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Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.
Abstract The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is thi...
Source: Advances in Pharmacology - October 15, 2014 Category: Drugs & Pharmacology Authors: Lucke-Wold BP, Logsdon AF, Turner RC, Rosen CL, Huber JD Tags: Adv Pharmacol Source Type: research

Blood-brain barrier na transporters in ischemic stroke.
Abstract Blood-brain barrier (BBB) endothelial cells form a barrier that is highly restrictive to passage of solutes between blood and brain. Many BBB transport mechanisms have been described that mediate transcellular movement of solutes across the barrier either into or out of the brain. One class of BBB transporters that is all too often overlooked is that of the ion transporters. The BBB has a rich array of ion transporters and channels that carry Na, K, Cl, HCO3, Ca, and other ions. Many of these are asymmetrically distributed between the luminal and abluminal membranes, giving BBB endothelial cells the abili...
Source: Advances in Pharmacology - October 15, 2014 Category: Drugs & Pharmacology Authors: O'Donnell ME Tags: Adv Pharmacol Source Type: research

Drug delivery to the ischemic brain.
Abstract Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events in neurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary ...
Source: Advances in Pharmacology - October 15, 2014 Category: Drugs & Pharmacology Authors: Thompson BJ, Ronaldson PT Tags: Adv Pharmacol Source Type: research

Combination Approaches to Attenuate Hemorrhagic Transformation After tPA Thrombolytic Therapy in Patients with Poststroke Hyperglycemia/Diabetes.
Abstract To date, tissue type plasminogen activator (tPA)-based thrombolytic stroke therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 5% of stroke patients in the USA. This may be related, in part, to the elevated risk of symptomatic intracranial hemorrhage, and consequently limited therapeutic time window. Clinical investigations demonstrate that poststroke hyperglycemia is one of the most important risk factors that cause intracerebral hemorrhage and worsen neurological outcomes. There is a knowledge gap in understanding the ...
Source: Advances in Pharmacology - October 15, 2014 Category: Drugs & Pharmacology Authors: Fan X, Jiang Y, Yu Z, Yuan J, Sun X, Xiang S, Lo EH, Wang X Tags: Adv Pharmacol Source Type: research

Endothelial Small- and Intermediate-Conductance K Channels and Endothelium-Dependent Hyperpolarization as Drug Targets in Cardiovascular Disease.
Abstract Endothelial calcium/calmodulin-gated K channels of small (KCa2.3) and intermediate conductance (KCa3.1) produce membrane hyperpolarization and endothelium-dependent hyperpolarization (EDH)-mediated vasodilation. Dysfunctions of the two channels and ensuing EDH impairments are found in several cardiovascular pathologies such as diabetes, atherosclerosis, postangioplastic neointima formation, but also inflammatory disease, cancer, and organ fibrosis. Moreover, KCa3.1 plays an important role in endothelial barrier dysfunction, edema formation in cardiac and pulmonary disease, and in ischemic stroke. Concerni...
Source: Advances in Pharmacology - July 29, 2016 Category: Drugs & Pharmacology Authors: Köhler R, Oliván-Viguera A, Wulff H Tags: Adv Pharmacol Source Type: research

The Good and Bad Sides of NAAG.
Abstract Why has such a small peptide been the source of controversy in neuroscience over the last 5 decades? Is N-acetyl-aspartyl-glutamate (NAAG) a neurotransmitter? Is NAAG located in neuronal tissue or in astrocytes? Is NAAG involved in neuropsychiatric and neurodegenerative disorders? Is NAAG therapeutically beneficial in the treatment of stroke or in initiating cascades of events leading to psychosis? After many years of intense research there is no clear consensus within the scientific community on how NAAG behaves in the brain. One of the major controversies about NAAG is its physiological action at N-meth...
Source: Advances in Pharmacology - June 13, 2016 Category: Drugs & Pharmacology Authors: Khacho P, Wang B, Bergeron R Tags: Adv Pharmacol Source Type: research

Estrogens and Coronary Artery Disease: New Clinical Perspectives.
Abstract In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER),...
Source: Advances in Pharmacology - July 29, 2016 Category: Drugs & Pharmacology Authors: Meyer MR, Barton M Tags: Adv Pharmacol Source Type: research

Sphingosine-1-phosphate and Sphingosine-1-phosphate receptors in the cardiovascular system: pharmacology and clinical implications
Adv Pharmacol. 2022;94:95-139. doi: 10.1016/bs.apha.2022.02.001. Epub 2022 Mar 30.ABSTRACTSphingosine-1-phosphate (S1P) is a lipid that binds and activates five distinct receptor subtypes, S1P1, S1P2, S1P3, S1P4, S1P5, widely expressed in different cells, tissues and organs. In the cardiovascular system these receptors have been extensively studied, but no drug acting on them has been approved so far for treating cardiovascular diseases. In contrast, a number of S1P receptor agonists are approved as immunomodulators, mainly for multiple sclerosis, because of their action on lymphocyte trafficking. This chapter summarizes t...
Source: Advances in Pharmacology - June 6, 2022 Category: Drugs & Pharmacology Authors: Simona Federica Spampinato Maria Angela Sortino Salvatore Salomone Source Type: research

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