Whole brain irradiation-induced endothelial dysfunction in the mouse brain.

Area of Science:

• Neuroscience
• Oncology
• Vascular Biology

Background:

• Whole brain irradiation (WBI) is a standard treatment for brain metastases but can cause neurocognitive decline.
• Cellular senescence and cerebrovascular injury are implicated mechanisms behind WBI's adverse effects.
• Endothelial cells within the neurovascular unit are key targets of WBI-induced damage.

Purpose of the Study:

• To test if WBI-induced endothelial injury promotes endothelial dysfunction resembling an aging phenotype.
• To investigate the impact of WBI on cerebrovascular endothelial function in a preclinical model.

Main Methods:

• Young mice underwent a clinically relevant fractionated WBI protocol.
• Cranial windows were used to assess microvascular endothelial function.
• Laser Doppler flowmetry measured cerebral blood flow (CBF) responses to acetylcholine and ATP.

Main Results:

• WBI significantly diminished acetylcholine- and ATP-induced increases in regional CBF.
• These findings demonstrate impaired endothelium-dependent, NO-mediated responses post-WBI.
• Endothelial dysfunction in WBI-treated mice mimicked an accelerated aging phenotype.

Conclusions:

• WBI induces cerebrovascular endothelial dysfunction, contributing to long-term cognitive impairment.
• This endothelial dysfunction resembles accelerated aging of the cerebrovasculature.
• Maintaining cerebrovascular health is crucial for preserving cognitive function after WBI.