Reduction of functional capillary density in human brain after stroke

Area of Science:

• Neuroscience
• Cerebrovascular Physiology
• Medical Imaging

Background:

• Brain tissue blood flow often normalizes post-ischemia, exhibiting "luxury" hyperemia with low metabolism.
• The relationship between this hyperemia and capillary density (high, normal, or low) remains unclear.
• Understanding this link may reveal if functional capillary density varies and its coupling to blood flow or metabolism.

Purpose of the Study:

• To investigate the extent of functional capillary density in post-ischemic brain tissue.
• To determine if functional capillary density is coupled to blood flow or metabolism.
• To define functional capillaries as those transporting glucose.

Main Methods:

• Positron emission tomography (PET) used to obtain in vivo hemodynamic variables in five stroke patients.
• Functional capillary density (Dcap) and capillary transit time (tcap) calculated from hemodynamic data.
• Patients studied twice: within 36 hours and 1 week post-ischemia, comparing "ischemic" regions to contralateral hemispheres.

Main Results:

• "Ischemic" regions showed proportionately low metabolism and functional capillary density compared to normal values.
• A reduction in functional exchange vessel density was observed as early as 36 hours post-insult.
• In "ischemic" regions, oxygen extraction was inversely related to capillary transit time, limited by low capillary density.
• Reduced capillary density persisted despite adequate tissue perfusion returning later.

Conclusions:

• Functional capillary density is reduced in post-ischemic brain tissue.
• The persistent reduction in capillary density is associated with altered tissue metabolism, not solely blood flow.
• Capillary density changes appear to be coupled to metabolic demand rather than perfusion levels in the post-ischemic state.