scholarly journals Dysregulation of Astrocyte Ion Homeostasis and Its Relevance for Stroke-Induced Brain Damage

2021 ◽  
Vol 22 (11) ◽  
pp. 5679
Author(s):  
Michel J. A. M. van Putten ◽  
Christoph Fahlke ◽  
Karl W. Kafitz ◽  
Jeannette Hofmeijer ◽  
Christine R. Rose
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Cerebral Edema ◽  
Ion Homeostasis ◽  
Energy Depletion ◽  
Brain Functioning ◽  
Tripartite Synapse ◽  
Chronic Disability ◽  
Cellular Volume ◽  
Monovalent Ions

Ischemic stroke is a leading cause of mortality and chronic disability. Either recovery or progression towards irreversible failure of neurons and astrocytes occurs within minutes to days, depending on remaining perfusion levels. Initial damage arises from energy depletion resulting in a failure to maintain homeostasis and ion gradients between extra- and intracellular spaces. Astrocytes play a key role in these processes and are thus central players in the dynamics towards recovery or progression of stroke-induced brain damage. Here, we present a synopsis of the pivotal functions of astrocytes at the tripartite synapse, which form the basis of physiological brain functioning. We summarize the evidence of astrocytic failure and its consequences under ischemic conditions. Special emphasis is put on the homeostasis and stroke-induced dysregulation of the major monovalent ions, namely Na+, K+, H+, and Cl-, and their involvement in maintenance of cellular volume and generation of cerebral edema.

scholarly journals Effect of glibenclamide on the prevention of secondary brain injury following ischemic stroke in humans

2014 ◽  
Vol 36 (1) ◽  
pp. E11 ◽  
Author(s):  
Arjun Khanna ◽  
Brian P. Walcott ◽  
Kristopher T. Kahle ◽  
J. Marc Simard
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Edema ◽  
Vasogenic Edema ◽  
Ion Homeostasis ◽  
Secondary Brain Injury ◽  
Protective Effects ◽  
Cation Conductance ◽  
Integral Role ◽  
Prospective Phase ◽  
Molecular Pathophysiology

Cerebral edema and hemorrhagic conversion are common, potentially devastating complications of ischemic stroke and are associated with high rates of mortality and poor functional outcomes. Recent work exploring the molecular pathophysiology of the neurogliovascular unit in ischemic stroke suggests that deranged cellular ion homeostasis due to altered function and regulation of ion pumps, channels, and secondary active transporters plays an integral role in the development of cytotoxic and vasogenic edema and hemorrhagic conversion. Among these proteins involved in ion homeostasis, the ischemia-induced, nonselective cation conductance formed by the SUR1-TRPM4 protein complex appears to play a prominent role and is potently inhibited by glibenclamide, an FDA-approved drug commonly used in patients with Type 2 diabetes. Several robust preclinical studies have demonstrated the efficacy of glibenclamide blockade of SUR1-TRPM4 activity in reducing edema and hemorrhagic conversion in rodent models of ischemic stroke, prompting the study of the potential protective effects of glibenclamide in humans in an ongoing prospective phase II clinical trial. Preliminary data suggest glibenclamide significantly reduces cerebral edema and lowers the rate of hemorrhagic conversion following ischemic stroke, suggesting the potential use of glibenclamide to improve outcomes in humans.

scholarly journals Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Rabbit Model ◽  
Specific Area ◽  
Brain Atlas ◽  
Rabbit Brain ◽  
Stroke Model ◽  
Triphenyltetrazolium Chloride ◽  
Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

scholarly journals Physiological and Pathological Ageing of Astrocytes in the Human Brain

2021 ◽  
Author(s):  
Marloes Verkerke ◽  
Elly M. Hol ◽  
Jinte Middeldorp
Keyword(s):  
Risk Factor ◽  
Morphological Changes ◽  
Ion Homeostasis ◽  
Brain Functioning ◽  
Physiological Ageing ◽  
Human Astrocytes ◽  
Age Related ◽  
Technical Issues ◽  
Neuronal Transmission ◽  
Ageing Brain

AbstractAgeing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE ε4 is genetically the strongest risk factor for Alzheimer’s disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain.

scholarly journals Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection

Aging Cell ◽  
2013 ◽  
Vol 12 (5) ◽  
pp. 842-850 ◽  
Author(s):  
Hiramani Dhungana ◽  
Tarja Malm ◽  
Adam Denes ◽  
Piia Valonen ◽  
Sara Wojciechowski ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Peripheral Infection

scholarly journals Early administration of MPC-n(IVIg) selectively accumulates in ischemic areas to protect inflammation-induced brain damage from ischemic stroke

Theranostics ◽  
2021 ◽  
Vol 11 (17) ◽  
pp. 8197-8217
Author(s):  
Weili Jin ◽  
Ye Wu ◽  
Ning Chen ◽  
Qixue Wang ◽  
Yunfei Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Early Administration

scholarly journals Cation-chloride cotransporters, Na/K pump, and channels in cell water and ions regulation: in silico and experimental studies of the U937 cells under stopping the pump and during RVD

2021 ◽  
Author(s):  
Alexey A Vereninov ◽  
Valentina Yurinskaya
Keyword(s):  
Plasma Membrane ◽  
Cell Membrane ◽  
Real Time ◽  
Intracellular Signaling ◽  
Ion Homeostasis ◽  
Regulatory Volume Decrease ◽  
Experimental Studies ◽  
U937 Cells ◽  
Ionic Homeostasis ◽  
Monovalent Ions

Cation-coupled chloride cotransporters play a key role in generating the Cl− electrochemical gradient on the cell membrane which is important for regulation of many cellular processes. However, the cooperation of transporters and channels of the plasma membrane in holding the ionic homeostasis of the whole cell remains poorly characterized because of the lack of a suitable tool for its computation. Our software successfully predicted in real-time changes in the ion homeostasis of U937 cells after stopping the Na/K pump, but so far considered the model with only NC cotransporter. Here the model with all main types of cotransporters is used in computation of the rearrangements of ionic homeostasis due to stopping the pump and associated with the regulatory volume decrease (RVD) of cells swollen in hypoosmolar medium. The parameters obtained for the real U937 cells are used. Successful prediction of changes in ion homeostasis in real-time after stopping the pump using the model with all major cotransporters indicates that the model is reliable. Using this model for analysis RVD showed that there is a "physical" RVD, associated with the time-dependent changes in electrochemical ion gradients, but not with alteration of channels and transporters of the plasma membrane that should be considered in studies of truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the partial unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.

scholarly journals Urokinase-type plasminogen activator (uPA) protects the tripartite synapse in the ischemic brain via ezrin-mediated formation of peripheral astrocytic processes

2018 ◽  
Vol 39 (11) ◽  
pp. 2157-2171 ◽  
Author(s):  
Ariel Diaz ◽  
Paola Merino ◽  
Luis G Manrique ◽  
Lihong Cheng ◽  
Manuel Yepes
Keyword(s):  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Harmful Effect ◽  
Ischemic Injury ◽  
Adult Brain ◽  
Subsequent Formation ◽  
Ischemic Brain ◽  
Tripartite Synapse ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Cerebral ischemia has a harmful effect on the synapse associated with neurological impairment. The “tripartite synapse” is assembled by the pre- and postsynaptic terminals, embraced by astrocytic elongations known as peripheral astrocytic processes (PAPs). Ischemic stroke induces the detachment of PAPs from the synapse, leading to synaptic dysfunction and neuronal death. Ezrin is a membrane-associated protein, required for the formation of PAPs, that links the cell surface to the actin cytoskeleton. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to its receptor (uPAR) promotes neurite growth during development. In the adult brain, neurons release uPA and astrocytes recruit uPAR to the plasma membrane during the recovery phase from an ischemic stroke, and uPA/uPAR binding promotes functional improvement following an ischemic injury. We found that uPA induces the synthesis of ezrin in astrocytes, with the subsequent formation of PAPs that enter in direct contact with the synapse. Furthermore, either the release of neuronal uPA or intravenous treatment with recombinant uPA (ruPA) induces the formation of PAPs in the ischemic brain, and the interaction of these PAPs with the pre- and postsynaptic terminals protects the integrity of the “tripartite synapse” from the harmful effects of the ischemic injury.

Abstract T P45: Automated CSF Segmentation to Quantify Cerebral Edema Following Large Hemispheric Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Yasheng Chen ◽  
Qingyang Yuan ◽  
Raj Dhar ◽  
Kristin Guilliams ◽  
Laura Heitsch ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Edema ◽  
Large Population ◽  
False Negative ◽  
Hounsfield Unit ◽  
Ground Truth ◽  
Mass Effect ◽  
Stroke Patients ◽  
Segmentation Strategy ◽  
Combined Strategy

Introduction: Cerebral edema with resultant mass effect is a potentially fatal consequence of ischemic stroke, but early and sensitive biomarkers of brain tissue compression are lacking. To quantify brain mass effect, we developed a novel, automated segmentation method to delineate CSF spaces in CT images from ischemic stroke patients. Methods: CTs from sixteen acute ischemic stroke patients (median NIHSS 16.5, median age 61.5 yrs, 14-92 hrs after stroke onset) were included after informed consent was obtained. After infarction, conventional CSF segmentation using Hounsfield unit (HU) thresholding is suboptimal due to infarct hypodensity. Utilizing manually delineated infarct and CSF spaces as training samples, we augmented conventional HU threshold segmentation with level sets, sparse regression and random forest segmentation methods. Using leave-one-out cross-validation, the combined approach was compared to HU thresholding using Dice ratios (a measure of the overlap between the segmented and the ground-truth CSF spaces). Results: Shown is an example of a CT brain slice segmented by HU thresholding and the combined strategy: false negative (red), false positive (green), and true positive (yellow). The Dice ratios for HU thresholding and the combined approaches were 58.2±16.3% and 68.9±14.6%, respectively, demonstrating the significantly improved performance for the combined strategy (p=0.0014). Conclusions: We have developed an advanced image segmentation strategy to delineate CSF spaces which outperforms conventional HU thresholding. An automated CSF segmentation strategy will permit quantification of cerebral edema in a large population of stroke patients, as required for genetic studies, for example.

Abstract P198: WNK-SPAK-NKCC1 Cascade Activation Contributes to Worsened Brain Damage in Mice With Hypertension Co-Morbidity after Ischemic Stroke

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Mohammad Iqbal H Bhuiyan ◽  
Huachen Huang ◽  
Ting Zhang ◽  
Bradley J Molyneaux ◽  
Samuel M Poloyac ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Co Morbidity
Sign in / Sign up

Export Citation Format

Share Document