Carotid Artery Stenting and Blood-Brain Barrier Permeability in Subjects with Chronic Carotid Artery Stenosis.

Arkadiusz Szarmach,Piotr Lass,Pawel Winklewski,Michal Studniarek,Maciej Piskunowicz,Edyta Szurowska,Mariusz Kaszubowski,Grzegorz Halena

doi:10.3390/ijms18051008

Abstract

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (−9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT −16.09%, TTP −7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT −14.65%, TTP −7.46%) sides. PS decreased by almost half: ipsilateral −48.11%, contralateral −45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.

Highlights

Hypertensive/stroke-prone rats with unilateral carotid artery occlusion and a high-salt diet develop white-matter damage similar to that seen in vascular cognitive dementia in humans [1]
This is followed by production of matrix metalloproteinases that disrupt the tight junctions and extracellular matrix resulting in the breakdown of the blood–brain barrier (BBB)
The aim of the study was to assess the short-term effect of carotid artery stenting on BBB permeability in subjects with chronic carotid artery stenosis

Summary

Introduction

Hypertensive/stroke-prone rats with unilateral carotid artery occlusion and a high-salt diet develop white-matter damage similar to that seen in vascular cognitive dementia in humans [1]. Development of white-matter damage in these animals is a multiphase process. Chronic hypertension and the related cerebral vessel lumen narrowing result in loss of normal autoregulation, hypoperfusion, and hypoxia. Hypoxia augments the production of hypoxia inducible factor-1α (HIF-1α), leading to oxidative stress and an inflammatory state. This is followed by production of matrix metalloproteinases that disrupt the tight junctions and extracellular matrix resulting in the breakdown of the blood–brain barrier (BBB). Vasogenic oedema accelerates tissue hypoxia, myelin damage and oligodendrocyte death [1]

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