THE INFLUENCE OF PLASMA-PROTEINS ON THE DISTRIBUTION OF LEUKOCYTES WITHIN THE BRAIN PARENCHYMA IN A MURINE MODEL OF STROKE

Inflammatory responses are thought to play an important role in the ex acerbation of neuronal loss following stroke. Leucocyte recruitment fo llowing cerebral ischaemia has been demonstrated in experimental anima ls, and procedures which reduce the entry of leucocytes into the brain reduce neuronal loss and improve aspects of functional recovery in th ese models. In this study we investigate whether leakage of plasma pro teins into the central nervous system (CNS) following ischaemia influe nces leucocyte adhesion within the parenchyma. Using an in vitro adhes ion assay, we demonstrate that the addition of exogenous serum protein s increases macrophage adhesion to CNS tissue, Following permanent mid dle cerebral artery occlusion (MCAO) in mice, plasma proteins leak int o the apparently healthy cortex surrounding the infarcted area. We sho w that there is increased macrophage adhesion to sections in the borde r region where endogenous plasma proteins are present within the paren chyma, Using immunohistochemistry, we co-localize plasma protein distr ibution within the tissue with leucocyte recruitment following MCAO, W e show that monocytes, not neutrophils, infiltrate the lesion border w here plasma proteins are present in the parenchyma, This distribution is compatible with their contributing to neuropathology, whereas neutr ophils are found in clusters in the lesion core, We conclude that leak age of plasma proteins into the brain could influence leucocyte adhesi on within the parenchyma, Recruited monocytes may exacerbate neuropath ology in situations such as permanent cerebral ischaemia, where disrup tion of the blood-brain barrier occurs.