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Stroke neuroprotective

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https://www.readbyqxmd.com/read/29775963/brain-ischemic-preconditioning-protects-against-ischemic-injury-and-preserves-the-blood-brain-barrier-via-oxidative-signaling-and-nrf2-activation
#1
Tuo Yang, Yang Sun, Leilei Mao, Meijuan Zhang, Qianqian Li, Lili Zhang, Yejie Shi, Rehana K Leak, Jun Chen, Feng Zhang
Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199)...
May 6, 2018: Redox Biology
https://www.readbyqxmd.com/read/29774054/beta-adrenoceptor-blockade-ameliorates-impaired-glucose-tolerance-and-alterations-of-the-cerebral-ceramide-metabolism-in-an-experimental-model-of-ischemic-stroke
#2
Sebastian Luger, Annette Schwebler, Rajkumar Vutukuri, Nerea Ferreiros Bouzas, Sandra Labocha, Yannick Schreiber, Robert Brunkhorst, Helmuth Steinmetz, Josef Pfeilschifter, Waltraud Pfeilschifter
Background: Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis and are involved in cellular stress responses. Experimental evidence suggests a pivotal role of sphingolipids in the pathogenesis of cardiovascular diseases, including ischemic stroke. A neuroprotective effect has been shown for beta-adrenergic antagonists in rodent stroke models and supported by observational clinical data...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29772377/impact-of-steroid-hormones-e2-and-p-on-the-nlrp3-asc-casp1-axis-in-primary-mouse-astroglia-and-bv-2-cells-after-in-vitro-hypoxia
#3
Alexander Slowik, Leoni Lammerding, Adib Zendedel, Pardes Habib, Cordian Beyer
Clinical and animal model studies have demonstrated the neuroprotective and anti-inflammatory effects of 17beta-estradiol (E2) and progesterone (P) in different disease models of the central nervous system (CNS) including ischemic stroke. Inflammasomes are involved in the interleukin-1 beta (IL1beta) maturation, in particular, NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the active caspase-1 (Casp1) form. Recently, we showed that administration of E2 or P selectively regulated these components after experimental ischemic stroke in rats...
May 14, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29770166/free-radical-damage-in-ischemia-reperfusion-injury-an-obstacle-in-acute-ischemic-stroke-after-revascularization-therapy
#4
REVIEW
Ming-Shuo Sun, Hang Jin, Xin Sun, Shuo Huang, Fu-Liang Zhang, Zhen-Ni Guo, Yi Yang
Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29769639/a-novel-cell-penetrating-peptide-protects-against-neuron-apoptosis-after-cerebral-ischemia-by-inhibiting-the-nuclear-translocation-of-annexin-a1
#5
Xing Li, Lu Zheng, Qian Xia, Lu Liu, Meng Mao, Huijuan Zhou, Yin Zhao, Jing Shi
Nuclear translocation of annexin A1 (ANXA1) has recently been reported to participate in neuronal apoptosis after cerebral ischemia. Prevention of the nuclear translocation of ANXA1 should therefore inhibit neuronal apoptosis and protect against cerebral stroke. Here, we found that, in the repeat III domain of ANXA1, the amino-acid residues from R228 to F237 function as a unique nuclear translocation signal (NTS) and are required for nuclear translocation of ANXA1. Intriguingly, we synthesized a cell-penetrating peptide derived by conjugating the trans-activator of transcription (Tat) domain to the NTS sequence...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29766811/p2x7-receptor-associated-programmed-cell-death-in-the-pathophysiology-of-hemorrhagic-stroke
#6
Hengli Zhao, Yujie Chen, Hua Feng
Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of cerebral blood vessels, and cell death is widely believed to occur after exposure to blood metabolites or subsequently damaged cells. Recently, programmed cell death, such as apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, has been demonstrated to play crucial roles in the pathophysiology of stroke. However, the detailed mechanisms of these novel kinds of cell death are still unclear. The P2X7 receptor, previously known for its cytotoxic activity, is an ATP-gated, non-selective cation channel that belongs to the family of ionotropic P2X receptors...
May 15, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29766794/chitosan-coated-c-phycocyanin-liposome-for-extending-the-neuroprotective-time-window-against-ischemic-brain-stroke
#7
Goo Yong Chung, Kyou Hee Shim, Hye Jin Kim, Seul Ki Min, Hwa Sung Shin
The time window for neuroprotection during ischemic brain stroke is short, and hence, development of neuroprotectants is a critical to extend this time window. This study sought to verify if muco-adhesive chitosan coating improves the neuroprotective potential of the pre-proven C-Phycocyanin-pertaining liposome (C-Pc liposome). The use of chitosan-coated liposomes extended the neuroprotective time window by 6 h after reperfusion, and further improved the neuroprotection efficiency of the C-Pc liposome in a rat middle cerebral artery occlusion (MCAO) model...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29765502/the-phenolic-components-of-gastrodia-elata-improve-prognosis-in-rats-after-cerebral-ischemia-reperfusion-by-enhancing-the-endogenous-antioxidant-mechanisms
#8
Anhuan Shi, Jianming Xiang, Fangyan He, Yanping Zhu, Gongbei Zhu, Yuhan Lin, Ningna Zhou
Pharmacological or spontaneous thrombolysis in ischemic stroke triggers an outbreak of reactive oxygen species and results in neuron death. Nrf2-mediated antioxidation in cells has been proved as a pivotal target for neuroprotection. This research reports that phenolic components of Gastrodia elata Blume (PCGE), a traditional Chinese medicine, can alleviate the pathological lesions in the penumbra and hippocampus by increasing the survival of neurons and astrocytes and improve neurofunction and cognition after reperfusion in a rat model of middle cerebral artery occlusion...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29765412/neural-stem-cell-conditioned-medium-ameliorated-cerebral-ischemia-reperfusion-injury-in-rats
#9
HongNa Yang, Cuilan Wang, Hui Chen, Lan Li, Shuang Ma, Hao Wang, YaRu Fu, Tingyu Qu
Introduction: Our previous study suggested that NSC-CM (neural stem cell-conditioned medium) inhibited cell apoptosis in vitro . In addition, many studies have shown that neurotrophic factors and microparticles secreted into a conditioned medium by NSCs had neuroprotective effects. Thus, we hypothesized that NSC-CM had the capacity of protecting against cerebral I/R injury. Methods: Adult male Sprague-Dawley rats receiving middle cerebral artery occlusion surgery as an animal model of cerebral I/R injury were randomly assigned to two groups: the control group and NSC-CM-treated group...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29764541/-tianjin-characteristics-of-integrated-traditional-chinese-and-western-medicine-in-first-aid-medical-system
#10
Zhijun Li
Tianjin, as the earliest city to open up, the exchange of Chinese and Western cultures also started earlier. Therefore, today's emergency medicine system with integrated features of Chinese and Western medicine is formed. Professor Wang Jinda, who works in Tianjin First Center Hospital, makes the theory of "treating bronchitis and treating diseases" and "three methods of three syndromes" for the treatment of severe diseases such as sepsis. The surgical aspect is the treatment of acute abdomen with the combination of Chinese and Western medicine which is proposed by Academician Wu Xianzhong who worked in Tianjin Nankai Hospital...
May 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29758244/neural-stem-cell-therapies-and-hypoxic-ischemic-brain-injury
#11
REVIEW
Lei Huang, Lubo Zhang
Hypoxic-ischemic brain injury is a significant cause of morbidity and mortality in the adult as well as in the neonate. Extensive pre-clinical studies have shown promising therapeutic effects of neural stem cell-based treatments for hypoxic-ischemic brain injury. There are two major strategies of neural stem cell-based therapies: transplanting exogenous neural stem cells and boosting self-repair of endogenous neural stem cells. Neural stem cell transplantation has been proved to improve functional recovery after brain injury through multiple by-stander mechanisms (e...
May 11, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29756681/neuronal-il-4r%C3%AE-modulates-neuronal-apoptosis-and-cell-viability-during-the-acute-phases-of-cerebral-ischemia
#12
Han Kyu Lee, Sehwon Koh, Donald C Lo, Douglas A Marchuk
Ischemic stroke caused by an embolus or local thrombosis results in neural tissue damage (an infarct) in the territory of the occluded cerebral artery. Decades of studies have increased our understanding of the molecular events during cerebral infarction; however, translation of these discoveries to druggable targets for ischemic stroke treatment has been largely disappointing. Interleukin-4 (IL-4) is a multifunctional cytokine that exerts its cellular activities via the interleukin-4 receptor α (IL-4Rα)...
May 14, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29756589/effect-of-combination-therapy-with-neuroprotective-and-vasoprotective-agents-on-cerebral-ischemia
#13
Jiping Yang, Bei Yang, Baoxin Xiu, Jinchong Qi, Huaijun Liu
Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits. METHODS: Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group...
May 2018: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/29743976/cell-type-specific-mechanisms-in-the-pathogenesis-of-ischemic-stroke-the-role-of-apoptosis-signal-regulating-kinase-1
#14
REVIEW
So Yeong Cheon, Eun Jung Kim, Jeong Min Kim, Bon-Nyeo Koo
Stroke has become a more common disease worldwide. Despite great efforts to develop treatment, little is known about ischemic stroke. Cerebral ischemia activates multiple cascades of cell type-specific pathomechanisms. Ischemic brain injury consists of a complex series of cellular reactions in various cell types within the central nervous system (CNS) including platelets, endothelial cells, astrocytes, neutrophils, microglia/macrophages, and neurons. Diverse cellular changes after ischemic injury are likely to induce cell death and tissue damage in the brain...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29742958/mitochondrial-zn-2-accumulation-a-potential-trigger-of-hippocampal-ischemic-injury
#15
Sung G Ji, Yuliya V Medvedeva, Hwai-Lee Wang, Hong Z Yin, John H Weiss
Ischemic stroke is a major cause of death and disabilities worldwide, and it has been long hoped that improved understanding of relevant injury mechanisms would yield targeted neuroprotective therapies. While Ca2+ overload during ischemia-induced glutamate excitotoxicity has been identified as a major contributor, failures of glutamate targeted therapies to achieve desired clinical efficacy have dampened early hopes for the development of new treatments. However, additional studies examining possible contributions of Zn2+ , a highly prevalent cation in the brain, have provided new insights that may help to rekindle the enthusiasm...
May 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/29740385/refocusing-neuroprotection-in-cerebral-reperfusion-era-new-challenges-and-strategies
#16
REVIEW
Xiao-Yi Xiong, Liang Liu, Qing-Wu Yang
Pathophysiological processes of stroke have revealed that the damaged brain should be considered as an integral structure to be protected. However, promising neuroprotective drugs have failed when translated to clinical trials. In this review, we evaluated previous studies of neuroprotection and found that unsound patient selection and evaluation methods, single-target treatments, etc., without cerebral revascularization may be major reasons of failed neuroprotective strategies. Fortunately, this may be reversed by recent advances that provide increased revascularization with increased availability of endovascular procedures...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29740308/cyclosporin-a-mediated-activation-of-endogenous-neural-precursor-cells-promotes-cognitive-recovery-in-a-mouse-model-of-stroke
#17
Labeeba Nusrat, Jessica M Livingston-Thomas, Vaakiny Raguthevan, Kelsey Adams, Ilan Vonderwalde, Dale Corbett, Cindi M Morshead
Cognitive dysfunction following stroke significantly impacts quality of life and functional independance; yet, despite the prevalence and negative impact of cognitive deficits, post-stroke interventions almost exclusively target motor impairments. As a result, current treatment options are limited in their ability to promote post-stroke cognitive recovery. Cyclosporin A (CsA) has been previously shown to improve post-stroke functional recovery of sensorimotor deficits. Interestingly, CsA is a commonly used immunosuppressant and also acts directly on endogenous neural precursor cells (NPCs) in the neurogenic regions of the brain (the periventricular region and the dentate gyrus)...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29734653/the-janus-face-of-vegf-in-stroke
#18
REVIEW
Samuel J Geiseler, Cecilie Morland
The family of vascular endothelial growth factors (VEGFs) are known for their regulation of vascularization. In the brain, VEGFs are important regulators of angiogenesis, neuroprotection and neurogenesis. Dysregulation of VEGFs is involved in a large number of neurodegenerative diseases and acute neurological insults, including stroke. Stroke is the main cause of acquired disabilities, and normally results from an occlusion of a cerebral artery or a hemorrhage, both leading to focal ischemia. Neurons in the ischemic core rapidly undergo necrosis...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29725905/jm-20-treatment-after-mcao-reduced-astrocyte-reactivity-and-neuronal-death-on-peri-infarct-regions-of-the-rat-brain
#19
Jeney Ramírez-Sánchez, Elisa Nicoloso Simões Pires, André Meneghetti, Gisele Hansel, Yanier Nuñez-Figueredo, Gilberto L Pardo-Andreu, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, René Delgado-Hernández, Christianne Salbego, Diogo O Souza
Stroke is frequently associated with severe neurological decline and mortality, and its incidence is expected to increase due to aging population. The only available pharmacological treatment for cerebral ischemia is thrombolysis, with narrow therapeutic windows. Efforts aimed to identify new therapeutics are crucial. In this study, we look into plausible molecular and cellular targets for JM-20, a new hybrid molecule, against ischemic stroke in vivo. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) following 23 h of reperfusion...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29725299/octadecylpropyl-sulfamide-reduces-neurodegeneration-and-restores-the-memory-deficits-induced-by-hypoxia-ischemia-in-mice
#20
Elk Kossatz, Daniel Silva-Peña, Juan Suárez, Fernando R de Fonseca, Rafael Maldonado, Patricia Robledo
The PPAR-α agonist, oleoylethanolamide (OEA) has neuroprotective properties in stroke models. However, its rapid degradation represents a limitation for an effective therapeutic approach. In this study, we evaluated the effects of a stable OEA-modeled compound, octadecylpropyl sulfamide (SUL) on the cognitive, behavioral, cellular and molecular alterations associated with hypoxia-ischemia (HI) in mice. Mice subjected to HI were treated with the PPAR-α antagonist GW6471 (GW) (1 mg/kg) followed 15 min later by SUL (3 and 10 mg/kg)...
2018: Frontiers in Pharmacology
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