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neurovascular unit* AND cerebral ischemia

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https://www.readbyqxmd.com/read/30308244/endothelial-cells-promote-excitatory-synaptogenesis-and-improve-ischemia-induced-motor-deficits-in-neonatal-mice
#1
Kun-Wei Wu, Ling-Ling Lv, Yu Lei, Cheng Qian, Feng-Yan Sun
Brain microvascular endothelial cells (BMEC) are highly complex regulatory cells that communicate with other cells in the neurovascular unit. Cerebral ischemic injury is known to produce detectable synaptic dysfunction. This study aims to investigate whether endothelial cells in the brain regulate postnatal synaptic development and to elucidate their role in functional recovery after ischemia. Here, we found that in vivo engraftment of endothelial cells increased synaptic puncta and excitatory postsynaptic currents in layers 2/3 of the motor cortex...
October 8, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/30214637/ampk-potential-therapeutic-target-for-ischemic-stroke
#2
REVIEW
Shuai Jiang, Tian Li, Ting Ji, Wei Yi, Zhi Yang, Simeng Wang, Yang Yang, Chunhu Gu
5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine (Ser/Thr) kinase group, is universally distributed in various cells and organs. It is a significant endogenous defensive molecule that responds to harmful stimuli, such as cerebral ischemia, cerebral hemorrhage, and, neurodegenerative diseases (NDD). Cerebral ischemia, which results from insufficient blood flow or the blockage of blood vessels, is a major cause of ischemic stroke. Ischemic stroke has received increased attention due to its '3H' effects, namely high mortality, high morbidity, and high disability...
2018: Theranostics
https://www.readbyqxmd.com/read/30147301/profile-of-intravenous-glyburide-for-the-prevention-of-cerebral-edema-following-large-hemispheric-infarction-evidence-to-date
#3
REVIEW
Zachary A King, Kevin N Sheth, W Taylor Kimberly, J Marc Simard
Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29964088/mitophagy-is-activated-in-brain-damage-induced-by-cerebral-ischemia-and-reperfusion-via-the-pink1-parkin-p62-signalling-pathway
#4
Rui Lan, Ji-Tao Wu, Tao Wu, Yun-Zhi Ma, Bao-Qi Wang, Hai-Zhong Zheng, Ya-Na Li, Yan Wang, Chun-Qing Gu, Yong Zhang
This study examined the course of mitophagy following cerebral ischemia with reperfusion and the role of the PTEN-induced kinase 1 (PINK1)/Parkin/p62 signalling pathway. The middle cerebral artery of male Sprague-Dawley rats was occluded for 90 min and was followed by different time-points of reperfusion. Cerebral infarct areas were detected by 2,3,5-triphenyl tetrazolium chloride staining, while brain damage was observed by haematoxylin and eosin staining. Levels of LC3, Beclin1 and LAMP-1 were estimated by western blots...
September 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29933207/multi-targeting-effects-of-a-new-synthetic-molecule-jm-20-in-experimental-models-of-cerebral-ischemia
#5
REVIEW
Yanier Nuñez-Figueredo, Jeney Ramírez-Sánchez, Gilberto L Pardo Andreu, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, Diogo O Souza
Ischemic stroke is a major cause of death and disability worldwide. Thrombolysis by tissue plasminogen activator is the only pharmacological treatment approved for clinical practice, but has a narrow therapeutic window and poor efficacy when the cell death cascade is activated. Numerous drugs that are thought to protect neurons against injury have previously failed in human trials despite showing efficacy in experimental models of stroke. Herein, we reviewed the main pre-clinical results of the neuroprotective effects of JM-20, a new hybrid molecule, against brain ischemia...
August 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29763986/early-iv-injected-human-dermis-derived-mesenchymal-stem-cells-after-transient-global-cerebral-ischemia-do-not-pass-through-damaged-blood-brain-barrier
#6
Ji Hyeon Ahn, Bai Hui Chen, Joon Ha Park, Bich Na Shin, Tae-Kyeong Lee, Jeong Hwi Cho, Jae Chul Lee, Jeong-Ran Park, Se-Ran Yang, Sungwoo Ryoo, Myoung Cheol Shin, Jun Hwi Cho, Il Jun Kang, Choong Hyun Lee, In Koo Hwang, Young-Myeong Kim, Moo-Ho Won
There is lack of researches on effects of intravenously injected mesenchymal stem cells (MSCs) against transient cerebral ischemia (TCI). We investigated the disruption of the neurovascular unit (NVU), which comprises the blood-brain barrier and examined entry of human dermis-derived MSCs (hDMSCs) into the damaged hippocampal CA1 area in a gerbil model of TCI and their subsequent effects on neuroprotection and cognitive function. Impairments of neurons and blood-brain barrier were examined by immunohistochemistry, electron microscopy, and Evans blue and immunoglobulin G leakage...
July 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29762759/measuring-the-impact-of-delayed-cerebral-ischemia-on-neuropsychological-outcome-after-aneurysmal-subarachnoid-hemorrhage-protocol-of-a-swiss-nationwide-observational-study-moca-dci-study
#7
Martin N Stienen, Christian Fung, Philippe Bijlenga, Daniel W Zumofen, Rodolfo Maduri, Thomas Robert, Martin A Seule, Serge Marbacher, Olivia Geisseler, Peter Brugger, Klemens Gutbrod, Christian Chicherio, Andreas U Monsch, Valérie Beaud, Stefania Rossi, Severin Früh, Nicole Schmid, Nicolas R Smoll, Emanuela Keller, Luca Regli
BACKGROUND: The exact relationship between delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and neuropsychological impairment remains unknown, as previous studies lacked a baseline examination after aneurysm occlusion but before the DCI-period. Neuropsychological evaluation of acutely ill patients is often applied in a busy intensive care unit (ICU), where distraction represents a bias to the obtained results. OBJECTIVE: To evaluate the relationship between DCI and neuropsychological outcome after aSAH by comparing the Montreal Cognitive Assessment (MoCA) results in aSAH patients with and without DCI at 3 mo with a baseline examination before the DCI-period (part 1)...
May 11, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29570780/effects-of-ischemic-post-conditioning-on-neuronal-vegf-regulation-and-microglial-polarization-in-a-rat-model-of-focal-cerebral-ischemia
#8
Elga Esposito, Kazuhide Hayakawa, Bum Ju Ahn, Su Jing Chan, Changhong Xing, Anna C Liang, Kyu-Won Kim, Ken Arai, Eng H Lo
Ischemic postconditioning is increasingly being investigated as a therapeutic approach for cerebral ischemia. However, the majority of studies are focused on the acute protection of neurons per se. Whether and how postconditioning affects multiple cells in the recovering neurovascular unit remains to be fully elucidated. Here, we asked whether postconditioning may modulate help-me signaling between injured neurons and reactive microglia. Rats were subjected to 100 min of focal cerebral ischemia, then randomized into a control versus postconditioning group...
July 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29564811/recovery-of-neurovascular-unit-integrity-by-cdk5-kd-astrocyte-transplantation-in-a-global-cerebral-ischemia-model
#9
Andrea Becerra-Calixto, Rafael Posada-Duque, Gloria Patricia Cardona-Gómez
Astrocytes play metabolic and structural support roles and contribute to the integrity of the blood-brain barrier (BBB), linking communication between neurons and the endothelium. Cyclin-dependent kinase 5 (CDK5) likely exerts a dual effect on the endothelium and astrocytes due to its involvement in migration and angiogenesis; the overactivation of CDK5 is associated with dysfunction in glutamate recapture and hypoxia. Recently, we proposed that CDK5-targeted astrocytes facilitate the recovery of neurological and motor function in transplanted ischemic rats...
November 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29499167/salubrinal-and-robenacoxib-treatment-after-global-cerebral-ischemia-exploring-the-interactions-between-er-stress-and-inflammation
#10
Berta Anuncibay-Soto, Diego Pérez-Rodriguez, María Santos-Galdiano, Enrique Font-Belmonte, Irene F Ugidos, Paloma Gonzalez-Rodriguez, Marta Regueiro-Purriños, Arsenio Fernández-López
BACKGROUND: Blood reperfusion of the ischemic tissue after stroke promotes increases in the inflammatory response as well as accumulation of unfolded/misfolded proteins in the cell, leading to endoplasmic reticulum (ER) stress. Both Inflammation and ER stress are critical processes in the delayed death of the cells damaged after ischemia. The aim of this study is to check the putative synergic neuroprotective effect by combining anti-inflammatory and anti-ER stress agents after ischemia...
May 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29467621/immunosignals-of-oligodendrocyte-markers-and-myelin-associated-proteins-are-critically-affected-after-experimental-stroke-in-wild-type-and-alzheimer-modeling-mice-of-different-ages
#11
Dominik Michalski, Anna L Keck, Jens Grosche, Henrik Martens, Wolfgang Härtig
Because stroke therapies are still limited and patients are often concerned by long-term sequelae with significant impairment of daily living, elaborated neuroprotective strategies are needed. During the last decades, research substantially improved the knowledge on cellular pathologies responsible for stroke-related tissue damage. In this context, the neurovascular unit (NVU) concept has been established, summarizing the affections of neurons, associated astrocytes and the vasculature. Although oligodendrocytes were already identified to play a major role in other brain pathologies, their role during stroke evolution and long-lasting tissue damage is poorly understood...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29445328/hippocampal-atrophy-following-subarachnoid-hemorrhage-correlates-with-disruption-of-astrocyte-morphology-and-capillary-coverage-by-aqp4
#12
Maryam Anzabi, Maryam Ardalan, Nina K Iversen, Ali H Rafati, Brian Hansen, Leif Østergaard
Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29398538/2-2-benzofuranyl-2-imidazoline-mediates-neuroprotection-by-regulating-the-neurovascular-unit-integrity-in-a-rat-model-of-focal-cerebral-ischemia
#13
Zheng Zhang, Linlei Zhang, Jiaou Chen, Yungang Cao, Man Qu, Xinda Lin, Zhao Han, Xunming Ji
BACKGROUND: We showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia. METHODS: Rats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO)...
June 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29323038/electroacupuncture-improves-neurovascular-unit-reconstruction-by-promoting-collateral-circulation-and-angiogenesis
#14
Lei Shi, Hong-Mei Cao, Ying Li, Shi-Xin Xu, Yan Zhang, Yang Zhang, Zhe-Feng Jin
Acupuncture at Shuigou (GV26) shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26 (15 Hz and 1 mA, continuous wave [biphasic pulses], for 5 minutes). Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29180303/effects-of-erythropoietin-on-astrocytes-and-brain-endothelial-cells-in-primary-culture-during-anoxia-depend-on-simultaneous-signaling-by-other-cytokines-and-on-duration-of-anoxia
#15
Hameed Al-Sarraf, Slava Malatiali, Mariam Al-Awadi, Zoran Redzic
Studies on animals revealed neuroprotective effects of exogenously applied erythropoietin (EPO) during cerebral ischemia/hypoxia. Yet, application of exogenous EPO in stroke patients often lead to haemorrhagic transformation. To clarify potential mechanism of this adverse effect we explored effects of EPO on viabilities of astrocytes and brain endothelial cells (BECs) in primary culture during anoxia of various durations, in the presence or absence of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1), which are cytokines that are also released from the neurovascular unit during hypoxia...
February 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29133510/single-cell-immuno-laser-microdissection-coupled-to-label-free-proteomics-to-reveal-the-proteotypes-of-human-brain-cells-after-ischemia
#16
Teresa García-Berrocoso, Víctor Llombart, Laura Colàs-Campàs, Alexandre Hainard, Virginie Licker, Anna Penalba, Laura Ramiro, Alba Simats, Alejandro Bustamante, Elena Martínez-Saez, Francesc Canals, Jean-Charles Sanchez, Joan Montaner
Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes. In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas...
January 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-repair-the-genome-and-improve-stroke-recovery
#17
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29034608/nanoparticle-based-therapeutics-for-brain-injury
#18
REVIEW
Vimala N Bharadwaj, Duong T Nguyen, Vikram D Kodibagkar, Sarah E Stabenfeldt
Brain injuries affect a large patient population with major physical and emotional suffering for patients and their relatives; at a significant cost to the society. Effective diagnostic and therapeutic options available for brain injuries are limited by the complex brain injury pathology involving blood-brain barrier (BBB). Brain injuries, including ischemic stroke and brain trauma, initiate BBB opening for a short period of time, which is followed by a second reopening for an extended time. The leaky BBB and/or the alterations in the receptor expression on BBB may provide opportunities for therapeutic delivery via nanoparticles (NPs)...
January 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28959727/elovanoids-are-a-novel-class-of-homeostatic-lipid-mediators-that-protect-neural-cell-integrity-upon-injury
#19
Surjyadipta Bhattacharjee, Bokkyoo Jun, Ludmila Belayev, Jessica Heap, Marie-Audrey Kautzmann, Andre Obenaus, Hemant Menghani, Shawn J Marcell, Larissa Khoutorova, Rong Yang, Nicos A Petasis, Nicolas G Bazan
We report the characterization of a novel class of lipid mediators termed elovanoids (ELVs) (ELV-N32 and ELV-N34), which are dihydroxylated derivatives of 32:6n3 and 34:6n3, respectively. The precursors of ELVs are made by elongation of a 22:6n3 fatty acid and catalyzed by ELOVL4 (elongation of very-long-chain fatty acids-4). The structure and stereochemistry of ELVs were established using synthetic compounds produced by stereocontrolled total synthesis. We report that ELV-mediated protection is induced in neuronal cultures undergoing either oxygen/glucose deprivation or N-methyl-d-aspartate receptor-mediated excitotoxicity, as well as in experimental ischemic stroke...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28860977/damaged-neocortical-perineuronal-nets-due-to-experimental-focal-cerebral-ischemia-in-mice-rats-and-sheep
#20
Wolfgang Härtig, Bianca Mages, Susanne Aleithe, Björn Nitzsche, Stephan Altmann, Henryk Barthel, Martin Krueger, Dominik Michalski
As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU), their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept...
2017: Frontiers in Integrative Neuroscience
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