Related Experiment Video
Updated: Jun 4, 2026

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction
Published on: January 12, 2016
Caspase-3 contributes to ZO-1 and Cl-5 tight-junction disruption in rapid anoxic neurovascular unit damage
Christoph M Zehendner1, Laura Librizzi, Marco de Curtis
1Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
Background:
Tight-junction (TJ) protein degradation is a decisive step in hypoxic blood-brain barrier (BBB) breakdown in stroke. In this study we elucidated the impact of acute cerebral ischemia on TJ protein arrangement and the role of the apoptotic effector protease caspase-3 in this context.
Methodology/Principal Findings:
We used an in vitro model of the neurovascular unit and the guinea pig whole brain preparation to analyze with immunohistochemical methods the BBB properties and neurovascular integrity. In both methodological approaches we observed rapid TJ protein disruptions after 30 min of oxygen and glucose deprivation or middle cerebral artery occlusion, which were accompanied by strong caspase-3 activation in brain endothelial cells (BEC). Surprisingly only few DNA-fragmentations were detected with TUNEL stainings in BEC. Z-DEVD-fmk, an irreversible caspase-3 inhibitor, partly blocked TJ disruptions and was protective on trans-endothelial electrical resistance.
Conclusions/Significance:
Our data provide evidence that caspase-3 is rapidly activated during acute cerebral ischemia predominantly without triggering DNA-fragmentation in BEC. Further we detected fast TJ protein disruptions which could be partly blocked by caspase-3 inhibition with Z-DEVD-fmk. We suggest that the basis for clinically relevant BBB breakdown in form of TJ disruptions is initiated within minutes during ischemia and that caspase-3 contributes to this process.
More Related Videos
10:45Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization
Published on: January 13, 2012
08:56Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction
Published on: May 7, 2015
Related Concept Videos
Caspases
Cellular Injury IV: Necrosis
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Cell Motility through Blebbing
Blebbing Through the Matrix
In multicellular...