Review: cerebral microvascular pathology in ageing and neurodegeneration

Abstract

This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase. This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in ageing, Alzheimer's disease and leukoaraiosis, and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in leukoaraiosis, and cerebral blood flow is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in Alzheimer's disease, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation.

© 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

Figures

Fig. 1

Schematic of the cerebral blood supply. (Reprinted from [17]).

Fig. 2

Tortuous arterioles in the white matter. (A) This thick celloidin section stained with collagen IV shows two tortuous arterioles in cavities. (B) This thick celloidin section stained with AP shows several arterioles with tortuosity beginning as they enter the white matter. (Reprinted from [20]).

Fig. 3

Severe periventricular venous collagenosis in the brain of a subject with leukoaraiosis. (A) This thin paraffin section stained with trichrome shows numerous affected veins (green) near the lateral ventricle. (B) This thin paraffin section stained with &E shows veins with collagenosis (arrows) at higher magnification. (Reprinted from [20]).

Fig. 4

String vessels (arrows) in a thick celloidin section stained with antibody to collagen IV.

Fig. 5

Graph of vascular density in normal, AD, LA, and brain irradiation.

Fig. 6

Amyloid β deposited in and around capillaries (arrows) larger blood vessels. Thick celloidin section stained with antibodies to collagen IV and Aβ. (Reprinted from [189]).

Fig. 7

Schematic of capillary loss and string vessel formation. (Reprinted from [44]).

Fig. 8

Lipid microemboli in brain capillaries in a patient one day after cardiac surgery assisted by CPB. (Reprinted from [190]).

Fig. 9

A lipid embolus (large arrow) in a brain capillary in a patient 17 days after cardiac surgery assisted by CPB. Note the loss of AP staining and apparent degenerative changes in the capillary down stream from the embolus. (Reprinted from [167]).

Fig. 10

A lipid embolus (large arrow) showing birefringence in a photograph with a polarizing filter. Note the loss of AP staining and apparent degenerative changes in the capillary down stream from the embolus. (Reprinted from [167]).