Cytokines and Extracellular Matrix Remodeling in the Central Nervous System

Abstract

Abstract The extracellular space consists of approximately a quarter of the volume of the central nervous system (CNS), which is otherwise mostly occupied by cellular elements and blood vessels. This space is filled with various ions, transmitters, metabolites, peptides, and extracellular matrix (ECM) molecules produced by neurons and glia. The best-known ECM domain in brain was recently visualized as “interstitial clefts,” consisting of astrocytic processes enveloped by basal lamina with ECM molecules detected within the clefts. Both the basal lamina and the ECM serve as depots for cytokines and growth factors and both contain proteoglycans, important molecules with the capacity to bind cytokines and growth factors. The ECM components and their ability to store cytokines and growth factors are important in CNS cell development, such as stem cell cytogenesis, synaptic plasticity but also in CNS pathology. It is postulated that most stem cell niches are composed of ECM and other noncellular components that regulate stem cell control and allow for homologous cell–cell interactions as well as stem cell migration toward a damaged tissue. Thus, ECM serves as an immediate source of cytokines and growth factors during normal CNS development, as well as during CNS injury and inflammation. In addition, recent studies have shown that an enzymatic degradation of ECM components may result in uncontrolled diffusion of cytokines and growth factors as well as the activation of the ECM molecules, for example, laminin, therefore contributing to CNS pathology. The information contained in this chapter describes a number of ECM components in the CNS and their role in both normal physiological conditions and CNS injury. The interactions of cytokines and ECM molecules during CNS injury is presented using examples of CNS disease involving either autoimmune (multiple sclerosis), bacterial (meningitis), viral (HIV dementia), or neoplastic (glioma) pathogenic stimuli.