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TRPM4-specific blocking antibody attenuates reperfusion injury in a rat model of stroke.
We report the generation of a TRPM4-specific antibody M4P which binds to a region close to the channel pore. M4P could inhibit TRPM4 current and downregulate TRPM4 surface expression, therefore prevent hypoxia-induced cell swelling. In the rat model of 3-h stroke reperfusion, application of M4P at 2 h after occlusion ameliorated reperfusion injury by improving blood-brain barrier integrity, and enhanced functional recovery. Our results demonstrate that TRPM4 blockade could attenuate reperfusion injury in stroke recanalization. When applied together with reperfusion treatments, TRPM4 blocking antibody has the potential to e...
Source: Pflugers Archiv : European Journal of Physiology - October 28, 2019 Category: Physiology Authors: Chen B, Gao Y, Wei S, Low SW, Ng G, Yu D, Tu TM, Soong TW, Nilius B, Liao P Tags: Pflugers Arch Source Type: research

Relevance of stromal interaction molecule 1 (STIM1) in experimental and human stroke
Pflugers Arch. 2021 Nov 10. doi: 10.1007/s00424-021-02636-w. Online ahead of print.ABSTRACTStroke represents a main cause of death and permanent disability worldwide. In the attempt to develop targeted preventive and therapeutic strategies, several efforts were performed over the last decades to identify the specific molecular abnormalities preceding cerebral ischemia and neuronal death. In this regard, mitochondrial dysfunction, autophagy, and intracellular calcium homeostasis appear important contributors to stroke development, as underscored by recent pre-clinical evidence. Intracellular calcium (Ca2+) homeostasis is re...
Source: Pflugers Archiv : European Journal of Physiology - November 10, 2021 Category: Physiology Authors: Rosita Stanzione Maurizio Forte Maria Cotugno Franca Bianchi Simona Marchitti Speranza Rubattu Source Type: research

Stroke: understanding the differences between males and females.
Abstract Stroke is a significant cause of death and long-term disability in the USA. The incidence, mortality, and outcomes of stroke are significantly different between men and women. As with many diseases that affect men and women differently, an understanding on the reasons underlying those differences is critical to effective diagnosis and treatment. This review will examine the sex differences in stroke in both humans and animal models of stroke and review what is known about potential mechanisms underlying these differences. It is clear that there is a complex interaction between hormonal, genetic, and unkno...
Source: Pflugers Archiv : European Journal of Physiology - May 1, 2013 Category: Physiology Authors: Wilson ME Tags: Pflugers Arch Source Type: research

TRPM4 inhibition promotes angiogenesis after ischemic stroke.
Abstract Transient receptor potential melastatin 4 (TRPM4) is a voltage-dependent, nonselective cation channel. Under pathological conditions, sustained activation of TRPM4 leads to oncotic cell death. Here, we report the upregulation of TRPM4 in vascular endothelium following hypoxia/ischemia in vitro and in vivo. In human umbilical vein endothelial cells, TRPM4 expression was increased at both the mRNA and protein levels following oxygen-glucose deprivation. Blocking TRPM4 with 9-phenanthrol greatly enhanced tube formation on Matrigel. In a rat permanent middle cerebral artery occlusion model, TRPM4 was upregula...
Source: Pflugers Archiv : European Journal of Physiology - September 17, 2013 Category: Physiology Authors: Loh KP, Ng G, Yu CY, Fhu CK, Yu D, Vennekens R, Nilius B, Soong TW, Liao P Tags: Pflugers Arch Source Type: research

Involvement of bradykinin in brain edema development after ischemic stroke.
Abstract Stroke is the third leading cause of death in the Western world. Ischemic stroke is characterized by a rapid loss of brain function due to disturbance in the blood supply to a part of the brain. Due to fixed intracranial space, any increase in intracranial fluid volume, or progressive brain edema formation, contributes to further deterioration of the already impaired brain function. Bradykinin increases blood-brain barrier permeability and raises intracranial capillary blood pressure by arterial dilatation and venous constriction leading to brain edema formation. The aim of this paper is to summarize the ...
Source: Pflugers Archiv : European Journal of Physiology - April 23, 2014 Category: Physiology Authors: Dobrivojević M, Spiranec K, Sinđić A Tags: Pflugers Arch Source Type: research

MiRNA-190 exerts neuroprotective effects against ischemic stroke through Rho/Rho-kinase pathway.
This study was to investigate the role of miR-190 in the brain I/R injury. We divided the rats into sham, I/R, control, and miR-190-mim (miR-190 mimics) groups. Quantitative real-time polymerase chain reaction (qRT-PCR), Nissl staining, flow cytometry, and western blot were conducted to examine the expression of miR-190 and cell apoptosis in different groups. The results showed that the expression of miR-190 was greatly decreased in rats suffering with I/R. Overexpression of miR-190 significantly reduced the increased neurological scores, brain water contents, infarct volumes, and neuronal apoptosis in rats suffering with ...
Source: Pflugers Archiv : European Journal of Physiology - November 16, 2020 Category: Physiology Authors: Jiang C, Dong N, Feng J, Hao M Tags: Pflugers Arch Source Type: research

The CNS under pathophysiologic attack-examining the role of K2P channels.
Abstract Members of the two-pore domain K(+) channel (K2P) family are increasingly recognized as being potential targets for therapeutic drugs and could play a role in the diagnosis and treatment of neurologic disorders. Their broad and diverse expression pattern in pleiotropic cell types, importance in cellular function, unique biophysical properties, and sensitivity toward pathophysiologic parameters represent the basis for their involvement in disorders of the central nervous system (CNS). This review will focus on multiple sclerosis (MS) and stroke, as there is growing evidence for the involvement of K2P chann...
Source: Pflugers Archiv : European Journal of Physiology - December 9, 2014 Category: Physiology Authors: Ehling P, Cerina M, Budde T, Meuth SG, Bittner S Tags: Pflugers Arch Source Type: research

Glucose transporters in brain in health and disease.
Abstract Energy demand of neurons in brain that is covered by glucose supply from the blood is ensured by glucose transporters in capillaries and brain cells. In brain, the facilitative diffusion glucose transporters GLUT1-6 and GLUT8, and the Na+-D-glucose cotransporters SGLT1 are expressed. The glucose transporters mediate uptake of D-glucose across the blood-brain barrier and delivery of D-glucose to astrocytes and neurons. They are critically involved in regulatory adaptations to varying energy demands in response to differing neuronal activities and glucose supply. In this review, a comprehensive overview abo...
Source: Pflugers Archiv : European Journal of Physiology - August 12, 2020 Category: Physiology Authors: Koepsell H Tags: Pflugers Arch Source Type: research

Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage.
Abstract Atrial fibrillation (AF) is strongly associated with risk of stroke and heart failure. AF promotes atrial remodeling that increases risk of stroke due to left atrial thrombogenesis, and increases energy demand to support high rate electrical activity and muscle contraction. While many transcriptomic studies have assessed AF-related changes in mRNA abundance, fewer studies have assessed proteomic changes. We performed a proteomic analysis on left atrial appendage (LAA) tissues from 12 patients with a history of AF undergoing elective surgery; atrial rhythm was documented at time of surgery. Proteomic analy...
Source: Pflugers Archiv : European Journal of Physiology - January 16, 2021 Category: Physiology Authors: Rennison JH, Li L, Lin CR, Lovano BS, Castel L, Wass SY, Cantlay CC, McHale M, Gillinov AM, Mehra R, Willard BB, Smith JD, Chung MK, Barnard J, Van Wagoner DR Tags: Pflugers Arch Source Type: research

(H)IF applicable: promotion of neurogenesis by induced HIF-2 signalling after ischaemia
Pflugers Arch. 2021 Jul 12. doi: 10.1007/s00424-021-02600-8. Online ahead of print.ABSTRACTHIF-2 represents a tissue-specific isoform of the hypoxia-inducible factors (HIFs) which regulate oxygen homeostasis in the cell. In acute oxygen deficiency, HIF transcription factors ensure the timely restoration of adequate oxygen supply. Particularly in medical conditions such as stroke, which have a high mortality risk due to ischaemic brain damage, rapid recovery of oxygen supply is of extraordinary importance. Nevertheless, the endogenous mechanisms are often not sufficient to respond to severe hypoxic stress with restoring oxy...
Source: Pflugers Archiv : European Journal of Physiology - July 12, 2021 Category: Physiology Authors: Tristan Leu Joachim Fandrey Timm Schreiber Source Type: research

Sex differences in myocardial metabolism and cardiac function: an emerging concept.
Abstract There is substantial evidence that there are dramatic sex-related differences in the incidence of cardiovascular disease, apparently related to the presence of steroid hormones. This is supported by the discovery of steroid hormone receptors in the heart and vasculature. More controversial is the area of sex-related differences in cardiac metabolism and function. A number of human and animal studies have demonstrated that estrogen and testosterone have cardiac metabolic effects. Additionally, research shows females have higher heart rates and various indices of function, including cardiac output and strok...
Source: Pflugers Archiv : European Journal of Physiology - February 13, 2013 Category: Physiology Authors: Wittnich C, Tan L, Wallen J, Belanger M Tags: Pflugers Arch Source Type: research

Ion transporters in brain endothelial cells that contribute to formation of brain interstitial fluid.
Abstract Ions and water transported across the endothelium lining the blood-brain barrier contribute to the fluid secreted into the brain and are important in maintaining appropriate volume and ionic composition of brain interstitial fluid. Changes in this secretion process may occur after stroke. The present study identifies at transcript and protein level ion transporters involved in the movement of key ions and examines how levels of certain of these alter following oxidative stress. Immunohistochemistry provides evidence for Cl(-)/HCO3 (-) exchanger, AE2, and Na(+), HCO3 (-) cotransporters, NBCe1 and NBCn1, on...
Source: Pflugers Archiv : European Journal of Physiology - September 11, 2013 Category: Physiology Authors: Mokgokong R, Wang S, Taylor CJ, Barrand MA, Hladky SB Tags: Pflugers Arch Source Type: research

The two-pore domain potassium channel KCNK5 deteriorates outcome in ischemic neurodegeneration.
Abstract Potassium channels can fulfill both beneficial and detrimental roles in neuronal damage during ischemic stroke. Earlier studies have characterized a neuroprotective role of the two-pore domain potassium channels KCNK2 (TREK1) and KCNK3 (TASK1). Protective neuronal hyperpolarization and prevention of intracellular Ca(2+) overload and glutamate excitotoxicity were suggested to be the underlying mechanisms. We here identify an unexpected role for the related KCNK5 channel in a mouse model of transient middle cerebral artery occlusion (tMCAO). KCNK5 is strongly upregulated on neurons upon cerebral ischemia, w...
Source: Pflugers Archiv : European Journal of Physiology - October 15, 2014 Category: Physiology Authors: Göb E, Bittner S, Bobak N, Kraft P, Göbel K, Langhauser F, Homola GA, Brede M, Budde T, Meuth SG, Kleinschnitz C Tags: Pflugers Arch Source Type: research

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