Total-body Irradiation Reduces Cerebrovascular Reactivity in Rhesus Macaques (Macaca mulatta).

Area of Science:

• Neuroscience
• Radiology
• Vascular Biology

Background:

• Radiation-induced brain injury (RIBI) is a progressive condition characterized by vascular damage, leading to cognitive decline.
• Early detection of RIBI is crucial for intervention, and Magnetic Resonance Imaging (MRI) offers a non-invasive method to assess vascular changes.
• Cerebrovascular reactivity (CVR) is a key indicator of brain vascular health.

Purpose of the Study:

• To evaluate the impact of total-body irradiation (TBI) and partial-body irradiation (PBI) on cerebral blood flow (CBF) and CVR in non-human primates.
• To assess the relationship between age, irradiation, and vascular changes in the brain.
• To investigate radiation-induced alterations in microvessel density.

Main Methods:

• Pseudo-continuous arterial spin labeling (pCASL) MRI was used to measure CBF and CVR in 123 rhesus macaques.
• Animals received varying doses of TBI or PBI, with age-matched controls.
• GLUT-1 staining was used to evaluate microvessel density in brain tissue.

Main Results:

• Irradiation significantly impaired CVR in male macaques (7-12 years old).
• In control animals, CVR declined with age, but this age-related decline was absent in irradiated animals.
• Neither age nor irradiation significantly affected CBF, and no differences in microvessel density were observed.

Conclusions:

• Cerebrovascular reactivity (CVR) decreases with age in macaques, suggesting age-related vascular changes contribute to neurodegeneration.
• Total-body irradiation (TBI) impairs CVR in male macaques, indicating its utility in detecting radiation-induced vascular injury.
• Measuring CVR may allow for early intervention to mitigate radiation-induced brain injury (RIBI).