Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury.

Area of Science:

• Neuroscience
• Vascular Biology
• Traumatic Brain Injury Research

Background:

• Traumatic brain injury (TBI) is common, but predictors of poor long-term outcomes, including cardiovascular disease and neurodegeneration, remain unclear.
• Identifying factors that exacerbate TBI's effects is crucial for improving patient prognoses.

Purpose of the Study:

• To test if preexisting cerebrovascular impairment worsens metabolic and vascular dysfunction after TBI.
• To investigate the impact of combined bilateral carotid artery stenosis (BCAS) and TBI on cerebrovascular health and gene expression.

Main Methods:

• Male mice underwent BCAS to reduce cerebral blood flow, followed by TBI or sham surgery 30 days later.
• Assessed gene expression (single nuclei RNA sequencing), cerebral blood flow, metabolic function, oxidative damage, vascular health, and angiogenesis.

Main Results:

• Combined BCAS and TBI altered endothelial cell gene expression profiles more than either challenge alone.
• BCAS induced vascular oxidative damage, inflammation, reduced vascular density, and decreased angiogenic cells.
• Both BCAS and TBI impaired cerebrovascular responses, and combined insults increased intravascular protein accumulation.

Conclusions:

• Preexisting vascular impairment significantly alters cerebrovascular health and function.
• The combination of vascular impairment and TBI may lead to exacerbated negative outcomes and complications.