Quantifying alteration of CVR with inflammation and its restoration may inform on novel pathophysiological mechanisms of MS damage and disability, and may lead to the discovery of novel physiological markers of disease status and treatment response. We evaluated CVR in both the GM (CVR GM) and the WM (CVR WM). We tested the hypothesis that CVR is reduced in MS, compared to age and gender-matched controls, as a result of inflammation, and that CVR increases with the reduction of inflammation during immunomodulatory therapy. Here, we evaluated CVR via blood oxygenation level dependent (BOLD) functional MRI (fMRI) during a breath hold (BH) task (a form of hypercapnic stimulus) 12 in a cohort of MS patients with no vascular comorbidities. This impaired regulation of CBF may lead to a state of tissue hypoxia contributing to damage and degeneration 11. Alterations in CVR might be associated with neuroinflammation and neurodegeneration in MS: elevated levels of nitric oxide caused by inflammation may desensitise endothelial and smooth muscle function (vascular habituation), causing decreased vasodilatory capacity 9, 10. The property of reactivity allows blood vessels to regulate blood supply with changes in brain tissue demand for nutrients. This dynamic aspect of vascular function can be investigated through the measurement of cerebrovascular reactivity (CVR), that is, the increase in CBF in response to a vasoactive stimulus, most commonly hypercapnia. While reduced energy supply, as assessed by cerebral blood flow (CBF), has been identified in MS in both the grey matter (GM) and the white matter (WM) 4, 5, 6, 7, the effect of neuroinflammation on the capacity of cerebral circulation to adapt blood supply to changing demand remains largely unexplored 8. Cerebrovascular dysfunction secondary to neuroinflammation may contribute to the pathophysiology of multiple sclerosis (MS) 1, through tissue metabolic alterations, subsequent neurodegeneration and ultimately disability progression 2, 3. The brain’s ability to regulate its local blood supply is key to maintaining brain function and tissue integrity. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring. Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. In patients, a lower pre-treatment CVR GM was associated with a lower GM volume (r = 0.60, p = 0.003). Patients had lower pre-treatment CVR GM ( p = 0.04) and CVR WM ( p = 0.02) compared to HC. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Eighteen age and gender-matched healthy controls (HC) were also assessed. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVR GM and CVR WM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus.
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