Substantial Reduction of Parenchymal Cerebral Blood Flow in Mice with Bilateral Common Carotid Artery Stenosis.

Yorito Hattori,Satoshi Iguchi,Yumi Yamamoto,Masafumi Ihara,Satoshi Saito,Kazuyuki Nagatsuka,Hidehiro Iida,Jun-Ichiro Enmi

doi:10.1038/srep32179

Yorito Hattori, Satoshi Iguchi + Show 6 more

Open Access

https://doi.org/10.1038/srep32179

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Abstract

The bilateral common carotid artery stenosis (BCAS) mouse model, which replicates chronic cerebral hypoperfusion and white matter ischemic lesions, is considered to model some aspects of vascular cognitive impairment. Cerebral blood flow (CBF) changes in the brain surface post-BCAS have been demonstrated by laser speckle flowmetry, but CBF levels in the brain parenchyma remain unknown. Adult C57BL/6J male mice were subjected to BCAS using external microcoils. Brain magnetic resonance angiography (MRA) was conducted to visualize the intracranial main arteries while arterial spin labeling (ASL) was used to measure cortical and subcortical parenchymal CBF levels before and after BCAS. Brain MRA showed anterior circulation flow was substantially decreased until 14 days post-BCAS, which gradually but incompletely recovered over the following 14 days, with probable growth of collaterals from the posterior cerebral artery. ASL showed that cortical and subcortical parenchymal CBF remained decreased at approximately 50% of the baseline level during 1 and 14 days post-BCAS, recovering to approximately 70% at day 28. CBF levels in the parenchyma were lower than the cortical superficial region in the BCAS model and remained decreased without recovery during the first 2 weeks post-BCAS. These results suggest that the BCAS model reliably replicates chronic cerebral hypoperfusion.

Highlights

Vascular cognitive impairment (VCI) is the second most common form of dementia after Alzheimer’s disease (AD)[1], and the prevalence of mixed dementia with clinical and pathological features of both VCI and AD is increasing as a cause of age-related senile cognitive impairment[2,3]
These results indicate that Cerebral blood flow (CBF) in the anterior circulation was acutely reduced from day 1 after bilateral common carotid artery stenosis (BCAS), but that cortical superficial CBF was more likely gradually compensated for by collateral growth from the posterior to anterior circulation
CBF levels have been monitored using a variety of modalities including laser speckle flowmetry (LSF), arterial spin labeling (ASL), single photon emission computed tomography (SPECT), and 15O-positron emission tomography (PET)

Summary

Introduction

Vascular cognitive impairment (VCI) is the second most common form of dementia after Alzheimer’s disease (AD)[1], and the prevalence of mixed dementia with clinical and pathological features of both VCI and AD is increasing as a cause of age-related senile cognitive impairment[2,3]. To investigate the molecular mechanisms, several rodent models have been established[4], including bilateral common carotid artery stenosis (BCAS) model[5,6,7], reliably demonstrating chronic cerebral hypoperfusion, white matter ischemic damage (e.g., rarefaction and gliosis), and spatial working memory impairment. The CBF profiles in deep brain structures, such as the white matter and caudoputamen, after BCAS surgery remains unknown and, may not replicate those observed in subcortical VCI patients with low cerebral parenchymal CBF especially in the frontal lobe. We hypothesized that parenchymal CBF was lower than the brain surface or subsurface CBF after BCAS surgery and measured regional CBF levels using arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging and brain MR angiography (MRA)

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