Related Experiment Video
Updated: Jun 17, 2026
11:32
Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
Published on: January 3, 2025
The Caspase-1/GSDMD/PXN/VCAM-1 Cascade Mediates Cerebral Ischemia-Reperfusion Injury
Tongshuai Zhang1,2, Siyu Han1,2, Yao Zhang1,2
1Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China.
Summary
Pyroptosis in brain endothelial cells drives inflammation after stroke. Targeting this cell death pathway may offer new treatments for ischemic brain injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Pyroptosis, an inflammatory cell death, contributes to inflammatory diseases.
- Stroke is a leading cause of death, and its mechanisms in brain microvascular endothelial cells (BMECs) are unclear.
Purpose of the Study:
- Investigate pyroptosis in BMECs during cerebral ischemia-reperfusion (I/R).
- Elucidate the role of pyroptosis in exacerbating neuroinflammation and brain injury.
Main Methods:
- Studied pyroptosis levels in BMECs under I/R conditions.
- Analyzed caspase-1, GSDMD, VCAM-1, and phosphorylated PXN (p-PXN) pathways.
- Utilized omics analysis to identify molecular mechanisms.
Main Results:
- Pyroptosis is elevated in BMECs during I/R, correlating with macrophage infiltration and brain injury.
- Caspase-1 mediates GSDMD-dependent VCAM-1 expression, enhancing endothelial cell-macrophage adhesion.
- p-PXN amplifies VCAM-1-mediated adhesion, worsening cerebral ischemic injury.
Conclusions:
- Pyroptosis in non-glial, non-neuronal cells significantly contributes to neuroinflammation in ischemic stroke.
- The caspase-1/GSDMD/VCAM-1/p-PXN axis is a key pathway in this process.
- Targeting pyroptosis in BMECs presents a potential therapeutic strategy for ischemic brain injury.
Related Concept Videos
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:15Ischemic Stroke ll: Pathophysiology
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...