Studying Human Brain Inflammation in Leptomeningeal and Choroid Plexus Explant Cultures.

Abstract

The meninges (dura, pia and arachnoid) are critical membranes encasing and protecting the brain within the skull. The leptomeninges, which comprise the arachnoid and pia, have many functions beyond brain protection including roles in neurogenesis, fibrotic scar formation and brain inflammation. Similarly, the choroid plexus plays important roles in normal brain function but is also involved in brain inflammation. We have begun studying the role of human leptomeninges and choroid plexus in brain inflammation and leptomeninges in fibrotic scar formation, using human brain derived explant cultures. To study the composition of the cells generated in these explants we undertook immunocytochemical characterisation. Cells, mainly pericytes and meningeal macrophages, emerge from leptomeningeal explants (LME's) and respond to inflammatory mediators by producing inflammatory molecules. LME-derived cells also respond to mechanical injury and cytokines, providing an in vitro human brain model of fibrotic scar formation. Choroid plexus explants (CPE's) generate epithelial cells, pericytes and microglia/macrophages. CPE-derived cells also respond to inflammatory mediators. LME and CPE explants survive and generate cells for many months in vitro and provide a remarkable opportunity to study basic mechanisms of human brain inflammation and fibrosis and to test human-active anti-inflammatory and anti-scarring treatments.