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Background: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction. Methods: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Results: In view of recent evidence that the gut–brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut–brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut–brain axis homeostasis towards local and systemic pro-inflammatory responses. Conclusion: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors (ICIs) for the treatment of various advanced and aggressive types of malignancy has significantly increased both survival and long-term remission rates. ICIs block crucial inhibitory pathways of the immune system, in order to trigger an aggravated immune response against the tumor. However, this enhanced immune activation leads to the development of numerous immune-related adverse events (irAEs), which may affect any system. Although severe neurological irAEs are relatively rare, they carry a high disability burden, and they can be potentially life-threatening. Therefore, clinicians must be alert and act promptly when individuals receiving ICIs present with new-onset neurological symptoms. In this narrative review, we have collected all the currently available data regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of post-ICI neurological irAEs. This review aims to raise physicians' awareness, enrich their knowledge regarding disease pathogenesis, and guide them through the diagnosis and management of post-ICI neurological irAEs. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells' reactive phenotype. [ABSTRACT FROM AUTHOR]

Stress-related mental disorders have become increasingly prevalent, thus endangering mental health worldwide. Exploring stress-associated brain alterations is vital for understanding the possible neurobiological mechanisms underlying these changes. Based on existing evidence, the brain endogenous cannabinoid system (ECS) plays a significant role in the stress response, and disruptions in its function are associated with the neurobiology of various stress-related disorders. This study primarily focuses on investigating the impact of chronic unpredictable stress (CUS) on the expression of hippocampal cannabinoid type 1 (CB1) receptors, part of the ECS, in adult male and female Wistar rats. Additionally, it explores whether environmental enrichment (EE) initiated during adolescence could mitigate the CUS-associated alterations in CB1 expression. Wistar rats, shortly after weaning, were placed in either standard housing (SH) or EE conditions for a duration of 10 weeks. On postnatal day 66, specific subgroups of SH or EE animals underwent a 4-week CUS protocol. Western blot (WB) analysis was conducted in the whole hippocampus of the left brain hemisphere to assess total CB1 protein expression, while immunohistochemistry (IHC) was performed on the right hemisphere to estimate the expression of CB1 receptors in certain hippocampal areas (i.e., CA1, CA3 and dentate gyrus-DG). The WB analysis revealed no statistically significant differences in total CB1 protein levels among the groups; however, reduced CB1 expression was found in specific hippocampal sub-regions using IHC. Specifically, CUS significantly decreased CB1 receptor expression in the CA1 and DG of both sexes, whereas in CA3 the CUS-associated decrease was limited to SH males. Interestingly, EE housing proved protective against these reductions. These findings suggest a region and sex-specific endocannabinoid response to chronic stress, emphasizing the role of positive early experiences in the protection of the adolescent brain against adverse conditions later in life. [ABSTRACT FROM AUTHOR]

The development and further optimization of the diagnostic criteria for multiple sclerosis (MS) emphasize the establishment of an early and accurate diagnosis. So far, numerous studies have revealed the significance of early treatment administration for MS and its association with slower disease progression and better late outcomes of the disease with regards to disability accumulation. However, according to current research results, both neuroinflammatory and neurodegenerative processes may exist prior to symptom initiation. Despite the fact that a significant proportion of individuals with radiologically isolated syndrome (RIS) progress to MS, currently, there is no available treatment approved for RIS. Therefore, our idea of "early treatment administration" might be already late in some cases. In order to detect the individuals who will progress to MS, we need accurate biomarkers. In this review, we present notable research results regarding the underlying pathology of MS, as well as several potentially useful laboratory and neuroimaging biomarkers for the identification of high-risk individuals with RIS for developing MS. This review aims to raise clinicians' awareness regarding "subclinical" MS, enrich their understanding of MS pathology, and familiarize them with several potential biomarkers that are currently under investigation and might be used in clinical practice in the future for the identification of individuals with RIS at high risk for conversion to definite MS. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis (EAE) is a basic and reliable model used to study clinical and pathological hallmarks of multiple sclerosis (MS) in rodents. Several studies suggest neural precursor cells (NPCs) as a significant research tool while reporting that transplanted NPCs are a promising therapeutic approach to treating neurological disorders, such as MS. The main objective was to approach a preclinical, in vivo scenario of oligodendrogenesis with NPCs, targeting the main chronic demyelinated lumbosacral milieu of EAE, via the least invasive delivery method which is lumbar puncture. We utilized MOG35‐55 peptide to induce EAE in C57BL/6 mice and prior to the acute relapse, we intervened with either the traceable GFP+ cellular therapy or saline solution in the intrathecal space of their lumbar spine. A BrdU injection, which enabled us to monitor endogenous proliferation, marked the endpoint 50 days post‐induction (50 dpi). Neuropathology with high‐throughput, triple immunofluorescent, and transmission electron microscopy (TEM) data were extracted and analyzed. The experimental treatment attenuated the chronic phase of EAE (50 dpi; score <1) following an acute, clinical relapse. Myelination and axonal integrity were rescued in the NPC‐treated animals along with suppressed immune populations. The differentiation profile of the exogenous NPCs and endogenous BrdU+ cells was location‐dependent where GFP+‐rich areas drove undifferentiated phenotypes toward the oligodendrocyte lineage. In situ oligodendrocyte enrichment was demonstrated through increased (p < 0.001) gap junction channels of Cx32 and Cx47, reliable markers for proliferative oligodendroglia syncytium. TEM morphometric analysis ultimately manifested an increased g‐ratio in lumbosacral fibers of the recovered animals (p < 0.001). Herein, we suggest that a single, lumbar intrathecal administration of NPCs capacitated a viable cellular load and resulted in clinical and pathological amelioration, stimulating resident OPCs to overcome the remyelination failure in EAE demyelinating locale. [ABSTRACT FROM AUTHOR]