Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following...

Area of Science:

• Neuroscience
• Vascular Biology
• Stroke Research

Background:

• Normal brain function relies on vascular supply matching metabolic demand.
• Impaired neurovascular coupling, or the inability to increase blood flow to active brain regions, can lead to poor outcomes after stroke, even with successful blood vessel recanalization (futile recanalization).

Purpose of the Study:

• To investigate the role of capillary pericytes and blood flow dynamics in impaired neurovascular coupling after stroke.
• To explore the mechanisms underlying futile recanalization.

Main Methods:

• Mice underwent induced anterior middle cerebral artery occlusion using photothrombosis.
• Cerebral perfusion and neurovascular coupling were assessed using optical coherence tomography and laser speckle contrast imaging.
• Capillary pericyte contraction and capillary blood flow stalling were quantified in peri-ischemic tissue.

Main Results:

• Arterial occlusion caused significant capillary blood flow reduction and capillary pericyte contraction in the peri-ischemic cortex.
• Remaining perfused capillaries exhibited increased flow stalling.
• Neurovascular coupling responses to whisker stimulation were reduced in the peri-ischemic sensory cortex.

Conclusions:

• Stroke-induced arterial occlusion leads to capillary pericyte contraction and flow stalling.
• This capillary dysfunction is associated with neurovascular uncoupling.
• Impaired neurovascular coupling due to capillary dysfunction may be a key mechanism contributing to futile recanalization, highlighting a potential therapeutic target.