Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair

Hila Israelov (1) , Orly Ravid (1) , Dana Atrakchi (1) , Daniel Rand (1) , Shirin Elhaik (1) , Yael Bresler (1) , Rachel Twitto-Greenberg (1) , Liora Omesi (1) , Sigal Liraz-Zaltsman (1) , Fabien Gosselet (2) , Michal Schnaider Beeri (1) , Itzik Cooper (1)

1 Chaim Sheba Medical Center
2 LBHE - Laboratoire de la Barrière Hémato-Encéphalique

Excessive inflammation might activate and injure the blood-brain barrier (BBB), a common feature of many central nervous system (CNS) disorders. We previously developed an in vitro BBB injury model in which the organophosphate paraoxon (PX) affects the BBB endothelium by attenuating junctional protein expression leading to weakened barrier integrity. The objective of this study was to investigate the inflammatory cellular response at the BBB to elucidate critical pathways that might lead to effective treatment in CNS pathologies in which the BBB is compromised. We hypothesized that caspase-1, a core component of the inflammasome complex, might have important role in BBB function since accumulating evidence indicates its involvement in brain inflammation and pathophysiology.

Mots clés: Caspase-1; Inflammasome; Blood-brain barrier; Paraoxon; Permeability; Adhesion; Transmigration; Inflammation

Domaines: Sciences du Vivant [q-bio]

Hila Israelov, Orly Ravid, Dana Atrakchi, Daniel Rand, Shirin Elhaik, et al.. Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair. Journal of Neuroinflammation, 2020, 17 (1), ⟨10.1186/s12974-020-01927-w⟩. ⟨hal-03126925⟩