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Introduction: The degree of cortical hypoperfusion following carotid steno-occlusion depends on the dynamic compensation from the collateral circulation. The presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack (TIA) in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status among patients with ischemic stroke, it is unclear whether type 2 diabetes (T2DM) specifically affects leptomeningeal collateral flow regulation and the adaptation of collateral vessels at the circle of Willis during hypoperfusion.Methods: Spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal MCA and ACA branches over two weeks following unilateral common carotid artery occlusion (CCAO) were determined by optical coherent tomography in db/+ and db/db mice, a mouse model for obesity and type 2 diabetes. The temporal adaptation of the circle of Willis (CW) following CCAO was assessed by measuring CW vessel diameters.Results: Following unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared to db/+ mice, which coincided with a reduced dilation of distal ACA branches, leading to reduced flow not only in pial vessels, but also in penetrating arterioles bordering the distal MCA and ACA. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the CW, in addition to a delayed post-CCAO adaptive response by one to two weeks compared to db/+ mice.Conclusions: T2DM is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or TIA.