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Differential effects of intranasal insulin and caffeine on cerebral blood flow.

ABSTRACT: Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task-induced CBF as well as blood oxygenation level-dependent (BOLD) response in the visual cortex using pulsed arterial spin-labeling MRI. An intranasal insulin application was used to avoid peripheral hyperinsulinaemia, which would lead to a cascade of hormonal changes. In a control experiment, caffeine was applied due to its well-known impact on the vasculature of the brain leading to a reliable reduction of CBF. Eight lean subjects were included in the study. On 2 separate days, intranasal human insulin or caffeine tablets were given to the subjects after fasting over night. On each day, basal CBF and task-induced CBF were measured before and 30 min after application of insulin or caffeine in each subject. During the task condition, a flickering checkerboard was presented. Insulin had no effect on basal CBF and task-induced CBF in comparison with drug-free baseline measurement in the visual cortex and control regions. After caffeine application, however, there was a significant decrease of CBF during stimulation in the visual cortex. The BOLD response was not altered by insulin or caffeine between pre- and postdose measurements. In conclusion, we found no evidence for a direct vasodilatory effect of intranasal insulin on the cerebral vascular system in this study.

SUBMITTER: Grichisch Y

PROVIDER: S-EPMC6870137 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Differential effects of intranasal insulin and caffeine on cerebral blood flow.

Grichisch Yuko Y Çavuşoğlu Mustafa M Preissl Hubert H Uludağ Kamil K Hallschmid Manfred M Birbaumer Niels N Häring Hans U HU Fritsche Andreas A Veit Ralf R

Human brain mapping 20110309 2

Insulin is an important modulator of brain functions such as memory and appetite regulation. Besides the effect on neuronal activity, it is also possible that insulin has a direct vasodilatory effect on cerebral blood flow (CBF). We investigated the impact of increased insulin levels in the central nervous system on basal and task-induced CBF as well as blood oxygenation level-dependent (BOLD) response in the visual cortex using pulsed arterial spin-labeling MRI. An intranasal insulin applicatio ...[more]

PMID: 21391271

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Project description:ObjectivesCerebral blood flow (CBF) estimates from arterial spin labelling (ASL) show unexplained variability in older populations. We studied the impact of variation of haematocrit (Hct) on CBF estimates in a tri-ethnic elderly population.Materials and methodsApproval for the study was obtained from the Fulham Research Ethics Committee and participants gave written informed consent. Pseudo-continuous arterial spin labelling was performed on 493 subjects (age 55-90) from a tri-ethnic community-based cohort recruited in London. CBF was estimated using a simplified Buxton equation, with and without correction for Hct measured from blood samples. Differences in perfusion were compared, stratified by sex, ethnicity and diabetes. Results of Student's t tests were reported with effect size.ResultsHct adjustment decreased CBF estimates in all categories except white European men. The decrease for women was 2.7 (3.0, 2.4) mL/100 g/min) (mean (95% confidence interval (CI)), p?<?0.001 d?=?0.38. The effect size differed by ethnicity with estimated mean perfusion in South Asian and African Caribbean women found to be lower by 3.0 (3.6, 2.5) mL/100 g/min, p?<?0.001 d?=?0.56 and 3.1 (3.6, 2.5) mL/100 g/min), p?<?0.001 d?=?0.48, respectively. Estimates of perfusion in subjects with diabetes decreased by 1.8 (2.3, 1.4) mL/100 g/min, p?<?0.001 d?=?0.23) following Hct correction. Correction for individual Hct altered sample frequency distributions of CBF values, especially in women of non-European ethnicity.ConclusionASL-derived CBF values in women, non-European ethnicities and individuals with diabetes are overestimated if calculations are not appropriately adjusted for individual Hct.Key points• CBF quantification from ASL using a fixed Hct of 43.5%, as recommended in the ISMRM white paper, may lead to erroneous CBF estimations particularly in non-European and female subjects. • Individually measured Hct values improve the accuracy of CBF estimation and, if these are not available, an adjusted value according to gender, ethnicity or diabetes status should be considered. • Hct-corrected ASL could be potentially important for CBF threshold decision making in the fields of neurodegenerative disease and neuro-oncology.

Project description:IMPORTANCE:Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE:To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, ?-amyloid (A?), and cognition. DESIGN, SETTING, AND PARTICIPANTS:A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS:3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar A?. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES:Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and A? were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS:The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P?=?.0003), with the largest reductions in the parietal cortex (-37.6%; P?<?.0001) and precuneus (-31.8%; P?=?.0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P?=?.047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P?=?.12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P?=?.60). CONCLUSIONS AND RELEVANCE:In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.

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Differential effects of intranasal insulin and caffeine on cerebral blood flow.

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Differential effects of intranasal insulin and caffeine on cerebral blood flow.

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