Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Dandona, Paresh; James, Ian; Newbury, P.; Woollard, Malcolm; Beckett, A. Gordon

doi:10.1136/bmj.2.6133.325

Cited by 151 publications

(100 citation statements)

References 4 publications

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“…Compromised CR has been reported in diabetic patients. 38,39 These findings support the notion that there is endothelial dysfunction in diabetes. TgeNOS mice showed reduced hypercapnic response compared with wild-type mice but did not reach statistical significance.…”

Section: Cerebrovascular Reactivitysupporting

confidence: 80%

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice

Chandra

Mohan

Ford

et al. 2015

J Cereb Blood Flow Metab

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Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2 Akitaþ/À ), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2Akitaþ/À ) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2Akitaþ/À and TgeNOS-Ins2 Akitaþ/À were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2Akitaþ/À mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2 Akitaþ/À was significantly higher compared with the Ins2Akitaþ/À and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target.

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Section: Cerebrovascular Reactivitysupporting

confidence: 80%

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice

Chandra

Mohan

Ford

et al. 2015

J Cereb Blood Flow Metab

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“…The regional differences in cerebral metabolic capacity may explain increased sensitivity to hyperglycemia in the cerebral cortex (28). Previous studies described reduced or normal CO 2 reactivity in diabetes (32,33). This study applying CASL for evaluation of CBF and CO 2 vasoreactivity demonstrated that CASL is a reliable tool for assessment of flow reserve in an elderly diabetic population.…”

Section: Regional Perfusion and Brain Volumes In Diabetesmentioning

confidence: 83%

Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity

et al. 2007

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OBJECTIVE -The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation.RESEARCH DESIGN AND METHODS -CBF was examined in 26 diabetic (aged 61.6 Ϯ 6.6 years) and 25 control (aged 60.4 Ϯ 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO 2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla.RESULTS -The diabetic group had smaller global white (P ϭ 0.006) and gray (P ϭ 0.001) matter and larger CSF (36.3%, P Ͻ 0.0001) volumes than the control group. Regional differences were observed for white matter (Ϫ13.1%, P ϭ 0.0008) and CSF (36.3%, P Ͻ 0.0001) in the frontal region, for CSF (20.9%, P ϭ 0.0002) in the temporal region, and for gray matter (Ϫ3.0%, P ϭ 0.04) and CSF (17.6%, P ϭ 0.01) in the parieto-occipital region. Baseline regional CBF (P ϭ 0.006) and CO 2 reactivity (P ϭ 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P Ͻ 0.0001). Higher A1C was associated with lower CBF (P Ͻ 0.0001) and greater CSF (P ϭ 0.002) within the temporal region.CONCLUSIONS -Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes. Diabetes Care 30:1193-1199, 2007D iabetes is a prevalent condition associated with substantial morbidity attributed to vascular complications (1). Diabetes alters endothelial function (2) and permeability of the bloodbrain barrier, thus affecting microcirculation and regional metabolism (3).Studies in type 1 diabetes have shown that the fronto-temporal cortex and periventricular white matter (3) are more affected by diabetic metabolic disturbance. Single proton emission computed tomography (SPECT) studies suggest that chronic hyperglycemia alters cerebral blood flow (CBF) in the frontal, temporal, parietal, occipital, and cerebellar regions of interest (ROIs) (4,5). Vasoreactivity to acetazolamide is not homogeneous, with a majority of hypoperfused and some hyperperfused ROIs (6). White matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI) (7) have been associated with arteriolosclerosis, arising as consequences of aging, diabetes, and other cardiovascular risk factors (8,9). Vascular and neurodegenerative changes in these structures have consequences for regional perfusion, cognitive impairment, and balance in elderly people with type 2 diabetes (10,...

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“…16,17 One of the possible causes of increased postoperative neurologic deficits in diabetic patients is impaired cerebrovascular circulatory and vasodilatory reserve. 18,19 Hyperglycemia leads to impaired vascular function by altering endothelial cell function. The pathway that appears most affected by DM is that of nitric oxide 20 and CPB might alter the cerebral endothelial function more extensively in diabetic patients than in non-diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus Does Not Affect Jugular Bulb Oxygen Saturation in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery

Kim

Shim

et al. 2008

Circ J

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Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Cited by 151 publications

References 4 publications

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice

Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity

Diabetes Mellitus Does Not Affect Jugular Bulb Oxygen Saturation in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery

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Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity.

Cited by 151 publications

References 4 publications

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice

Global and Regional Effects of Type 2 Diabetes on Brain Tissue Volumes and Cerebral Vasoreactivity

Diabetes Mellitus Does Not Affect Jugular Bulb Oxygen Saturation in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery

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Product

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Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2^Akita-type-1 diabetic mice