The Chronic Vascular and Haemodynamic Response after Permanent Bilateral Common Carotid Occlusion in Newborn and Adult Rats

Abstract

Vascular growth and redistribution of flow can compensate for arterial occlusion and possibly reduce the effects of hypoperfusion. As yet there is limited information on the age-dependent nature of vasculature remodelling. In this study, we have monitored the vascular and morphologic changes using magnetic resonance imaging and histology in a chronic bilateral common carotid artery occlusion (BCCAO) model in both newborn and adult rats. Acutely, cerebral blood flow (CBF) decreased immediately after BCCAO, producing a state of oligemic hypoperfusion. At 6 months after BCCAO in both adult and neonatal rats, the CBF had normalised at control values. To investigate the underlying mechanism for the return of CBF to control values, intra- and extracerebral magnetic resonance angiograms (MRAs) were acquired. As expected, signal from the common carotid arteries was present in the sham-operated rats, but was absent in the BCCAO animals. India ink angiograms demonstrated more tortuous basilar arteries in the adult rats post-BCCAO and MRAs demonstrated more extracerebral midline collaterals in the neonatal rats post-BCCAO, indicating different modes of vascular adaptation dependent on the age at onset of the insult. Both groups had collateral vessels arising from the vertebral arteries, and BCCAO was also associated with increased diameter of basilar, posterior cerebral, posterior communicating, internal carotid, middle cerebral and anterior cerebral arteries. Our study suggests that the developing and mature animals exhibit different patterns of vascular remodelling and that the BCCAO hypoperfusion model will be useful for investigating age-dependent vascular events in response to vaso-occlusive disease.