Abstract
Vitamin D insufficiency has been associated with increased incidence and severity of cerebrovascular disorders. We analyzed the impact of impaired vitamin D signaling on the anatomical and functional aspects of cerebrovascular adaptation to unilateral carotid artery occlusion (CAO), a common consequence of atherosclerosis and cause of ischemic stroke. Cerebrocortical blood flow (CoBF) showed a significantly increased drop and delayed recovery after CAO in mice carrying a functionally inactive vitamin D receptor (VDR) with the most sustained perfusion deficit in the temporal cortex. To identify the cause(s) for this altered adaptation, the extent of compensatory blood flow increase in the contralateral carotid artery and the morphology of pial collaterals between the anterior and middle cerebral arteries were determined. Whereas VDR deficiency had no significant influence on the contralateral carotid arterial blood flow increase, it was associated with decreased number and increased tortuosity of pial anastomoses resulting in unfavorable changes of the intracranial collateral circulation. These results indicate that VDR deficiency compromises the cerebrovascular adaptation to CAO with the most sustained consequences in the temporal cortex. The dysregulation can be attributed to the altered development and function of pial collateral circulation whereas extracranial vessels may not be impaired.
Highlights
Vitamin D is a key regulator of cellular functions and its deficiency has been implicated recently in the development of several diseases including cerebrovascular disorders [1,2,3]
Our results indicate that this compensatory mechanism did not work sufficiently in the absence of vitamin D signaling because the Cerebrocortical blood flow (CoBF) reduction in the temporal cortex was more severe and prolonged
To evaluate the capacity of the intracranial collateral circulation to compensate for the blood loss of the temporal cortex, we examined the pial collaterals between the cortical branches of the middle cerebral artery (MCA) and the anterior cerebral artery (ACA)
Summary
Vitamin D is a key regulator of cellular functions and its deficiency has been implicated recently in the development of several diseases including cerebrovascular disorders [1,2,3]. There are many causes of vitamin D deficiency including reduced synthesis in the skin, decreased bioavailability, decreased synthesis of the active form of vitamin D—1,25-dihydroxyvitamin D—or heritable disorders, such as the hereditary vitamin D resistant rickets (HVDRR) [1]. 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 be compromised resulting in an insufficient adaptation of the cerebrocortical circulation to CAO. The aims of the present study are 1) to determine the consequences of impaired vitamin D signaling in the cerebrovascular adaptation to CAO and 2)
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