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ClC-3 induction protects against cerebral ischemia/reperfusion injury through promoting Beclin1/Vps34-mediated autophagy
AbstractAcute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was criti...
Source: Human Cell - August 8, 2020 Category: Cytology Source Type: research

Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke.
Abstract Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing...
Source: Experimental Neurology - April 7, 2020 Category: Neurology Authors: Wang S, Chen K, Yu J, Wang X, Li Q, Lv F, Shen H, Pei L Tags: Exp Neurol Source Type: research

Knockdown of Arginyl-tRNA Synthetase Attenuates Ischemia-Induced Cerebral Cortex Injury in Rats After Middle Cerebral Artery Occlusion
AbstractSome researchers have previously shown that RNAi knockdown of arginyl-tRNA synthetase (ArgRS) before or after a hypoxic injury can rescue animals from death, based on the model organism,C. elegans. However, there has been no study on the application of arginyl-tRNA synthetase knockdown in treating mammalian ischemic stroke, and its potential mechanism and effect on ischemic brain damage are still unknown. Here, we focused on the Rars gene, which encodes an arginyl-tRNA synthetase, and examined the effects of Rars knockdown in a permanent middle cerebral artery occlusion model in rats. To achieve this aim, adult mal...
Source: Translational Stroke Research - March 26, 2020 Category: Neurology Source Type: research

Molecular profile of the rat peri-infarct region four days after stroke: Study with MANF.
In this study, we examine the molecular profile of the peri-infarct region on post-stroke day four, time when reparative processes are ongoing. We used a multiomics approach, involving RNA sequencing, and mass spectrometry-based proteomics and metabolomics to characterize molecular changes in the peri-infarct region. We also took advantage of our previously developed method to express transgenes in the peri-infarct region where self-complementary adeno-associated virus (AAV) vectors were injected into the brain parenchyma on post-stroke day 2. We have previously used this method to show that mesencephalic astrocyte-derived...
Source: Experimental Neurology - March 26, 2020 Category: Neurology Authors: Teppo J, Vaikkinen A, Stratoulias V, Mätlik K, Anttila JE, Smolander OP, Pöhö P, Harvey BK, Kostiainen R, Airavaara M Tags: Exp Neurol Source Type: research

HIF ‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model.
HIF‑1α attenuates neuronal apoptosis by upregulating EPO expression following cerebral ischemia‑reperfusion injury in a rat MCAO model. Int J Mol Med. 2020 Jan 28;: Authors: Li J, Tao T, Xu J, Liu Z, Zou Z, Jin M Abstract Hypoxia‑inducible factor‑1α (HIF‑1α) is a key transcriptional factor in response to hypoxia and is involved in ischemic stroke. In the present study, the potential for HIF‑1α to inhibit neuronal apoptosis through upregulating erythropoietin (EPO) was investigated in a transient middle cerebral artery occlusion (tMCAO) rat stroke model. For this purpose, a recombinant ...
Source: International Journal of Molecular Medicine - January 27, 2020 Category: Molecular Biology Authors: Li J, Tao T, Xu J, Liu Z, Zou Z, Jin M Tags: Int J Mol Med Source Type: research

MST4 modulates the neuro-inflammatory response by regulating I κBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice.
MST4 modulates the neuro-inflammatory response by regulating IκBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice. Brain Res Bull. 2019 Nov 10;: Authors: Luan D, Zhang Y, Yuan L, Chu Z, Ma L, Xu Y, Zhao S Abstract MST4 limits peripheral, macrophage-dependent inflammatory responses through direct phosphorylation of the adaptor TRAF6; though its role in neuro-inflammation is unclear. We investigated microglia expression of MST4 and whether is attenuates neuro-inflammatory response after cerebral ischemia-reperfusion injury in mice. Adult male C57BL6 mice were su...
Source: Brain Research Bulletin - November 9, 2019 Category: Neurology Authors: Luan D, Zhang Y, Yuan L, Chu Z, Ma L, Xu Y, Zhao S Tags: Brain Res Bull Source Type: research

LRG1 Promotes Apoptosis and Autophagy through the TGFβ-smad1/5 Signaling Pathway to Exacerbate Ischemia/Reperfusion Injury
In this study, we discussed the function and mechanism of LRG1 in acute ischemic stroke from both basic and clinical research points of view. Mice underwent transient middle cerebral artery occlusion (tMCAO) surgery two weeks after LRG1 was overexpressed by the delivery of adeno-associated virus (AAV). For wild-type mice, both the protein and the transcript of LRG1 in the brain tissue were elevated after tMCAO. Meanwhile, the serum levels of LRG1 were decreased after tMCAO. The neuronal injury was shown aggravated in the AAV-LRG1 group (AAV-LRG1 mice with tMCAO) through infarction volume, neurological score, HE, and Nissl ...
Source: Neuroscience - June 18, 2019 Category: Neuroscience Source Type: research

OCT4B-190 protects against ischemic stroke by modulating GSK-3 β/HDAC6.
OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6. Exp Neurol. 2019 Apr 11;: Authors: Chen Y, Wu Z, Zhu X, Zhang M, Zang X, Li X, Xu Y Abstract OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase...
Source: Experimental Neurology - April 10, 2019 Category: Neurology Authors: Chen Y, Wu Z, Zhu X, Zhang M, Zang X, Li X, Xu Y Tags: Exp Neurol Source Type: research

TRIM9-Mediated Resolution of Neuroinflammation Confers Neuroprotection upon Ischemic Stroke in Mice
Publication date: 9 April 2019Source: Cell Reports, Volume 27, Issue 2Author(s): Jianxiong Zeng, Yaoming Wang, Zhifei Luo, Lin-Chun Chang, Ji Seung Yoo, Huan Yan, Younho Choi, Xiaochun Xie, Benjamin E. Deverman, Viviana Gradinaru, Stephanie L. Gupton, Berislav V. Zlokovic, Zhen Zhao, Jae U. JungSummaryExcessive and unresolved neuroinflammation is a key component of the pathological cascade in brain injuries such as ischemic stroke. Here, we report that TRIM9, a brain-specific tripartite motif (TRIM) protein, was highly expressed in the peri-infarct areas shortly after ischemic insults in mice, but expression was decreased ...
Source: Cell Reports - April 10, 2019 Category: Cytology Source Type: research

MST1 Suppression Reduces Early Brain Injury by Inhibiting the NF- κB/MMP-9 Pathway after Subarachnoid Hemorrhage in Mice.
Conclusions: The current findings indicate that MST1 participates in SAH-induced BBB disruption and white matter fiber damage via the downstream NF-κB-MMP-9 signaling pathway. Therefore, MST1 antagonists may serve as a novel therapeutic target to prevent early brain injury in SAH patients. PMID: 30018671 [PubMed - in process]
Source: Behavioural Neurology - July 20, 2018 Category: Neurology Authors: Qu J, Zhao H, Li Q, Pan P, Ma K, Liu X, Feng H, Chen Y Tags: Behav Neurol Source Type: research

Neuroscience is the Next Oncology
by Michael D. Ehlers, MD, PhD Dr. Ehlers is with Biogen in Cambridge, Massachusetts. Innov Clin Neurosci. 2018;15(3–4):15–16 Funding: No funding was received for the preparation of this article. Disclosures: Dr. Ehlers is an employee and shareholder at Biogen Inc. in Cambridge, Massachusetts. Prominent and expensive failures in Alzheimer’s disease therapies have led to a contagious belief system in some parts of the biopharma industry that neuroscience is just too hard, too risky, and too uncertain. But, might this belief system itself be a residual bias of the past? Close inspection reveals all the signs of a coming...
Source: Innovations in Clinical Neuroscience - April 1, 2018 Category: Neuroscience Authors: ICNS Online Editor Tags: Commentary Current Issue Source Type: research

Adenoviruses-mediated RNA interference targeting cytosolic phospholipase A2 α attenuates focal ischemic brain damage in mice.
Adenoviruses-mediated RNA interference targeting cytosolic phospholipase A2α attenuates focal ischemic brain damage in mice. Mol Med Rep. 2018 Feb 15;: Authors: Wu H, Liu H, Zuo F, Zhang L Abstract Cerebral ischemia injury is a clinical, frequently occurring disease, which causes a heavy burden on society and families. It has been demonstrated that cytosolic phospholipase A2α (cPLA2α) is significant in neurological injury caused by ischemic brain injury, and inhibition of cPLA2α may reduce stroke injury. In the present study, the role of cPLA2α was investigated in a mouse model of middle cerebral...
Source: Molecular Medicine Reports - February 28, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke Brief Report
Conclusions—Using MassTag–polymerase chain reaction, we detected parvovirus B19—a virus known to infect erythrocytes and endothelial cells—in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.
Source: Stroke - September 25, 2017 Category: Neurology Authors: Heather J. Fullerton, Jorge M. Luna, Max Wintermark, Nancy K. Hills, Rafal Tokarz, Ying Li, Carol Glaser, Gabrielle A. DeVeber, W. Ian Lipkin, Mitchell S.V. Elkind Tags: Pediatrics, Ischemic Stroke Brief Reports Source Type: research

ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery
Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)–cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) break...
Source: Blood - July 6, 2017 Category: Hematology Authors: Xu, H., Cao, Y., Yang, X., Cai, P., Kang, L., Zhu, X., Luo, H., Lu, L., Wei, L., Bai, X., Zhu, Y., Zhao, B.-Q., Fan, W. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research

A BAG3 Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.
Conclusions -Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle function in the setting of ischemia. PMID: 28442482 [PubMed - as supplied by publisher]
Source: Circulation - April 25, 2017 Category: Cardiology Authors: McClung JM, McCord TJ, Ryan TE, Schmidt CA, Green TD, Southerland KW, Reinardy JL, Mueller SB, Venkatraman TN, Lascola CD, Keum S, Marchuk DA, Spangenburg EE, Dokun AO, Annex BH, Kontos CD Tags: Circulation Source Type: research

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