Caspase-3 dependent, induction of barrier dysfunction and hyperpermeability in blood-brain barrier endothelial cells.

Authors

Himakarnika Alluri, Rickesha L Wilson, Morgan Merriman, Chinchusha Anasooya Shaji, Chen Chen, Gabriela Seplovich, Devendra A Sawant, Chander Peddaboina, Jason H Huang, Binu Tharakan

Published in

Brain injury. Pages 1-9. Sep 18, 2026. Epub Sep 18, 2026.

Abstract

Blood-brain barrier (BBB) dysfunction and associated microvascular hyperpermeability lead to brain edema and elevation of intracranial pressure in traumatic and ischemic brain injuries. Pro-inflammatory cytokines, interleukin (IL-1β) and tumor necrosis factor (TNF-α), are up-regulated in such conditions and serve as endogenous activators of caspase-3 and apoptosis. The objective of this study was to comparatively test how these cytokines regulate caspase-3-mediated BBB breakdown/hyperpermeability, and understand if these effects were cell death dependent.
Rat brain microvascular endothelial cells were exposed to IL-1β, TNF-α, or caspase-3 activator, staurosporine (STS). Blood-brain barrier integrity and functions were determined by monolayer permeability, tight junction integrity, and cytoskeletal integrity. The changes in mitochondrial reactive oxygen species (ROS) and caspase-3 activity were evaluated microscopically and fluorometrically, respectively.
IL-1β, TNF-α, and STS induced caspase-3 activation, tight junction/cytoskeletal disorganization, and monolayer hyperpermeability. These effects were inhibited by a caspase-3 inhibitor, Z-DEVD-fmk. Treatments had no effect on ROS formation.
This comparative study shows that, in BBB endothelial cells, IL-1β, TNF-α, and STS induce tight junction/cytoskeletal disorganization and hyperpermeability via Caspase-3 mediated breakdown of the tight junction proteins. Effects are independent of ROS formation, one of the significant factors that promote blood-brain barrier dysfunctions in neurological disorders.

PMID:
42757768
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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