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neurovascular reactivity

Therese S Salameh, Gul N Shah, Tulin O Price, Melvin R Hayden, William A Banks
All forms of diabetes mellitus are characterized by chronic hyperglycemia resulting in the development of a number of microvascular and macrovascular pathologies. Diabetes is also associated with changes in brain microvasculature, leading to dysfunctions and ultimately disruption of the blood-brain barrier (BBB). These changes are correlated with a decline in cognitive function. In diabetes, BBB damage is associated with increased oxidative stress and reactive oxygen species (ROS). This occurs because of the increased oxidative metabolism of glucose caused by hyperglycemia...
October 11, 2016: Journal of Pharmacology and Experimental Therapeutics
Evelyn M R Lake, Paolo Bazzigaluppi, James Mester, Lynsie A M Thomason, Rafal Janik, Mary Brown, JoAnne McLaurin, Peter L Carlen, Dale Corbett, Greg J Stanisz, Bojana Stefanovic
Brain plasticity following focal cerebral ischemia has been observed in both stroke survivors and in preclinical models of stroke. Endogenous neurovascular adaptation is at present incompletely understood yet its potentiation may improve long-term functional outcome. We employed longitudinal MRI, intracranial array electrophysiology, Montoya Staircase testing, and immunofluorescence to examine function of brain vessels, neurons, and glia in addition to forelimb skilled reaching during the subacute stage of ischemic injury progression...
September 21, 2016: NeuroImage
Anusha Mishra
Astrocytes are the most common glial cells in the brain with fine processes and endfeet that intimately contact both neuronal synapses and the cerebral vasculature. They play an important role in mediating neurovascular coupling (NVC) via several astrocytic Ca(2+) -dependent signalling pathways such as K(+) release through BK channels, and the production and release of arachidonic acid metabolites. They are also involved in maintaining the resting tone of the cerebral vessels by releasing ATP and COX-1 derivatives...
September 13, 2016: Journal of Physiology
K Kilic, B Aktan, M Sedat-Sakat, A Kızıltunç, O Yoruk
Objective: Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of upper airway obstruction that occur during sleep which leads to cardiovascular, neurovascular and metabolic diseases. The mechanisms of complications in these patients are unclear. In this report, we aimed to determine the cause of oxidative imbalance in patients with OSAS and to evaluate the vascular endothelial dysfunction as a suspect for complications of the disease. Materials and Methods: Fifty patients diagnosed as moderate or severe OSAS (AHI > 15) by polysomnography and 50 healthy volunteers are included in the study...
February 15, 2016: West Indian Medical Journal
Mohammad A Anwar, Ali H Eid
Stroke and other neurovascular derangements are main causes of global death. They, along with spinal cord injuries, are responsible for being the principal cause of disability due to neurological and cognitive problems. These problems then lead to a burden on scarce financial resources and societal care facilities as well as have a profound effect on patients' families. The mechanism of action in these debilitating diseases is complex and unclear. An important component of these problems arises from derangement of blood vessels, such as blockage due to clotting/embolism, endothelial dysfunction, and overreactivity to contractile agents, as well as alteration in endothelial permeability...
2016: Methods in Molecular Biology
Dimitrios Baltzis, Jody R Dushay, Jordan Loader, Jim Wu, Robert L Greenman, Matthieu Roustit, Aristidis Veves
CONTEXT: The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, possesses pleiotropic vasodilatory, antioxidant, and anti-inflammatory properties in animals, independent of its glucose-lowering properties. While large randomized clinical trials are being conducted to better evaluate the efficacy and safety of linagliptin on cardiovascular outcomes, little is known about its effects on vascular function in humans. OBJECTIVE: To evaluate the effect of linagliptin on surrogates of vascular and mitochondrial function...
September 1, 2016: Journal of Clinical Endocrinology and Metabolism
Erin L Mazerolle, Yuhan Ma, David Sinclair, G Bruce Pike
Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies of patients with cerebrovascular disease have largely ignored the confounds associated with abnormal cerebral blood flow, vascular reactivity and neurovascular coupling. We studied BOLD fMRI activation and cerebrovascular reactivity in moyamoya disease. To characterize the impact of remote vascular demands on BOLD fMRI measurements, we varied the vascular territories engaged by manipulating the experimental task performed by the participants...
August 30, 2016: Clinical Physiology and Functional Imaging
Michael K Schuhmann, Miloš Krstić, Christoph Kleinschnitz, Felix Fluri
Fingolimod (FTY720) a functional sphingosine-1-phosphate receptor 1 (S1P1) antagonist reduces infarct volume and improves neurological deficits in different rodent stroke models by modulating inflammatory and immune processes. However, studies on FTY720 regarding its non-immunological efficacy on ischemic cerebral tissue are sparse. Here we investigated whether FTY720 has cytoprotective and restorative properties following ischemic stroke in mice. Male C57Bl/6 mice received FTY720 (1mg/kg) or a vehicle solution intraperitoneally immediately prior to transient middle cerebral artery occlusion (tMCAO; 30 min...
August 23, 2016: Current Neurovascular Research
Ulrich Lindberg, Nanna Witting, Stine Lundgaard Jørgensen, John Vissing, Egill Rostrup, Henrik Bo Wiberg Larsson, Christina Kruuse
Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in muscles. This causes functional ischemia and contributes to muscle wasting. Similar functional ischemia may be present in brains of patients with BMD, who often have mild cognitive impairment, and nNOS may be important for the regulation of the microvascular circulation in the brain. We hypothesized that treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates nitric oxide responses, would augment both the blood oxygen level-dependent (BOLD) response and cerebral blood flow (CBF) in patients with BMD...
August 2, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Panayiota Papadopoulos, Xin-Kang Tong, Hans Imboden, Edith Hamel
Alterations of the renin-angiotensin system have been implicated in the pathogenesis of Alzheimer's disease. We tested the efficacy of losartan (10 mg/kg/day for three months), a selective angiotensin II type 1 receptor antagonist, in alleviating cerebrovascular and cognitive deficits in double-transgenic mice (six months at endpoint) that overexpress a mutated form of the human amyloid precursor protein (APPSwe,Ind) and a constitutively active form of the transforming growth factor-β1, thereafter named A/T mice...
July 7, 2016: Journal of Cerebral Blood Flow and Metabolism
Hatice Gamze Poyrazoglu, Umit Erkan Vurdem, Alev Arslan, Salih Uytun
Migraine is a commonly seen neurovascular disorder during childhood. Inflammation induced by the activation of cytokines and neuropeptides is implied in its pathophysiology. There is an association between inflammation and atherosclerosis in patients with migraine. In addition, there is a strong correlation between early atherosclerotic wall lesions and carotid intima-media thickness (CIMT). The study population consisted of 57 migraine patients aged 5-17 years, as well as 47 healthy children who served as the control group...
October 2016: Neurological Sciences
Jeongeun Sim, Areum Jo, Bok-Man Kang, Sohee Lee, Oh Young Bang, Chaejeong Heo, Gil-Ja Jhon, Youngmi Lee, Minah Suh
Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals...
June 2016: Experimental Neurobiology
Rami Bou Khalil, Elie Khoury, Salam Koussa
Alzheimer's disease (AD) is a chronic neurodegenerative disorder presenting as progressive cognitive decline with dementia that does not, to this day, benefit from any disease-modifying drug. Multiple etiologic pathways have been explored and demonstrate promising solutions. For example, iron ion chelators, such as deferoxamine, are a potential therapeutic solution around which future studies are being directed. Another promising domain is related to thrombin inhibitors. In this minireview, a common pathophysiological pathway is suggested for the pathogenesis of AD to prove that all these mechanisms converge onto the same cascade of neuroinflammatory events...
June 22, 2016: World Journal of Psychiatry
Shikha Prasad, Ravi K Sajja, Mohammad A Kaisar, Luca Cucullo
In this study, we sought to investigate how concomitant hyperglycemia influences the impact of combination antiretroviral therapy on blood-brain barrier (BBB) endothelial function. Immortalized human brain microvascular endothelial cell line (hCMEC/D3) was exposed to azidothymidine (AZT; a nucleoside reverse transcriptase inhibitor) and/or indinavir (IND; protease inhibitor) in normal glycemic (5.5mM) or hyperglycemic (HG; 25mM) media containing D-glucose for 24-72h. Cellular reactive oxygen species (ROS) and mitochondria-specific superoxide levels were assayed in addition to membrane potential to determine the extent of mitochondrial dysfunction...
June 23, 2016: Neurotoxicology
Kyle T S Pattinson, Richard G Wise
Opioid analgesia is limited by the potentially fatal side effect of respiratory depression. In humans the brain mechanisms of opioid-induced respiratory depression are poorly understood. Investigating pharmacological influences upon breathing helps us to understand better the brain's respiratory control networks. Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (FMRI) maps neuronal activity in the brain, and is therefore a potentially useful, noninvasive technique to investigate the functional neuroanatomy of respiratory control in humans...
2016: Advances in Experimental Medicine and Biology
Craig D Steinback, Marc J Poulin
The brain is a vital organ that relies on a constant and adequate supply of blood to match oxygen and glucose delivery with the local metabolic demands of active neurones. It is well established that cerebral blood flow is altered in response to both neural activity and humoral stimuli. Thus, augmented neural activation (e.g. visual stimulation) leads to locally increased cerebral blood flow via functional hyperaemia, whereas humoral stimuli (i.e. alterations in arterial PO2 and PCO2) produce global increases in cerebral blood flow...
2016: Advances in Experimental Medicine and Biology
Pei-Yu Lin, Shih-Jung Peng, Chia-Ning Shen, Pankaj J Pasricha, Shiue-Cheng Tang
Pericytes and glial cells are accessory cells of neurovascular networks, which have been reported to participate in scar formation after tissue injury. However, it remains unclear whether similar reactive cellular responses occur in pancreatic intraepithelial neoplasia (PanIN). In this study we developed three-dimensional (3D) duct lesion histology to investigate PanIN and the associated pericyte, glial, and islet remodeling. Transparent mouse pancreata with a Kras(G12D) mutation were used to develop 3D duct lesion histology...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Aaron Dadas, Nicola Marchi, Damir Janigro
Over the past decades, the significance of cytochrome P450 (CYP) enzymes has expanded beyond their role as peripheral drug metabolizers in the liver and gut. CYP enzymes are also functionally active at the neurovascular interface. CYP expression is modulated by disease states, impacting cellular functions, detoxification, and reactivity to toxic stimuli and brain drug biotransformation. Unveiling the physiological and molecular complexity of brain P450 enzymes will improve our understanding of the mechanisms underlying brain drug availability, pharmacological efficacy, and neurotoxic adverse effects from pharmacotherapy targeting brain disorders...
June 13, 2016: Drug Discovery Today
Olga Marshall, Sanjeev Chawla, Hanzhang Lu, Louise Pape, Yulin Ge
Cerebrovascular reactivity measures vascular regulation of cerebral blood flow and is responsible for maintaining healthy neurovascular coupling. Multiple sclerosis exhibits progressive neurodegeneration and global cerebrovascular reactivity deficits. This study investigates varied degrees of cerebrovascular reactivity impairment in different brain networks, which may be an underlying cause for functional changes in the brain, affecting long-distance projection integrity and cognitive function; 28 multiple sclerosis and 28 control subjects underwent pseudocontinuous arterial spin labeling perfusion MRI to measure cerebral blood flow under normocapnia (room air) and hypercapnia (5% carbon dioxide gas mixture) breathing...
June 15, 2016: Journal of Cerebral Blood Flow and Metabolism
Paulo W Pires, Fabrice Dabertrand, Scott Earley
Intracerebral parenchymal arterioles (PAs), which include parenchymal arterioles, penetrating arterioles and pre-capillary arterioles, are high resistance blood vessels branching out from pial arteries and arterioles and diving into the brain parenchyma. Individual PA perfuse a discrete cylindrical territory of the parenchyma and the neurons contained within. These arterioles are a central player in the regulation of cerebral blood flow both globally (cerebrovascular autoregulation) and locally (functional hyperemia)...
2016: Journal of Visualized Experiments: JoVE
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