The Experts below are selected from a list of 1452 Experts worldwide ranked by ideXlab platform

Costantino Iadecola - One of the best experts on this subject based on the ideXlab platform.

  • Hypertension enhances Aβ-induced neurovascular Dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP
    Journal of Cerebral Blood Flow and Metabolism, 2015
    Co-Authors: Giuseppe Faraco, Laibaik Park, Josef Anrather, Ping Zhou, Steven M. Paul, Costantino Iadecola
    Abstract:

    Hypertension (HTN) doubles the risk of Alzheimer’s disease (AD), but the mechanisms remain unclear. Amyloid-β (Aβ), a key pathogenic factor in AD, induces Cerebrovascular Dysfunction. We hypothesiz...

  • cyclooxygenase 1 derived prostaglandin e2 and ep1 receptors are required for the Cerebrovascular Dysfunction induced by angiotensin ii
    Hypertension, 2010
    Co-Authors: Carmen Capone, Josef Anrather, Ping Zhou, Giuseppe Faraco, Costantino Iadecola
    Abstract:

    Prostaglandin E 2 (PGE 2 ) EP1 receptors (EP1Rs) may contribute to hypertension and related end-organ damage. Because of the key role of angiotensin II (Ang II) in hypertension, we investigated the role of EP1R in the Cerebrovascular alterations induced by Ang II. Mice were equipped with a cranial window, and cerebral blood flow was monitored by laser-Doppler flowmetry. The attenuation in cerebral blood flow responses to whisker stimulation (−46±4%) and the endothelium-dependent vasodilator acetylcholine (−40±4%) induced by acute administration of Ang II (250 ng/kg per minute; IV for 30 to 40 minutes) were not observed after cyclooxygenase 1 or EP1R inhibition or in cyclooxygenase 1 or EP1-null mice. In contrast, cyclooxygenase 2 inhibition or genetic inactivation did not prevent the attenuation. Ang II–induced oxidative stress was not observed after cyclooxygenase 1 or EP1R inhibition or in EP1R-null mice. Prostaglandin E 2 reinstated the Ang II–induced Cerebrovascular Dysfunction and oxidative stress after cyclooxygenase 1 inhibition. Brain prostaglandin E 2 levels were not increased by Ang II but were attenuated by cyclooxygenase 1 and not cyclooxygenase 2 inhibition. The Cerebrovascular Dysfunction induced by 14-day administration of “slow-pressor” doses of Ang II (600 ng/kg per minute) was attenuated by neocortical application of SC51089. Cyclooxygenase 1 immunoreactivity was observed in microglia and EP1R in endothelial cells. We conclude that the Cerebrovascular Dysfunction induced by Ang II requires activation of EP1R by constitutive production of prostaglandin E 2 derived from cyclooxygenase 1. The findings provide the first evidence that EP1Rs are involved in the deleterious Cerebrovascular effects of Ang II and suggest new therapeutic approaches to counteract them.

  • hypertension and Cerebrovascular Dysfunction
    Cell Metabolism, 2008
    Co-Authors: Costantino Iadecola, Robin L Davisson
    Abstract:

    Essential hypertension has devastating effects on the brain, being the major cause of stroke and a leading cause of dementia. Hypertension alters the structure of cerebral blood vessels and disrupts intricate vasoregulatory mechanisms that assure an adequate blood supply to the brain. These alterations threaten the cerebral blood supply and increase the susceptibility of the brain to ischemic injury as well as Alzheimer's disease. This review focuses on the mechanisms by which hypertension disrupts cerebral blood vessels, highlighting recent advances and outstanding issues.

  • nadph oxidase derived reactive oxygen species mediate the Cerebrovascular Dysfunction induced by the amyloid β peptide
    The Journal of Neuroscience, 2005
    Co-Authors: Laibaik Park, Josef Anrather, Ping Zhou, Kelly Frys, Rose Pitstick, Steven G Younkin, George A Carlson, Costantino Iadecola
    Abstract:

    Overproduction of the amyloid β (Aβ) peptide is a key factor in the pathogenesis of Alzheimer9s disease (AD), but the mechanisms of its pathogenic effects have not been defined. Patients with AD have Cerebrovascular alterations attributable to the deleterious effects of Aβ on cerebral blood vessels. We report here that NADPH oxidase, the major source of free radicals in blood vessels, is responsible for the Cerebrovascular dysregulation induced by Aβ. Thus, the free-radical production and the associated alterations in vasoregulation induced by Aβ are abrogated by the NADPH oxidase peptide inhibitor gp91ds-tat and are not observed in mice lacking the catalytic subunit of NADPH oxidase (gp91 phox ). Furthermore, oxidative stress and Cerebrovascular Dysfunction do not occur in transgenic mice overexpressing the amyloid precursor protein but lacking gp91 phox . The mechanisms by which NADPH oxidase-derived radicals mediate the Cerebrovascular Dysfunction involve reduced bioavailability of nitric oxide. Thus, a gp91 phox -containing NADPH oxidase is the critical link between Aβ and Cerebrovascular Dysfunction, which may underlie the alteration in cerebral blood flow regulation observed in AD patients.

Xueer Cheng - One of the best experts on this subject based on the ideXlab platform.

  • Reversal of prolonged obesity-associated Cerebrovascular Dysfunction by inhibiting microglial Tak1.
    Nature Neuroscience, 2020
    Co-Authors: Qing Shen, Zhuo Chen, Faming Zhao, Tingting Zhang, Xueer Cheng, Lei Zhang, Shanshan Zhang, Junxia Qi, Juxue Li
    Abstract:

    Prolonged obesity is associated with Cerebrovascular Dysfunction; however, the underlying mechanisms remain largely unclear. In the present study, using a prolonged obesity mouse model that suffers from basilar artery (BA) abnormalities, we find that microglial transforming growth factor β-activated kinase 1 (Tak1) is over-activated in the brainstem. Both pharmacological inhibition primarily in the brainstem and genetic microglia-selective deletion of Tak1 ameliorated BA vascular Dysfunction. Conversely, microglia-specific activation of Tak1 in the brainstem was sufficient to cause an impairment in BA function in chow-fed mice. Mechanistically, Tak1 activation leads to increased interleukin-18 (IL-18) production, whereas blockade of IL-18 receptor in the brain helped protect against Cerebrovascular Dysfunction despite prolonged obesity. Microglia-selective deletion of Tak1 also protects against ischemic stroke in prolonged obesity. Taken together, these findings provide evidence that microglial Tak1 in the brain, and particularly the brainstem, contributes to the pathogenesis of obesity-associated Cerebrovascular Dysfunction. Shen et al. report that prolonged obesity is associated with Cerebrovascular Dysfunction and Tak1 activation in brainstem microglia. Pharmacological inhibition or genetic depletion of Tak1 restores Cerebrovascular function in obese mice.

  • reversal of prolonged obesity associated Cerebrovascular Dysfunction by inhibiting microglial tak1
    Nature Neuroscience, 2020
    Co-Authors: Qing Shen, Zhuo Chen, Faming Zhao, Tingting Zhang, Xueer Cheng
    Abstract:

    Prolonged obesity is associated with Cerebrovascular Dysfunction; however, the underlying mechanisms remain largely unclear. In the present study, using a prolonged obesity mouse model that suffers from basilar artery (BA) abnormalities, we find that microglial transforming growth factor β-activated kinase 1 (Tak1) is over-activated in the brainstem. Both pharmacological inhibition primarily in the brainstem and genetic microglia-selective deletion of Tak1 ameliorated BA vascular Dysfunction. Conversely, microglia-specific activation of Tak1 in the brainstem was sufficient to cause an impairment in BA function in chow-fed mice. Mechanistically, Tak1 activation leads to increased interleukin-18 (IL-18) production, whereas blockade of IL-18 receptor in the brain helped protect against Cerebrovascular Dysfunction despite prolonged obesity. Microglia-selective deletion of Tak1 also protects against ischemic stroke in prolonged obesity. Taken together, these findings provide evidence that microglial Tak1 in the brain, and particularly the brainstem, contributes to the pathogenesis of obesity-associated Cerebrovascular Dysfunction.

David W Busija - One of the best experts on this subject based on the ideXlab platform.

  • Rosuvastatin improves Cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production.
    American Journal of Physiology-heart and Circulatory Physiology, 2005
    Co-Authors: Benedek Erdos, James A Snipes, Allison W Miller, Christina D. Tulbert, Prasad V. G. Katakam, David W Busija
    Abstract:

    Insulin-resistance induces Cerebrovascular Dysfunction and increases the risk for stroke. We investigated whether rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, ca...

  • Cerebrovascular Dysfunction in zucker obese rats is mediated by oxidative stress and protein kinase c
    Diabetes, 2004
    Co-Authors: Benedek Erdos, James A Snipes, Allison W Miller, David W Busija
    Abstract:

    Insulin resistance (IR) impairs vascular function in the peripheral and coronary circulations, but its effects on cerebral arteries are virtually unexplored. We examined the vascular responses of the basilar artery (BA) and its side branches through a cranial window in Zucker lean (ZL) and IR Zucker obese (ZO) rats. Nitric oxide (NO) and K+ channel-mediated dilator responses, elicited by acetylcholine, iloprost, cromakalim, and elevated [K+], were greatly diminished in the ZO rats compared with ZL rats. In contrast, sodium nitroprusside induced similar relaxations in the two experimental groups. Expressions of the K+ channel pore-forming subunits were not affected by IR, while endothelial NO synthase was upregulated in the ZO arteries compared with ZL arteries. Protein kinase C (PKC) activity and production of superoxide anion were increased in the cerebral arteries of ZO rats, and pretreatment with superoxide dismutase restored all examined dilator responses. In contrast, application of PKC inhibitors improved only receptor-linked NO-mediated relaxation, but not K+ channel-dependent responses. Thus, IR induces in ZO rats Cerebrovascular Dysfunction, which is mediated by oxidative stress and partly by PKC activation. The revealed impairment of NO and K+ channel-dependent dilator responses may be responsible for the increased risk of Cerebrovascular events and neurodegenerative disorders in IR.

  • Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebral arteries.
    American Journal of Physiology-heart and Circulatory Physiology, 1999
    Co-Authors: Ferenc Domoki, Roland Veltkamp, Nishadi Thrikawala, Greg Robins, Ferenc Bari, Thomas M. Louis, David W Busija
    Abstract:

    In the newborn, cyclooxygenase (COX)-derived products play an important role in the Cerebrovascular Dysfunction after ischemia-reperfusion (I/R). We examined effects of I/R on expression of COX-1 a...

Jerome Badaut - One of the best experts on this subject based on the ideXlab platform.

  • chronic Cerebrovascular Dysfunction after traumatic brain injury
    Journal of Neuroscience Research, 2016
    Co-Authors: Amandine Jullienne, Andre Obenaus, Aleksandra Ichkova, Catherine Savonabaron, William J Pearce, Jerome Badaut
    Abstract:

    Traumatic brain injuries (TBI) often involve vascular Dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of Cerebrovascular Dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation. We also discuss the mechanisms that mediate these Dysfunctions, focusing on the cellular components of cerebral blood vessels (endothelial cells, smooth muscle cells, astrocytes, pericytes, perivascular nerves) and their known and potential roles in the secondary injury cascade. © 2016 Wiley Periodicals, Inc.© 2016 Wiley Periodicals, Inc. Language: en

Qianhui Shang - One of the best experts on this subject based on the ideXlab platform.

  • dietary curcumin ameliorates aging related Cerebrovascular Dysfunction through the ampk uncoupling protein 2 pathway
    Cellular Physiology and Biochemistry, 2013
    Co-Authors: Yunfei Pu, Hexuan Zhang, Peijian Wang, Yu Zhao, Qiang Li, Qianhui Shang
    Abstract:

    c These authors contributed equally to this work Abstract Background/Aims: Age-related Cerebrovascular Dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating reactive oxygen species (ROS) production. Dietary patterns are widely recognized as contributors to cardiovascular and Cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related Cerebrovascular Dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD) rats and UCP2 knockout (UCP2-/-) and matched wild type mice, were given dietary curcumin (0.2%). The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in Cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired Cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved Cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related Cerebrovascular Dysfunction via the AMPK/UCP2 pathway.

  • Dietary curcumin ameliorates aging-related Cerebrovascular Dysfunction through the AMPK/uncoupling protein 2 pathway.
    Cellular Physiology and Biochemistry, 2013
    Co-Authors: Yunfei Pu, Hexuan Zhang, Peijian Wang, Yu Zhao, Qiang Li, Qianhui Shang
    Abstract:

    c These authors contributed equally to this work Abstract Background/Aims: Age-related Cerebrovascular Dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating reactive oxygen species (ROS) production. Dietary patterns are widely recognized as contributors to cardiovascular and Cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related Cerebrovascular Dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD) rats and UCP2 knockout (UCP2-/-) and matched wild type mice, were given dietary curcumin (0.2%). The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in Cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired Cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved Cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related Cerebrovascular Dysfunction via the AMPK/UCP2 pathway.