Chronic cerebral hypoperfusion and blood-brain barrier disruption in uninjured brain areas of rhesus monkeys subjected to transient ischemic stroke

Abstract

Blood-brain barrier (BBB) disruption is a pivotal pathophysiological process in ischemic stroke. Although temporal changes in BBB permeability during the acute phase have been widely studied, little is known about the chronic phase of cerebrovascular changes that may have a large impact on the long-term outcome. Therefore, this study was aimed to measure cerebral vascular abnormalities using CT perfusion in nine rhesus monkeys subjected to transient middle cerebral artery occlusion (tMCAO) for ≥1 year (MCAO-1Y+). The level of cerebral perfusion demonstrated by mean transit time was significantly higher in the ipsilateral caudate nucleus, white matter, thalamus, hippocampus, and contralateral thalamus in MCAO-1Y+ compared with the other nine age-matched control monkeys. The increase in BBB permeability measured through the permeability surface was found in the same ten regions of interest ipsilaterally and contralaterally. We also found decreased levels of Aβ 42/40 ratio in the cerebrospinal fluid (CSF), suggesting a potential link between post-MCAO cognitive decline and Aβ metabolism. Overall, we demonstrated significant cerebral hypoperfusion, BBB disruption, and CSF Aβ decrease during the rehabilitation stage of ischemic stroke in a non-human primate model. Future studies are needed to elucidate the cause-effect relationship between cerebrovascular disruptions and long-term neurological deficits.