scholarly journals Nox2 Deficiency Prevents Hypertension-Induced Vascular Dysfunction and Hypertrophy in Cerebral Arterioles

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Siu-Lung Chan ◽  
Gary L. Baumbach
Keyword(s):  
Nadph Oxidase ◽  
Ex Vivo ◽  
Vascular Dysfunction ◽  
Vascular Diseases ◽  
Cross Sectional ◽  
Cranial Window ◽  
Cerebral Arterioles ◽  
The Right ◽  
The Brain

Oxidative stress is involved in many hypertension-related vascular diseases in the brain, including stroke and dementia. Thus, we examined the role of genetic deficiency of NADPH oxidase subunit Nox2 in the function and structure of cerebral arterioles during hypertension. Arterial pressure was increased in right-sided cerebral arterioles with transverse aortic banding for 4 weeks in 8-week-old wild-type (WT) and Nox2-deficient (-/y) mice. Mice were givenNG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) or vehicle to drink. We measured the reactivity in cerebral arterioles through open cranial window in anesthetized mice and wall cross-sectional area and superoxide levelsex vivo. Aortic constriction increased systolic and pulse pressures in right-sided carotid arteries in all groups of mice. Ethidium fluorescence showed increased superoxide in right-sided cerebral arterioles in WT, but not in Nox2-/y mice. Dilation to acetylcholine, but not sodium nitroprusside, was reduced, and cross-sectional areas were increased in the right-sided arterioles in WT, but were unchanged in Nox2-/y mice. L-NAME reduced dilation to acetylcholine but did not result in hypertrophy in right-sided arterioles of Nox2-/y  mice. In conclusion, hypertension-induced superoxide production derived from Nox2-containing NADPH oxidase promotes hypertrophy and causes endothelial dysfunction in cerebral arterioles, possibly involving interaction with nitric oxide.

Responses of cerebral arterioles to ADP: eNOS-dependent and eNOS-independent mechanisms

2004 ◽  
Vol 287 (6) ◽  
pp. H2871-H2876 ◽  
Author(s):  
Frank M. Faraci ◽  
Cynthia Lynch ◽  
Kathryn G. Lamping
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Intercellular Signaling ◽  
Cerebral Microvessels ◽  
Cranial Window ◽  
Independent Mechanism ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
The Brain

ADP mediates platelet-induced relaxation of blood vessels and may function as an important intercellular signaling molecule in the brain. We used pharmacological and genetic approaches to examine mechanisms that mediate responses of cerebral arterioles to ADP, including the role of endothelial nitric oxide synthase (eNOS). We examined responses of cerebral arterioles (control diameter ∼30 μm) in anesthetized wild-type (WT, eNOS+/+) and eNOS-deficient (eNOS−/−) mice using a cranial window. In WT mice, local application of ADP produced vasodilation that was not altered by indomethacin but was reduced by ∼50% by NG-nitro-l-arginine (l-NNA) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (inhibitors of NOS and soluble guanylate cyclase, respectively). In eNOS−/− mice, responses to ADP were largely preserved, and a significant component of the response was resistant to l-NNA (a finding similar to that in WT mice treated with l-NNA). In the absence of l-NNA, responses to ADP were markedly reduced by charybdotoxin plus apamin [inhibitors of Ca2+-dependent K+ channels and responses mediated by endothelium-derived hyperpolarizing factor (EDHF)] in both WT and eNOS−/− mice. Thus pharmacological and genetic evidence suggests that a significant portion of the response to ADP in cerebral microvessels is mediated by a mechanism independent of eNOS. The eNOS-independent mechanism is functional in the absence of inhibited eNOS and most likely is mediated by an EDHF.

scholarly journals Association between Hippocampal Volume and Working Memory in 10,000+ 9–10-Year-Old Children: Sex Differences

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 411
Author(s):  
Shervin Assari ◽  
Shanika Boyce ◽  
Tanja Jovanovic
Keyword(s):  
Working Memory ◽  
Sex Differences ◽  
Parental Education ◽  
Predictor Variable ◽  
National Sample ◽  
Hippocampal Volume ◽  
Study Data ◽  
Cross Sectional ◽  
The Right

Aim: This study tested sex differences in the association between hippocampal volume and working memory of a national sample of 9–10-year-old children in the US. As the hippocampus is functionally lateralized (especially in task-related activities), we explored the results for the right and the left hippocampus. Methods: This is a cross-sectional study using the Adolescent Brain Cognitive Development (ABCD) Study data. This analysis included baseline ABCD data (n = 10,093) of children between ages 9 and 10 years. The predictor variable was right and left hippocampal volume measured by structural magnetic resonance imaging (sMRI). The primary outcome, list sorting working memory, was measured using the NIH toolbox measure. Sex was the moderator. Age, race, ethnicity, household income, parental education, and family structure were the covariates. Results: In the overall sample, larger right (b = 0.0013; p < 0.001) and left (b = 0.0013; p < 0.001) hippocampal volumes were associated with higher children’s working memory. Sex had statistically significant interactions with the right (b = −0.0018; p = 0.001) and left (b = −0.0012; p = 0.022) hippocampal volumes on children’s working memory. These interactions indicated stronger positive associations between right and left hippocampal volume and working memory for females compared to males. Conclusion: While right and left hippocampal volumes are determinants of children’s list sorting working memory, these effects seem to be more salient for female than male children. Research is needed on the role of socialization, sex hormones, and brain functional connectivity as potential mechanisms that may explain the observed sex differences in the role of hippocampal volume as a correlate of working memory.

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

scholarly journals Reducing future fears by suppressing the brain mechanisms underlying episodic simulation

2016 ◽  
Vol 113 (52) ◽  
pp. E8492-E8501 ◽  
Author(s):  
Roland G. Benoit ◽  
Daniel J. Davies ◽  
Michael C. Anderson
Keyword(s):  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Ventromedial Prefrontal Cortex ◽  
Episodic Simulation ◽  
Dorsolateral Prefrontal ◽  
Future Events ◽  
The Right ◽  
Development Of Anxiety ◽  
The Brain

Imagining future events conveys adaptive benefits, yet recurrent simulations of feared situations may help to maintain anxiety. In two studies, we tested the hypothesis that people can attenuate future fears by suppressing anticipatory simulations of dreaded events. Participants repeatedly imagined upsetting episodes that they feared might happen to them and suppressed imaginings of other such events. Suppressing imagination engaged the right dorsolateral prefrontal cortex, which modulated activation in the hippocampus and in the ventromedial prefrontal cortex (vmPFC). Consistent with the role of the vmPFC in providing access to details that are typical for an event, stronger inhibition of this region was associated with greater forgetting of such details. Suppression further hindered participants’ ability to later freely envision suppressed episodes. Critically, it also reduced feelings of apprehensiveness about the feared scenario, and individuals who were particularly successful at down-regulating fears were also less trait-anxious. Attenuating apprehensiveness by suppressing simulations of feared events may thus be an effective coping strategy, suggesting that a deficiency in this mechanism could contribute to the development of anxiety.

Consciousness Emanates from the Neuronal Network of Coordination, A Fact Endorsed by Preserved Consciousness in Focal Ischemic Infarctions

2021 ◽  
Vol 19 (3) ◽  
pp. 17-25
Author(s):  
Dr. Sohail Adnan ◽  
Dr. Mubasher Shah ◽  
Dr. Syed Fahim Shah ◽  
Dr. Fahad Naim ◽  
Dr. Akhtar Ali ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Network ◽  
Brain Activity ◽  
Cross Sectional Study ◽  
Difficult Problem ◽  
Altered Consciousness ◽  
Cross Sectional ◽  
Consciousness Disorder ◽  
The Right ◽  
The Brain

Background: Consciousness has remained a difficult problem for the scientists to explore its relationship to the brain activity. This is the first paper that presents the significance of focal areas of the cerebral cortex for consciousness. Objectives: To determine if consciousness is produced by the activity of the whole brain or one of its focal areas. Methods: We have performed a prospective cross-sectional study in eighty patients of acute ischemic stroke. The neurovascular territory of the middle cerebral artery (MCA) was sectioned into four similar areas. The association of any of these focal areas to consciousness was observed after their dysfunction with ischemic strokes. Results: Of the eighty patients, 57.5 % were males and 42.5 % were females. Mean age was 63 years ± 7 SD. The righthanded patients were 90 % (72) of the whole sample. Focal areas of the right MCA were generally less prone to consciousness disorder. Average statistics of the focal infarctions of the right MCA showed no tendency for consciousness disorder on the Glasgow coma scale (GCS) [Mean GCS of all focal areas; 14.5, SD; 0.71, 95 % CI; 14.27 to 14.72, P= 0.0000004]. Altered consciousness with focal infarctions of the territory of left MCA was also less likely [Mean GCS of all focal areas; 14.2, SD; 1.01, 95 % CI; 13.88 to 14.51, P= 0.0004]. Conclusion: Consciousness is not determined by the activity of a focal area of the cerebral cortex. Perhaps, we get our consciousness from the activity of “Neuronal Network of Coordination”.

scholarly journals Matrix Metalloproteinase-1 Gene Polymorphism Associated with Ultrasound-Assessed Carotid Thickness among Older Adults

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Gilberto Santos Morais Junior ◽  
Nathalia Oliveira Rodrigues ◽  
Adriane Dallanora Henriques ◽  
Audrey Cecília Tonet-Furioso ◽  
Ciro José Brito ◽  
...  
Keyword(s):  
Vascular Diseases ◽  
Intima Media Thickness ◽  
Wall Thickening ◽  
Cross Sectional ◽  
Media Thickness ◽  
Matrix Metalloproteinase 1 ◽  
Cerebrovascular Events ◽  
Significant Difference ◽  
The Right

Background and Aim. Due to the high incidence of vascular diseases, it is necessary to identify new circulating or structural markers for predicting risk for chronic diseases. Some studies suggest that MMP1 gene polymorphisms are associated with the enzyme expression levels in situ (e.g., in atherosclerotic plaques). Objectives. Thus, the study of this polymorphism may help understanding the pathophysiology of coronary disease. Methods. We performed cross-sectional clinical and laboratory evaluations (including measurement of intima-media thickness of carotid arteries) and genotyping of the MMP1 SNP rs495366 (A/G) in 366 elderly people. Results. No significant differences between genotypes were noted for biochemical, metabolic, inflammatory, or clinical variables except for a significant difference in intima-media thickness for the left carotid artery and a trend toward significance for the right counterpart. Conclusion. Carriers of the allele associated with lower MMP1 expression (allele A) presented greater carotid thickness. We suggest that the phenomenon can be explained by impaired remodeling of the arterial wall (poor degradation of collagen fibers in this scenario), yielding carotid wall thickening and a greater intrinsic risk for cerebrovascular events.

Traumatically Induced Brain Stem Hemorrhage and the Computerized Tomographic Scan

Neurosurgery ◽  
1979 ◽  
Vol 4 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Paul R. Cooper ◽  
Kenneth Maravilla ◽  
Joel Kirkpatrick ◽  
Sarah F. Moody ◽  
Frederick H. Sklar ◽  
...  
Keyword(s):  
Ct Scan ◽  
Brain Stem ◽  
Thin Section ◽  
Ex Vivo ◽  
Ct Scanning ◽  
Volume Effect ◽  
Brain Parenchyma ◽  
Ct Scanner ◽  
Cross Sectional ◽  
The Brain

Abstract The computerized tomographic (CT) scan has revolutionized the management of cerebral trauma. Nevertheless, visualization of traumatically induced lesions of the brain stem by the CT scanner remains difficult. Seven patients with autopsy or CT evidence of brain stem hemorrhage were identified over a 1-year period. In six of these patients, brain stem hemorrhage could be defined by CT scan. As part of a prospective study of CT changes after head injury, we performed serial CT scans on six of the seven patients. Clinical experience shows that timing is important for identification of these lesions and that inability to visualize brain stem hematomas may occur because of the development of hematomas after CT scanning, evolution of hemorrhagic lesions that makes them isodense with the surrounding brain stem, patient movement, and technical factors such as the partial volume effect. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.1 ml in volume may be visualized by ex vivo thin section CT scanning techniques. However, the character and anatomical configuration of the hemorrhage may be as important in determining CT visualization as is the volume of the hemorrhage. For example, a hematoma displacing the brain parenchyma was visualized, but a similar-sized small hemorrhage that had diffused through the brain stem tissues was not. Although many of the experimentally placed lesions extended over a rostral-caudal length of 15 mm or more in the brain stem, no lesion was seen on more than three thin section scans. This is explained by the presence of lesions that, although extensive in a rostral-caudal direction, had relatively small cross sectional areas available for identification by the CT scanner. The small size of traumatic lesions of the brain stem and their proximity to bony structures at the base of the skull are not insurmountable obstacles to visualization of brain stem hemorrhages. Serial scanning and the application of thin section computed tomography will lead to identification of most of these lesions.

scholarly journals Neural programming of mesenteric and renal arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H563-H573 ◽  
Author(s):  
John J. Reho ◽  
Xiaoxu Zheng ◽  
James E. Benjamin ◽  
Steven A. Fisher
Keyword(s):  
Smooth Muscle ◽  
Ex Vivo ◽  
Vascular Dysfunction ◽  
Force Production ◽  
Genetically Engineered ◽  
Mesenteric Arteries ◽  
Regulatory Subunit ◽  
Mesenteric Circulation ◽  
Genetically Engineered Mice

There is evidence for developmental origins of vascular dysfunction yet little understanding of maturation of vascular smooth muscle (VSM) of regional circulations. We measured maturational changes in expression of myosin phosphatase (MP) and the broader VSM gene program in relation to mesenteric small resistance artery (SRA) function. We then tested the role of the sympathetic nervous system (SNS) in programming of SRAs and used genetically engineered mice to define the role of MP isoforms in the functional maturation of the mesenteric circulation. Maturation of rat mesenteric SRAs as measured by qPCR and immunoblotting begins after the second postnatal week and is not complete until maturity. It is characterized by induction of markers of VSM differentiation (smMHC, γ-, α-actin), CPI-17, an inhibitory subunit of MP and a key target of α-adrenergic vasoconstriction, α1-adrenergic, purinergic X1, and neuropeptide Y1 receptors of sympathetic signaling. Functional correlates include maturational increases in α-adrenergic-mediated force and calcium sensitization of force production (MP inhibition) measured in first-order mesenteric arteries ex vivo. The MP regulatory subunit Mypt1 E24+/LZ- isoform is specifically upregulated in SRAs during maturation. Conditional deletion of mouse Mypt1 E24 demonstrates that splicing of E24 causes the maturational reduction in sensitivity to cGMP-mediated vasorelaxation (MP activation). Neonatal chemical sympathectomy (6-hydroxydopamine) suppresses maturation of SRAs with minimal effect on a conduit artery. Mechanical denervation of the mature rat renal artery causes a reversion to the immature gene program. We conclude that the SNS captures control of the mesenteric circulation by programming maturation of the SRA smooth muscle.

Vascular injury in diabetic db/db mice is ameliorated by atorvastatin: role of Rac1/2-sensitive Nox-dependent pathways

2014 ◽  
Vol 128 (7) ◽  
pp. 411-423 ◽  
Author(s):  
Thiago Bruder-Nascimento ◽  
Glaucia E. Callera ◽  
Augusto C. Montezano ◽  
Ying He ◽  
Tayze T. Antunes ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Vascular Injury ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction

Our data identify putative molecular mechanisms involving Rac1/2-sensitive, NADPH oxidase (Nox)-dependent pathways, whereby statins may protect against vascular dysfunction in diabetes.

Nurses’ attitudes towards euthanasia in conflict with professional ethical guidelines

2016 ◽  
Vol 24 (1) ◽  
pp. 70-86 ◽  
Author(s):  
Anja Terkamo-Moisio ◽  
Tarja Kvist ◽  
Mari Kangasniemi ◽  
Teuvo Laitila ◽  
Olli-Pekka Ryynänen ◽  
...  
Keyword(s):  
Ethical Guidelines ◽  
Ethical Considerations ◽  
Cross Sectional ◽  
Web Based ◽  
Ethical Approval ◽  
Research Questions ◽  
The Moment ◽  
The Right ◽  
The University

Background: Despite the significant role of nurses in end-of-life care, their attitudes towards euthanasia are under-represented both in the current literature and the controversial debate that is ongoing in several countries. Research questions: What are the attitudes towards euthanasia among Finnish nurses? Which characteristics are associated with those attitudes? Research design: Cross-sectional web-based survey. Participants and research context: A total of 1003 nurses recruited via the members’ bulletin of the Finnish Nurses Association and social media. Ethical considerations: Ethical approval was obtained from the Committee on Research Ethics of the university to which the authors were affiliated. Findings: The majority (74.3%) of the participants would accept euthanasia as part of Finnish healthcare, and 61.8% considered that Finland would benefit from a law permitting euthanasia. Most of the nurses (89.9%) thought that a person must have the right to decide on his or her own death; 77.4% of them considered it likely that they would themselves make a request for euthanasia in certain situations. Discussion: The value of self-determination and the ability to choose the moment and manner of one’s death are emphasized in the nurses’ attitudes towards euthanasia. Conclusion: A continuous dialogue about euthanasia and nurses’ shared values is crucial due to the conflict between nurses’ attitudes and current ethical guidelines on nursing.

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