Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice

Area of Science:

• Neurology
• Neuroscience
• Vascular Biology

Background:

• Vascular cognitive impairment (VCI) is a major cause of dementia, but lacks adequate animal models for studying human neuropathology.
• Current research faces challenges in replicating the complex changes seen in human VCI within animal subjects.

Purpose of the Study:

• To develop and compare three distinct mouse models of chronic vascular diseases to better understand VCI development.
• To establish a more suitable animal model that accurately mimics human VCI.

Main Methods:

• Adult male C57/BL6 mice underwent three surgical procedures: transient bilateral common carotid artery occlusion (tBCCAO), bilateral common carotid artery stenosis (BCAS), or unilateral carotid artery occlusion.
• Cerebral blood flow (CBF) and spatial cognitive function were assessed up to four weeks post-operation.

Main Results:

• All models demonstrated varying degrees of CBF reduction and spatial memory impairment compared to controls.
• tBCCAO caused acute memory impairment, while unilateral occlusion resulted in milder, yet significant, memory deficits.
• A 30% reduction in bilateral or unilateral CBF induced significant memory disturbances, unlike a 20% reduction.

Conclusions:

• Bilateral common carotid artery stenosis (BCAS) using microcoils is identified as a viable alternative mouse model for VCI research.
• This BCAS model offers potential for studying VCI mechanisms and developing therapeutic interventions.