurological disorders.

The brain is a highly plastic organ that continually receives and integrates signals to generate functional and structural changes and homeostatic adaptations throughout life. Alterations in some signaling pathways that mediate these responses can impact brain plasticity, accelerate brain aging and potentially lead to neurodegeneration. There is substantial evidence that two important signaling pathways activated by neurotrophins, nonacronymic (VGF) and brain-derived neurotrophic factor (BDNF), are involved in substantial functions stimulating neuronal growth, differentiation, and circuit establishment during development and neuronal maintenance and plasticity in the mature brain. In this review, we present evidence that these two pathways and their interactions are central players in cognitive performance and alterations in pathological aging, particularly in conditions such as Alzheimer's disease (AD). Finally, we suggest specific avenues for future research on the basis of recent findings suggesting these molecules are diagnostic biomarkers and putative therapeutic tools to prevent, delay or improve AD neuropathology.

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by deficits in social relationships and communication and restrictive, repetitive behaviors and interests. ASDs form a heterogeneous group from a clinical and genetic perspective. Currently, ASDs diagnosis is based on the clinical observation of the individual's behavior. The subjective nature of behavioral diagnoses, in the context of ASDs heterogeneity, contributes to significant variation in the age at ASD diagnosis. Early detection has been proved to be critical in ASDs, as early start of appropriate therapeutic interventions greatly improve the outcome for some children. Structural magnetic resonance imaging (MRI) is widely used in the diagnostic work-up of neurodevelopmental conditions, including ASDs, mostly for brain malformations detection. Recently, the focus of brain imaging shifted towards quantitative MRI parameters, aiming to identify subtle changes that may establish early detection biomarkers. ASDs have a strong genetic component; deletions and duplications of several genomic loci have been strongly associated with ASDs risk. Consequently, a multitude of neuroimaging and genetic findings emerged in ASDs in the recent years. The association of gross or subtle changes in brain morphometry and volumes with different genetic defects has the potential to bring new insights regarding normal development and pathomechanisms of various disorders affecting the brain. Still, the clinical implications of these discoveries and the impact of genetic abnormalities on brain structure and function are unclear. Here we review the literature on brain imaging correlated with the most prevalent genomic imbalances in ASD, and discuss the potential clinical impact.

Intracranial atherosclerotic disease (ICAD) significantly increases the risk of ischemic stroke. It involves the accumulation of plaque within arterial walls and narrowing or blockage of blood vessel lumens. Accurate imaging is crucial for the diagnosis and management of ICAD at both acute and chronic stages. However, imaging the small, tortuous intracranial arterial walls amidst complex structures is challenging. Clinicians have employed diverse approaches to improve imaging quality, with a particular emphasis on optimizing the acquisition of images using new techniques, enhancing spatial and temporal resolution of images, and refining post-processing techniques. ICAD imaging has evolved from depicting lumen stenosis to assessing blood flow reserve and identifying plaque components. Advanced techniques such as fractional flow reserve (FFR), high-resolution vessel wall magnetic resonance (VW-MR), optical coherence tomography (OCT), and radial wall strain (RWS) now allow direct visualization of flow impairment, vulnerable plaques, and blood flow strain to plaque, aiding in the selection of high-risk stroke patients for intervention. This article reviews the progression of imaging modalities from lumen stenosis to vessel wall pathology and compares their diagnostic value for risk stratification in ICAD patients.

Peripheral nerve injury, resulting from various physical and chemical causes, has a high incidence and significant functional impact. This injury, affecting both sensory and motor functions, can severely diminish quality of life and cause mental health issues. Consequently, it is a major focus of current research. Recent advancements in peripheral nerve repair technology, including the application of new techniques and materials, have expanded the options for nerve repair methods. A comprehensive article that combines the pathological process of peripheral nerve repair with these methods is needed to advance research in this field. This review aims to provide a comprehensive overview of various techniques for repairing peripheral nerve injuries. Beginning with the histopathology of nerve injury, it evaluates these techniques in detail to offer clinical guidance. This review summarizes the advantages and disadvantages of various peripheral nerve repair methods, including photobiological modulation therapy, suture repair, nerve graft repair, vein graft catheter repair, muscle graft repair, laser welding repair, nerve catheter repair, nerve sliding repair technology, growth factor-assisted repair, stem cell therapy, and exosome therapy. Additionally, it explores future directions in the treatment of peripheral nerve injuries, providing valuable references for experimental research and clinical treatment.

Glioblastoma is a brain cancer with a poor prognosis. Failure of classical chemotherapy and surgical treatments indicates that new therapeutic approaches are needed. Among cell-free options, exosomes are versatile extracellular vesicles (EVs) that carry important cargo across barriers such as the blood-brain barrier (BBB) to their target cells. This makes exosomes an interesting option for the treatment of glioblastoma. Moreover, exosomes can comprise many therapeutic cargos, including lipids, proteins, and nucleic acids, sampled from special intercellular compartments of their origin cell. Cells exposed to various immunomodulatory stimuli can generate exosomes enriched in specific therapeutic molecules. Notably, the secretion of exosomes could modify the immune response in innate and adaptive immune systems. For instance, glioblastoma-associated exosomes (GBex) uptake by macrophages could influence macrophage dynamics (e.g., shifting CD markers expression). Expression of critical immunoregulatory proteins such as cytotoxic T-lymphocyte antigen-1 (CTLA1) and programmed death-1 (PD-1) on GBex indicates the direct crosstalk of these nano-size vesicles with the immune system. The present study reviews the role of exosomes in immune system cells, including B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs), as well as novel technologies in the field.

The effectiveness of the support stimulation of the mechanoreceptors of the feet has been first shown in space medicine. In space flight during support withdrawal with non-use of postural muscle, this method is a countermeasure against sensorimotor disorders. Later, it was applied in clinical practice as treatment of motor disorders after stroke, in Parkinson's disease, infantile cerebral palsy, neuropathies, and many others. The impact of such stimulation on motor control is due to spinal and supraspinal mechanisms, which are activated by creating an additional support afferent input through the plantar surface. Many studies confirmed the positive effect of support stimulation on motor control, but the protocols of such stimulation remain the subject of active discussion. This review includes (1) the features of sensitivity of the foot sole cutaneous afferents to the support mechanical stimuli, (2) data on spinal and supraspinal responses of the nervous system to support stimulation, and (3) the results of applying this approach in neurological practice via various techniques. Summarizing this information, the authors highlight the most promising ways and types of medical devices for foot support stimulation in neurology.

Migraine is a multidimensional disease affecting a large portion of the human population presenting with a variety of symptoms. In the era of personalized medicine, successful migraine treatment presents a challenge, as several studies have shown the impact of a patient's genetic profile on therapy response. However, with the emergence of contemporary treatment options, there is promise for improved outcomes. A literature search was conducted in PubMed and Scopus, in order to obtain studies investigating the impact of genetic factors on migraine therapy outcome. Overall, 23 studies were included in the current review, exhibiting diversity in the treatments used and the genetic variants investigated. Divergent genes were assessed for each category of migraine treatment. Several genetic factors were identified to contribute to the heterogeneous response to treatment. SNPs related to pharmacodynamic receptors, pharmacogenetics and migraine susceptibility loci were the most investigated variants, revealing some interesting significant results. To date, various associations have been recorded correlating the impact of genetic factors on migraine treatment responses. More extensive research needs to take place with the aim of shedding light on the labyrinthine effects of genetic variations on migraine treatment, and, consequently, these findings can promptly affect migraine treatment and improve migraine patients' life quality in the vision of precise medicine.

The prevalence of stroke and traumatic brain injury is increasing worldwide. However, current treatments do not fully cure or stop their progression, acting mostly on symptoms. Amphetamine and methylphenidate are stimulants already approved for attention deficit hyperactivity disorder and narcolepsy treatment, with neuroprotective potential and benefits when used in appropriate doses. This review aimed to summarize pre-clinical and clinical trials testing either amphetamine or methylphenidate for the treatment of stroke and traumatic brain injury. We used PubMed as a database and included the following keywords ((methylphenidate) OR (Ritalin) OR (Concerta) OR (Biphentin) OR (amphetamine) OR (Adderall)) AND ((stroke) OR (brain injury) OR (neuroplasticity)). Overall, studies provided inconsistent results regarding cognitive and motor function. Neurite outgrowth, synaptic proteins, dendritic complexity, and synaptic plasticity increases were reported in pre-clinical studies along with function improvement. Clinical trials have demonstrated that, depending on the brain region, there is an increase in motor activity, attention, and memory due to the stimulation of the functionally depressed catecholamine system and the activation of neuronal remodeling proteins. Nevertheless, more clinical trials and pre-clinical studies are needed to understand the drugs' full potential for their use in these brain diseases namely, to ascertain the treatment time window, ideal dosage, long-term effects, and mechanisms, while avoiding their addictive potential.