Ricerc@Sapienza

Matrix metalloproteinases (MMPs) are a large family of ubiquitous extracellular endopeptidases, which play important roles in a variety of physiological and pathological conditions, from the embryonic stages throughout adult life. Their extraordinary physiological “success” is due to concomitant broad substrate specificities and strict regulation of their expression, activation and inhibition levels. In recent years, MMPs have gained increasing attention as significant effectors in various aspects of central nervous system (CNS) physiology.

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM).

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy.