Abstract
PurposeA fundamental goal in the drive to understand and find better treatments for dementia is the identification of the factors that render the aging brain vulnerable to neurodegenerative disease. Recent evidence indicates the integrity of the blood–brain barrier (BBB) to be an important component of functional failure underlying age‐related cognitive decline. Practical and sensitive measurement is necessary, therefore, to support diagnostic and therapeutic strategies targeted at maintaining BBB integrity in aging patients. Here, we investigated changes in BBB permeability to endogenous blood water in the aging brain.MethodsA multiple‐echo‐time arterial spin‐labeling MRI technique, implemented on a 9.4T Bruker imaging system, was applied to 7‐ and 27‐month‐old mice to measure changes in water permeability across the BBB with aging.ResultsWe observed that BBB water permeability was 32% faster in aged mice. This occurred along with a 2.1‐fold increase in mRNA expression of aquaporin‐4 water channels and a 7.1‐fold decrease in mRNA expression of α‐syntrophin protein, which anchors aquaporin‐4 to the BBB.ConclusionAge‐related changes to water permeability across the BBB can be captured using noninvasive noncontrast MRI techniques.
Highlights
The blood–brain barrier (BBB) is a dynamic and regulatory interface that protects the brain parenchyma from deleterious infiltration.[1]
The arterial spin-labeling (ASL) signal as a function of TE from the cortical brain region was well-described by a biexponential decay model for each of the mice imaged in this study (Supporting Information Figures S1 and S2)
T2IV in the cortical region was measured to be 13.5 ± 1.2 ms and 11.3 ± 4.1 ms for the aged mice compared with 20.6 ± 1.4 ms and 14.3 ± 4.0 ms for the adult mice, at TI = 800 ms and TI = 1500 ms, respectively
Summary
The blood–brain barrier (BBB) is a dynamic and regulatory interface that protects the brain parenchyma from deleterious infiltration.[1]. The structural integrity of the BBB is typically assessed by capturing the egress of exogenous contrast agents from the blood into the brain parenchyma In patients, this usually involves intravenous delivery of a gadolinium-based contrast agent (GBCA) with dynamic T1-weighted MRI to assess BBB-mediated extravascular GBCA accumulation (known as dynamic contrast-enhanced MRI [DCEMRI]5). This usually involves intravenous delivery of a gadolinium-based contrast agent (GBCA) with dynamic T1-weighted MRI to assess BBB-mediated extravascular GBCA accumulation (known as dynamic contrast-enhanced MRI [DCEMRI]5) These techniques have shown promising results in detecting an increased BBB permeability in patients with the early stages of cognitive impairment in AD.[6] Further studies using GBCA in a novel MRI technique sensitized to vascular water exchange have reported increased water permeability across the BBB in a rat model of AD, when the DCE-MRI permeability measurement did not yet show significant differences between the animal groups.[7] This would imply that measures of water permeability enable measurements of subtle changes to the BBB that occur in the early stages of neurodegenerative disease
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