An In Vitro Model of Ischemic Stroke

Brain stroke is a devastating cerebrovascular disease and ranks as the third most common cause of death and disability in the US. Altered blood–brain barrier (BBB) signaling and permeability characteristics during stroke can increase the risk for life-threatening hemorrhagic transformation or damaging brain edema. The BBB plays a crucial role in maintaining the permeability and CNS homeostasis under physiological/pathological conditions by protecting the brain from the fluctuations in plasma constituents. Many in vitro brain endothelial cell culture models have been developed and studied over the past several decades to understand the pathophysiological mechanisms and role of the BBB in stroke. Restrictive barrier properties of brain endothelial cells have been shown to be predominantly influenced by astrocytes and astrocyte-secreting factors using coculture systems. By using astrocyte-endothelial cocultures, it is possible to model in vivo BBB characteristics, while allowing for mechanistic studies to be performed. Hence, the application of in vitro astrocyte-endothelial coculture BBB systems is a powerful technique to understand and investigate the pathophysiological mechanisms in stroke. This approach can be utilized to uncover cell signaling pathways and that may identify new neurovascular drug targets to treat this devastating brain vascular disease.