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Journal Articles eLife Year : 2021

Cerebral blood flow and cerebrovascular reactivity are preserved in a mouse model of cerebral microvascular amyloidosis

Leon P Munting
Marc Pp Derieppe
Ernst Suidgeest
Lydiane Hirschler
Matthias Jp van Osch
Louise van Der Weerd
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  • PersonId : 1139401

Abstract

Impaired cerebrovascular function is an early biomarker for cerebral amyloid angiopathy (CAA), a neurovascular disease leading to stroke and dementia. The transgenic Swedish Dutch Iowa (Tg-SwDI) mouse model is a model for microvascular CAA, but the extent to which the model reflects similar impairments in cerebrovascular function is not yet fully understood. We used arterial spin labeling (ASL)-MRI and laser Doppler flowmetry (LDF) for extensive functional assessment of the Tg-SwDI brain vasculature using a longitudinal study design. Mice were followed-up until 1 year of age, when extensive amyloid-✂ pathology was visible. Unexpectedly, baseline cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to a hypercapnia challenge in Tg-SwDI mice showed similar estimates as age-matched wild type control mice. The preserved vascular function was found irrespective of the anesthesia protocol applied, i.e., isoflurane or a combination of urethane and-chloralose. Changes in CBF and CVR were however observed as an effect of age and anesthesia. Our findings contradict earlier results obtained in the same mouse model and question to what extent microvascular CAA as seen in Tg-SwDI mice is representative for cerebrovascular dysfunction observed in CAA patients.
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Dates and versions

hal-03453535 , version 1 (28-11-2021)
hal-03453535 , version 2 (04-02-2022)

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Leon P Munting, Marc Pp Derieppe, Ernst Suidgeest, Lydiane Hirschler, Matthias Jp van Osch, et al.. Cerebral blood flow and cerebrovascular reactivity are preserved in a mouse model of cerebral microvascular amyloidosis. eLife, 2021, 10, ⟨10.7554/eLife.61279⟩. ⟨hal-03453535v2⟩
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