Platelet-Derived PDGF-A Disrupts Blood-Brain Barrier Integrity in Ischemic Stroke-Brief Report

Area of Science:

• Neuroscience
• Vascular Biology
• Hematology

Background:

• Ischemic stroke (IS) is a leading cause of death and disability globally.
• Cerebral ischemia disrupts the blood-brain barrier (BBB), increasing permeability and worsening stroke outcomes.
• Platelets play complex roles in IS, contributing to both vascular integrity and infarct progression.

Purpose of the Study:

• To investigate the role of platelet activation in blood-brain barrier breakdown during ischemic stroke.
• To identify specific platelet-derived factors responsible for endothelial dysfunction and vascular leakage.

Main Methods:

• Ischemic stroke was induced in mice using transient middle cerebral artery occlusion.
• Vascular leakage was assessed using intravital 2-photon microscopy, Western blotting, and immunohistochemistry.
• Brain microvascular endothelial cell barrier integrity was measured by transendothelial electrical resistance.

Main Results:

• Ischemic stroke caused time-dependent albumin leakage into the brain parenchyma, indicating BBB breakdown.
• Platelet activation released platelet-derived growth factor (PDGF)-A, which compromised endothelial cell layer integrity and vascular integrity in vivo.
• Absence of α-granule content or PDGF blockade prevented endothelial disruption and vascular leakage.

Conclusions:

• Platelet-derived PDGF-A directly impairs blood-brain barrier integrity, leading to detrimental vascular leakage.
• These findings elucidate a key mechanism of thromboinflammation in ischemic stroke.
• Targeting PDGF-A may offer a therapeutic strategy to mitigate BBB damage in IS.