Pronounced arterial collateralization was induced after permanent rat cerebral four-vessel occlusion. Relation to neuropathology and capillary ultrastructure

The present study investigates chronic changes in cerebral arterial vessel system, microvasculature, and brain histopathology using an adult rat model based on permanent and stepwise occlusion of four cerebral vessels. Digital subtraction angiography (DSA) was performed to study chronic changes in arterial cerebral vessel system after permanent vessel occlusion. Long-lasting functional changes such as NMDA-, AMPA- and GABA(A)-receptor binding were detected in hippocampus and dentate gyrus using autoradiography. Structural changes in cerebral capillaries were investigated using light- and electron microscopy. Chronic cerebral oligemia did not cause any significant changes in the densities of excitatory glutamate and inhibitory GABA(A) receptors. By electron microscopy we could document, however, that most capillaries in vessel-occluded animals shrank, the endothelial cells were prominent with enlarged nuclei and increased cytoplasm, and the basal membrane was thickened. In contrast to the degenerative changes in brain capillaries, pronounced arterial collateralization was disclosed by DSA after chronic brain vessel occlusion. The model of chronic occlusion of four cerebral vessels is characterized by capillary degeneration and arterial collateralization proceeding in parallel. Thus, this rat model may be useful in investigations of long-lasting compensatory mechanisms contributing to cerebrovascular or neurodegenerative disorders.