ABSTRACT
Cerebral blood vessels are damaged in a wide variety of neurological illnesses. When permeability of the blood vessels is altered, substances normally excluded from the brain are allowed to enter, causing brain edema. Severe disruption of the vasculature leads to hemorrhage. Both edema and hemorrhage are life threatening. Proteases and free radicals participate in the final common pathway that leads to blood vessel breakdown. Neutral proteases, such as the matrix metalloproteinases (MMPs) and the plasminogen/plasmin system interact with free radicals to cause damage to endothelial cells and the extracellular matrix and other cells surrounding the vessels. For the past several years our laboratory has been studying the MMPs, which are a gene family of neutral proteases that degrade all components of the extracellular
matrix. They have been shown by other laboratories and by us to be important in normal development, wound healing, and pathological processes. An important role is to modulate blood-brain barrier (BBB) function during neuro-inflammation. The MMPs can be both produced endogenously by most brain cells and delivered to the brain packaged in leukocytes. They alter BBB permeability by attacking the extracellular matrix around blood vessels.
