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.

Whole‐transcriptome sequencing identifies neuroinflammation, metabolism and blood–brain barrier related processes in the hippocampus of aged mice during perioperative period

“…Fluid flow also plays roles in BBB regulation and endothelial glycocalyx‐related gene expressions 62 . Platelet‐derived growth factor B is critical for pericyte coverage and BBB function, 63 while cerebral hypoperfusion, BBB disruption and CSF Aβ decrease are related to long‐term neurological deficits 64 . Just as modulation networks hint, POCD is caused by joint action of multiple CNS cell types under surgical stress.…”

“…62 Platelet-derived growth factor B is critical for pericyte coverage and BBB function, 63 while cerebral hypoperfusion, BBB disruption and CSF Aβ decrease are related to long-term neurological deficits. 64 Just as modulation networks hint, POCD is caused by joint action of multiple CNS cell types under surgical stress. The symptoms of POCD include impairments of memory, attention, action and perception, and several DEGs found in the present study (Ncam1, Srf, etc.)…”

A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles

“… 24 BBB permeability is an important pathophysiological process during the stroke. 25 , 26 At the same time, no intracerebral hemorrhage occurred in the FUS group, but different degrees of cerebral hemorrhage occurred when FUS and μBs are combined in the other two groups. Therefore, the presence of both the appropriate ultrasound field and the μBs are necessary for the hemorrhage to occur.…”

“…24 BBB permeability is an important pathophysiological process during the stroke. 25,26 At the same time, no intracerebral hemorrhage occurred in the FUS group, but different degrees of When ICH occurs, the hematoma compresses the surrounding tissue leading to ischemia and hypoxia in the compressed tissue, which causes oxidative stress and oxidative damage in the brain tissue. 27,28 Previous studies have shown that edaravone protects neurons and vascular endothelial cells by scavenging free radicals (such as hydrogen peroxide and hydroxyl radicals) and inhibiting lipid peroxidation.…”

Metformin attenuates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion

“…50 Chronic CBF dysregulation and BBB impairment may change Aβ metabolism and result in a cognitive decline apart from typical vascular dementia. 51 In addition, reparative angiogenesis can reduce white matter lesions and irreversible neuronal injury under chronic hypoperfusion. 52 Previous studies indicate that the occurrence of blood-brain barrier (BBB) leakage is earlier than demyelination, and vascular abnormality may compromise oligodendrogenesis and myelin regeneration in BCAS.…”