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Comparison of cerebral and cutaneous microvascular dysfunction with the development of type 1 diabetes.

ABSTRACT: Rationale: Diabetes can lead to cerebral and cutaneous vascular dysfunction. However, it is still unclear how vascular function changes with the development of diabetes and what differences exist between cerebral and cutaneous vascular dysfunction. Thus, it is very important to monitor changes in cerebral and cutaneous vascular function responses in vivo and study their differences during diabetes development. Methods: With the assistance of newly developed skull and skin optical clearing techniques, we monitored the responses of sodium nitroprusside (SNP)- and acetyl choline (ACh)-induced cerebral and cutaneous vascular blood flow and blood oxygen in diabetic mice in vivo during the development of type 1 diabetes (T1D) by combining laser speckle contrast imaging with hyperspectral imaging. We then compared the differences between cerebral and cutaneous vascular responses and explored the reasons for abnormal changes induced in response to different vascular beds. Results: In the early stage of diabetes (T1D-1 week), there were abnormal changes in the cerebral vascular blood flow and blood oxygen responses to SNP and ACh as well as cutaneous vascular blood oxygen. The cutaneous vascular blood flow response also became abnormal from T1D-3 weeks. Additionally, the T1D-induced abnormal blood flow response was associated with changes in vascular myosin light chain phosphorylation and muscarinic acetylcholine receptor M3 levels, and the aberrant blood oxygen response was related to an increase in glycated hemoglobin levels. Conclusion: These results suggest that the abnormal cutaneous vascular blood oxygen response occurred earlier than the blood flow response and therefore has the potential to serve as a good assessment indicator for revealing cerebrovascular dysfunction in the early stage of diabetes.

SUBMITTER: Feng W

PROVIDER: S-EPMC6735377 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Comparison of cerebral and cutaneous microvascular dysfunction with the development of type 1 diabetes.

Feng Wei W Liu Shaojun S Zhang Chao C Xia Qing Q Yu Tingting T Zhu Dan D

Theranostics 20190812 20

Rationale: Diabetes can lead to cerebral and cutaneous vascular dysfunction. However, it is still unclear how vascular function changes with the development of diabetes and what differences exist between cerebral and cutaneous vascular dysfunction. Thus, it is very important to monitor changes in cerebral and cutaneous vascular function responses in vivo and study their differences during diabetes development. Methods: With the assistance of newly developed skull and skin op ...[more]

PMID: 31534524

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Project description:Patients with Alzheimer's disease (AD) often have cerebral white matter (WM) hyperintensities on MRI and microinfarcts of presumed microvascular origin pathologically. Here, we determined if vasodilator dysfunction of WM-penetrating arterioles is associated with pathologically defined WM injury and disturbances in quantitative MRI-defined WM integrity in patients with mixed microvascular and AD pathology. We analyzed tissues from 28 serially collected human brains from research donors diagnosed with varying degrees of AD neuropathologic change (ADNC) with or without cerebral microinfarcts (mVBI). WM-penetrating and pial surface arteriolar responses to the endothelium-dependent agonist bradykinin were quantified ex vivo with videomicroscopy. Vascular endothelial nitric oxide synthase (eNOS) and NAD(P)H-oxidase (Nox1, 2 and 4 isoforms) expression were measured with quantitative PCR. Glial fibrillary acidic protein (GFAP)-labeled astrocytes were quantified by unbiased stereological approaches in regions adjacent to the sites of WM-penetrating vessel collection. Post-mortem diffusion tensor imaging (DTI) was used to measure mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA), quantitative indices of WM integrity. In contrast to pial surface arterioles, white matter-penetrating arterioles from donors diagnosed with high ADNC and mVBI exhibited a significantly reduced dilation in response to bradykinin when compared to the other groups. Expression of eNOS was reduced, whereas Nox1 expression was increased in WM arterioles in AD and mVBI cases. WM astrocyte density was increased in AD and mVBI, which correlated with a reduced vasodilation in WM arterioles. Moreover, in cases with low ADNC, bradykinin-induced WM arteriole dilation correlated with lower ADC and higher FA values. Comorbid ADNC and mVBI appear to synergistically interact to selectively impair bradykinin-induced vasodilation in WM-penetrating arterioles, which may be related to reduced nitric oxide- and excess reactive oxygen species-mediated vascular endothelial dysfunction. WM arteriole vasodilator dysfunction is associated with WM injury, as supported by reactive astrogliosis and MRI-defined disrupted WM microstructural integrity.

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Comparison of cerebral and cutaneous microvascular dysfunction with the development of type 1 diabetes.

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Comparison of cerebral and cutaneous microvascular dysfunction with the development of type 1 diabetes.

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