Chronic pathological conditions often induce persistent systemic inflammation, contributing to neuroinflammatory diseases like Multiple Sclerosis (MS). MS is known for its autoimmune-mediated damage to myelin, axonal injury, and neuronal loss which drive disability accumulation and disease progression, often manifesting as cognitive impairments. Understanding the involvement of neural stem cells (NSCs) and neural progenitor cells (NPCs) in the remediation of MS through adult neurogenesis (ANG) and gliogenesis—the generation of new neurons and glial cells, respectively is of great importance. Hence, these phenomena, respectively, termed ANG and gliogenesis, involve significant structural and functional changes in neural networks. Thus, the proper integration of these newly generated cells into existing circuits is not only key to understanding the CNS’s development but also its remodeling in adulthood and recovery from diseases such as MS. Understanding how MS influences the fate of NSCs/NPCs and their possible neuroprotective role, provides insights into potential therapeutic interventions to alleviate the impact of MS on cognitive function and disease progression. This review explores MS, its pathogenesis, clinical manifestations, and its association with ANG and gliogenesis. It highlights the impact of altered NSCs and NPCs’ fate during MS and delves into the potential benefits of its modifications. It also evaluates treatment regimens that influence the fate of NSCS/NPCs to counteract the pathology subsequently.

Transient receptor potential vanilloid 4 (TRPV4) is a polymodal cation channel that is widely expressed in sensory neurons, immune cells, and structural tissues, where it integrates mechanical, osmotic, and chemical stimuli to regulate both physiological responses and disease-associated signaling. Mast cells (MCs), key immune effector cells capable of rapid mediator release through degranulation, also express TRPV4. Increasing evidence supports TRPV4-MC signaling as an important neuroimmune interface, linking mechanical and inflammatory stimuli to tissue hypersensitivity and pain. In this review, we synthesize current evidence supporting a role for TRPV4 in MC-associated neuroimmune signaling across multiple disease contexts while distinguishing settings in which TRPV4 directly regulates MC activation from those in which MC responses arise through multicellular tissue interactions. Direct TRPV4-dependent MC activation has been described in conditions such as LL-37–driven rosacea and mechanically induced inflammation, whereas in disorders including asthma, visceral hypersensitivity, bladder pain syndromes, and osteoarthritis, TRPV4 activity in epithelial, neuronal, or stromal compartments more often influences MC function indirectly through ATP–purinergic signaling, cytokine release, and neuropeptide-mediated crosstalk. Across systems, TRPV4 emerges not as a single pathogenic switch but as part of a context-dependent signaling network whose functional consequences depend on cell type, tissue microenvironment, and disease stage. Altogether, these findings identify TRPV4 as a therapeutically actionable node within neuroimmune signaling pathways and support the development of tissue-specific and combination strategies targeting both TRPV4 activity and MC-mediated signaling in chronic inflammatory and pain disorders.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats’ model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats’ model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA.