Potential therapeutic and diagnostic approaches of exosomes in multiple sclerosis pathophysiology.

Exosomes are bilayer lipid vesicles that are released by cells and contain proteins, nucleic acids, and lipids. They can be internalized by other cells, inducing inflammatory responses and instigating toxicities in the recipient cells. Exosomes can also serve as therapeutic vehicles by transporting protective cargo to maintain homeostasis. Multiple studies have shown that exosomes can initiate and participate in the regulation of neuroinflammation, improve neurogenesis, and are closely related to the pathogenesis of central nervous system (CNS) diseases, including multiple sclerosis (MS). Exosomes can be secreted by both neurons and glial cells in the CNS, and their contents change with disease occurrence. Due to their ability to penetrate the blood-brain barrier and their stability in peripheral fluids, exosomes are attractive biomarkers of CNS diseases. In recent years, exosomes have emerged as potential therapeutic agents for CNS diseases, including MS. However, the molecular pathways in the pathogenesis of MS are still unknown, and further research is needed to fully understand the role of exosomes in the occurrence or improvement of MS disease. Thereby, in this review, we intend to provide a more complete understanding of the pathways in which exosomes are involved and affect the occurrence or improvement of MS disease.

Bifidobacterium breve Probiotic Compared to Lactobacillus casei Causes a Better Reduction in Demyelination and Oxidative Stress in Cuprizone-Induced Demyelination Model of Rat.

Despite the anatomical separation, strong evidence suggested a bidirectional association between gut microbiota and central nervous system. Cross-talk between gut microbiota and brain has an important role in the pathophysiology of neurodegenerative disorders and regenerative processes. However, choosing the appropriate probiotics and combination therapy of probiotics to provide a synergistic effect is very crucial. In the present study, we investigated the effect of Lactobacillus casei (L. casei) and Bifidobacterium breve (B. breve) on alternation performance, oxidant/antioxidant biomarkers, the extent of demyelination, and the expression level of HO-1, Nrf-2, Olig2, MBP, PDGFRα, and BDNF in cuprizone (CPZ)-induced demyelination model of rat corpus callosum. In order to induce this model, rats received oral administration of CPZ 0.6% w/w in corn oil for 28 days. Then, L. casei, B. breve, or their combinations were orally administrated for 28 days. Y maze test was performed to investigate the alternation performance. Oxidant/antioxidant biomarkers were determined by colorimetric methods. Extent of demyelination was investigated using FluoroMyelin staining. The genes' expression levels of antioxidant and myelin lineage cells were assessed by quantitative real time PCR. The results showed the probiotics supplementation significantly improve the alternation performance and antioxidant capacity in demyelinated corpus callosum. Interestingly, B. breve supplementation alleviated demyelination and oxidative stress levels more than the administration of L. casei alone or the combination of two probiotics. These observations suggest that B. breve could provide a supplementary strategy for the treatment of multiple sclerosis by increasing antioxidant capacity and remyelination.

Sub-acute administration of metal-organic Framework-5 induces behavioral impairments and augments the levels of oxidative stress and inflammation in the brain of rats.

Metal-organic frameworks (MOFs) are known as potential pharmaceutical carriers because of their structure. Here, we evaluated the sub-acute administrations of MOF-5 on behavioral parameters, oxidative stress, and inflammation levels in rats. Thirty-two male Wistar rats received four injections of saline or MOF-5 at different doses which were 1, 10, and 50 mg/kg via caudal vein. Y-Maze and Morris-Water Maze (MWM) tests were used to explore working memory and spatial learning and memory, respectively. The antioxidant capacity and oxidative stress level of brain samples were assessed by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) assay, respectively. The expression levels of GFAP, IL-1ß, and TNF-α were also measured by quantitative real-time reverse-transcription PCR (qRT-PCR). Sub-acute administration of MOF-5 reduced the spatial learning and memory as well as working memory, dose-dependently. The levels of FRAP were significantly reduced in rats treated with MOF-5 at higher doses. The Malondialdehyde (MDA) levels increased at the dose of 50 mg/kg. Additionally, the expression levels of IL-1ß and TNF-α were significantly elevated in the rats' brains that were treated with MOF-5. Our findings indicate that sub-acute administration of MOF-5 induces cognitive impairment dose-dependently which might be partly mediated by increasing oxidative stress and inflammation.

The Role of Intestinal Microbiota and Probiotics Supplementation in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a neurological autoimmune disorder predominantly afflicting young adults. The etiology of MS is intricate, involving a variety of environmental and genetic factors. Current research increasingly focuses on the substantial contribution of gut microbiota in MS pathogenesis. The commensal microbiota resident within the intestinal milieu assumes a central role within the intricate network recognized as the gut-brain axis (GBA), wielding beneficial impact in neurological and psychological facets. As a result, the modulation of gut microbiota is considered a pivotal aspect in the management of neural disorders, including MS. Recent investigations have unveiled the possibility of using probiotic supplements as a promising strategy for exerting a positive impact on the course of MS. This therapeutic approach operates through several mechanisms, including the reinforcement of gut epithelial integrity, augmentation of the host's resistance against pathogenic microorganisms, and facilitation of mucosal immunomodulatory processes. The present study comprehensively explains the gut microbiome's profound influence on the central nervous system (CNS). It underscores the pivotal role played by probiotics in forming the immune system and modulating neurotransmitter function. Furthermore, the investigation elucidates various instances of probiotic utilization in MS patients, shedding light on the potential therapeutic advantages afforded by this intervention.