The influence of plasma proteins on the distribution of leucocytes within the brain parenchyma in a murine model of stroke.

Abstract

Inflammatory responses are thought to play an important role in the exacerbation of neuronal loss following stroke. Leucocyte recruitment following cerebral ischaemia has been demonstrated in experimental animals, and procedures which reduce the entry of leucocytes into the brain reduce neuronal loss and improve aspects of functional recovery in these models. In this study we investigate whether leakage of plasma proteins into the central nervous system (CNS) following ischaemia influences leucocyte adhesion within the parenchyma. Using an in vitro adhesion assay, we demonstrate that the addition of exogenous serum proteins increases macrophage adhesion to CNS tissue. Following permanent middle cerebral artery occlusion (MCAO) in mice, plasma proteins leak into the apparently healthy cortex surrounding the infarcted area. We show that there is increased macrophage adhesion to sections in the border region where endogenous plasma proteins are present within the parenchyma. Using immunohistochemistry, we co-localize plasma protein distribution within the tissue with leucocyte recruitment following MCAO. We show that monocytes, not neutrophils, infiltrate the lesion border where plasma proteins are present in the parenchyma. This distribution is compatible with their contributing to neuropathology, whereas neutrophils are found in clusters in the lesion core. We conclude that leakage of plasma proteins into the brain could influence leucocyte adhesion within the parenchyma. Recruited monocytes may exacerbate neuropathology in situations such as permanent cerebral ischaemia, where disruption of the blood-brain barrier occurs.