Neuropharmacology

Biography

Biography: Carola Forster

Abstract

The microenvironment of the central nervous system (CNS) is maintained by the blood brain barrier (BBB) which is made up of brain capillary endothelial cells. Injury or damage compromises BBB integrity. Traumatic brain injury (TBI) results from an outward impact that causes immediate mechanical disruption of brain tissue and delayed pathogenic events which collectively mediate widespread neurodegeneration. The initial impact is usually followed by the development of secondary injury as a result of cerebral ischemia which leads to brain swelling and edema, activation of inflammation and BBB leakage. Although several models for studying the mechanisms of TBI exist, no single system covers all the spectrum of events that might occur during TBI. Thus, in an attempt to include both the initial outward injury during TBI and the secondary injury as a result thereof in one model system, we established an in vitro TBI model using stretch in combination with oxygen-glucose deprivation (OGD). Using this model, the effects of ischemia and TBI to calcium levels and inflammatory response in the BBB through the brain microvascular endothelial cell cEND were investigated. Results show that damage to cEND cells leads to increased lactate dehydrogenase enzyme (LDH) and nitric oxide (NO) release into the cell. Moreover, mRNA expression of inflammatory markers interleukin (IL)-6, IL-1α, chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor (TNF)-α also increased. This inflammatory cascade triggers the opening of calcium ion channels demonstrated by increased calcium levels in cEND cells subjected to OGD and incubated with astrocyte-conditioned medium.