In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice

Abstract

We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/α-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [O]-HO positron emission tomography. Glucose metabolism ([F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia.

Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia

“…With increasing time there is a recovery of blood flow in young mice to 15-20% baseline levels at 1 month when measured by laser Doppler ultrasound or laser speckle imaging (36,37). These changes have been attributed to vascular remodelling in young mice (38) but as yet the effects in older (>1 year) mice remain unknown. Blood flow measures are normally conducted using laser speckle or Doppler flowmetry and constrained by limited depth of penetration and the restriction of these techniques to the cortical surface vasculature.…”

Ablation of Vitamin D Signaling Compromises Cerebrovascular Adaptation to Carotid Artery Occlusion in Mice

“…After unilateral carotid artery occlusion (CAO) the intracranial collateral circulation supplied primarily by the contralateral carotid artery represents the first line of defense against cerebral ischemia. The intracranial collateral circulation involves both large vessels of the Willis circle and smaller pial anastomoses between the terminal branches of the anterior, middle, and posterior cerebral arteries [ 15 , 16 , 17 , 18 ]. As vitamin D deficiency has been reported recently to cause marked morphological and functional alterations of cerebral arteries [ 19 , 20 ], we hypothesize that the collateral pathways might also be compromised resulting in an insufficient adaptation of the cerebrocortical circulation to CAO.…”

Non-invasive characterization of amyotrophic lateral sclerosis in a hTDP-43A315T mouse model: A PET-MR study

“…Assessing changes in cerebral blood flow (CBF) yields important information on the onset and progression of various pathological conditions ( Yonas et al, 2005 , Govaerts et al, 2019 , Struys et al, 2017 ). However, up to date, perfusion MRI in animal models of ALS has not been implemented.…”