Synaptic Plasticity and Neuroinflammation: A Therapeutic Approach to Neurological Illnesses

Abstract

The central nervous system (CNS) has historically been viewed as an immune-privileged site, shielded from conventional immune responses. However, recent discoveries have challenged this notion, revealing intricate bidirectional communication between the nervous and immune systems. Evidence indicates that the CNS actively participates in immune surveillance, and immune mediators profoundly influence synaptic remodeling and plasticity -processes crucial for learning, memory, and cognition. This chapter explores the emerging role of glial cells as active participants in CNS immune responses and synaptic modulation, rather than mere support cells. It highlights the significant impact of immunological factors like cytokines and major histocompatibility complex molecules on synaptic memory processes-an influence long underestimated. Furthermore, the chapter examines the potential implications of this neuroimmune crosstalk in the pathophysiology of neuroinflammatory disorders associated with cognitive decline, such as Parkinson’s disease and Alzheimer’s disease. The interplay between abnormal inflammatory substance expression during CNS inflammation and disease-specific defects may disrupt synaptic adaptation and remodeling, destabilizing neuronal networks and contributing to cognitive impairment. Challenging the traditional immune-privileged view of the CNS, this chapter provides insights into the complex mechanisms underlying neurological disorders and fosters a deeper understanding of nervous-immune system communication. Ultimately, this emerging knowledge holds promise for developing novel therapeutic strategies targeting the neuroimmune interface to treat cognitive and neurodegenerative diseases. © 2025 selection and editorial matter, Sangeeta Singh, Sachchida Nand Rai, and Santosh Kumar Singh.