Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression

Ma, Jiechao; Ayata, Cenk; Huang, Paul L.; Fishman, Mark C.; Moskowitz, Michael A.

doi:10.1152/ajpheart.1996.270.3.h1085

Cited by 85 publications

(91 citation statements)

References 12 publications

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“…NO is basically produced by 3 main enzymes: iNOS, eNOS and nNOS [38]. eNOS has primarily been held responsible for cerebellar artery basal tonus [39], and another study showed that there was ET-1 release in the normal cerebral endothelium [40]. In our study, while the brain eNOS expression levels in the diabetic groups decreased, the ET-1 expression levels were found to be increased.…”

Section: Discussionsupporting

confidence: 45%

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Demir

Çadırcı

Akpınar

et al. 2014

Basic Clin Pharma Tox

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Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/ kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications.Diabetes mellitus (DM) is a severe disease which eventually results in death. During diabetes mellitus, tissues cannot uptake glucose and very severe complications such as nephropathy, retinopathy, neuropathy and peripheral vascular complications occur [1]. Many new mechanisms have been suggested during the formation and progress of these complications. There are studies in many areas, from inflammation to cellular membrane disorders, of the mechanisms of diabetesinduced complications [1][2][3]. There are also many studies on the receptors which are responsible for the formation of diabetes and diabetes-induced complications in relation to our topic: angiotensin receptors, urotensin receptors, glucagon-like peptide 1 receptors and peroxisome proliferator-activated receptora [4,5].Previous studies have shown the importance of angiotensin in diabetes-induced liver damage [6,7], and there are many recent studies showing that endothelin-1 receptors play important roles in diabetes. One study showed that cell proliferation and, at the same time, ET1 production increased in type 2 diabetes [8,9]. Diabetes-related, clinical and experimental studies showed that ET1 plasma levels increased [10,11]. A study by Mastumoto et al. showed that the expression of both ET1 and the receptors increased in the streptozotocin (STZ)-induced diabetes model [12]. In another study, giving endothelin-1 to individuals with insulin resistance reduced endothelin-1-induced vasodilatation [13]. ET1 levels w...

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Section: Discussionsupporting

confidence: 45%

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Demir

Çadırcı

Akpınar

et al. 2014

Basic Clin Pharma Tox

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“…Our study did not measure simultaneously changes in rCBF, which should be done in future experiments. The post-stimulus undershoot of rCBF occurs only in a minority of subjects, is highly variable (Irikura et al, 1994;Ma et al, 1996), task-dependent (Hoge et al, 1999), and can even be explained as an artifact of delayed rCBV changes (Mandeville et al, 1999). Furthermore, the ratio between post-stimulus and stimulus changes of rCBF, as calculated from these studies, reaches only values between approximately 0.15 and 0.3 (Hoge et al 1999;Irikura et al, 1994;Ma et al, 1996).…”

Section: Discussionmentioning

confidence: 71%

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

et al. 2006

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Measuring the hemodynamic response with functional magnetic resonance imaging (fMRI) together with functional near-infrared spectroscopy (fNIRS) may overcome limitations of single-method approaches. Accordingly, we measured the event-related hemodynamic response with both imaging methods simultaneously in young subjects during visual stimulation. An intertrial interval of 60 s was chosen to include the prolonged post-stimulus undershoot of the blood oxygenation level dependent (BOLD) signal. During visual stimulation, the BOLD signal, oxy-, and total hemoglobin (Hb) increased, whereas deoxy-Hb decreased. The post-stimulus period was characterized by an undershoot of the BOLD signal, oxy-Hb, and an overshoot of deoxy-Hb. Total Hb as measured by fNIRS returned to baseline immediately after the end of stimulation. Results suggest that the post-stimulus events as measured by fNIRS are dominated by a prolonged high-level oxygen consumption in the microvasculature. The contribution of a delayed return of blood volume to the BOLD post-stimulus undershoot in post-capillary veins as suggested by the Balloon and Windkessel models remains ambiguous. Temporal changes in the BOLD signal were highly correlated with deoxy-Hb, with lower correlation values for oxy-and total Hb. Furthermore, data show that fNIRS covers the outer 1 cm of the brain cortex. These results were confirmed by simultaneous fMRI/fNIRS measurements during rest. In conclusion, multimodal imaging approaches may contribute to the understanding of neurovascular coupling. D

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“…Future studies should determine how DNA damage responses in astrocytes alter the synthesis/release of these mediators. There is also strong experimental evidence that endothelial NO production contributes to glio-vascular coupling (Chen et al 2014;Girouard et al 2007;Longden and Nelson 2011;Ma et al 1996;Stobart et al 2013; Toth e t a l . 2 0 1 5 b ) .…”

Section: Discussionmentioning

confidence: 99%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow ( C B F ) v i a n e u r o n a l a c t i v i t y -d e p e n d e n t cerebromicrovascular dilation (functional hyperemia) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL/6 mice (3 months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker-stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.

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Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression

Cited by 85 publications

References 12 publications

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Does Bosentan Protect Diabetic Brain Alterations in Rats? The Role of Endothelin‐1 in the Diabetic Brain

Investigating the post-stimulus undershoot of the BOLD signal—a simultaneous fMRI and fNIRS study

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

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