Morphometric analysis of CNS microvascular endothelium

Area of Science:

• Neuroscience
• Vascular Biology
• Cell Biology

Background:

• The blood-brain barrier (b-bb) protects the brain from circulating substances.
• Its unique ultrastructure is crucial for selective permeability.
• Previous studies suggested increased metabolic capacity and pericyte involvement in b-bb function.

Purpose of the Study:

• To quantify and compare ultrastructural features of blood-brain barrier (b-bb) capillaries with non-barrier capillaries.
• To investigate the role of pinocytotic vesicles, interendothelial junctions, wall thickness, and pericytes in b-bb function.
• To challenge existing hypotheses regarding the metabolic demands and pericyte function at the b-bb.

Main Methods:

• Quantitative image analysis of mouse cerebral capillaries (gray and white matter), area postrema capillaries, and muscle capillaries.
• Utilized a digitized bit pad and microcomputer system for rapid analysis.
• Focused on pinocytotic vesicle density, interendothelial junctional complexes, wall thickness, mitochondrial density, and pericyte coverage.

Main Results:

• Blood-brain barrier (b-bb) capillaries exhibited significantly fewer pinocytotic vesicles compared to area postrema and muscle capillaries.
• Interendothelial junctions in non-barrier capillaries showed separations, absent in normal b-bb capillaries.
• Barrier capillaries were 39% thinner than non-barrier capillaries.
• No significant differences in mitochondrial density or pericyte area were observed across all capillary types.

Conclusions:

• The blood-brain barrier (b-bb) possesses distinct ultrastructural features, including reduced vesicular transport and continuous tight junctions, contributing to its barrier function.
• The observed differences challenge the notion of universally increased metabolic capacity in barrier capillaries.
• Pericytes do not appear to play a significant role in the normal functioning of the blood-brain barrier (b-bb).