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Stroke neuroprotective

Masaki Naganuma, Yuichiro Inatomi, Makoto Nakajima, Toshiro Yonehara, Yukio Ando
BACKGROUND: Uric acid (UA), an antioxidant with neuroprotective effects, favorably affects stroke outcome. However, the effect has not been examined in patients treated with edaravone, a frequently used free radical scavenger. We investigated whether the use of edaravone affected the relationship between UA levels and outcome in acute ischemic stroke. METHODS: We retrospectively evaluated 1,114 consecutive ischemic stroke patients with premorbid modified Rankin Scale (mRS) scores <2 admitted within 24 h of onset (mean, 74 years; median UA levels, 333 μmol/L)...
March 20, 2018: Cerebrovascular Diseases
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
Pingping Xia, Yundan Pan, Fan Zhang, Na Wang, E Wang, Qulian Guo, Zhi Ye
BACKGROUND/AIMS: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. METHODS: The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD)...
March 13, 2018: Cellular Physiology and Biochemistry
Roberta Gualdani, Maria Maddalena Cavalluzzi, Francesco Tadini-Buoninsegni, Marino Convertino, Philippe Gailly, Anna Stary-Weinzinger, Giovanni Lentini
BACKGROUND/AIMS: Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in preclinical models of ischemic stroke. However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. Since the cardiac cellular effects of lubeluzole have not been described thus far, an explanation for the lubeluzole-induced QT interval prolongation is lacking. METHODS: We tested the affinity of lubeluzole, its enantiomer, and the racemate for hERG channel using the patch-clamp technique...
March 10, 2018: Cellular Physiology and Biochemistry
Dandan Yao, Lei Zhang, Jiaojiao Huang, Chenghong Sun, Yu Zhang, Xiaoli Gu, Chong-Zhi Wang, Fei Li, Lina Chen, Chun-Su Yuan
In this work, surface magnetic molecularly imprinted polymers (SMMIPs) were synthesized and used as artificial receptors in the dispersive magnetic solid phase extraction (DMSPE) for capturing potential neuronal nitric oxide synthase-post synaptic density protein-95 (nNOS-PSD-95) uncouplers, which is known as neuroprotection against stroke. Factors that affected selective separation and adsorption of the artificial receptors, such as the amount of template, the types of functional monomer and porogen solvents, and the molar ratio of template/functional monomer/cross-linker were optimized...
March 3, 2018: Journal of Pharmaceutical and Biomedical Analysis
Sixtine Gilliot, Igor Sibon, Jean-Louis Mas, Thierry Moulin, Yannick Béjot, Charlotte Cordonnier, Maurice Giroud, Pascal Odou, Régis Bordet, Denis Vivien, Didier Leys
BACKGROUND: Many patients who receive intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA) for acute cerebral ischemia were under angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) at stroke onset. ACE-Is and ARBs have neuroprotective properties in animal models. OBJECTIVE: To evaluate whether the 3-month outcome of patients treated with i.v. rt-PA for cerebral ischemia was influenced by on-going therapy with ACE-Is or ARBs...
March 16, 2018: Journal of Neurology
Varinder Singh, Pawan Krishan, Richa Shri
Oxidative stress is strongly implicated in the pathogenesis of stroke. Strategies using antioxidants to improve neurological functions after stroke have, thus, gained significant attention. Ocimum basilicum L. is used traditionally to treat CNS disorders. Its antioxidant capacity is well established. Our laboratory has reported protective effects of pre-treatment with O. basilicum in experimental stroke, but its curative (post-treatment) effects in ischemic stroke have not been documented. Hence, the present study was aimed to evaluate the effect of O...
March 15, 2018: Metabolic Brain Disease
Giulia Cisbani, Audrey Le Behot, Marie-Michèle Plante, Paul Préfontaine, Manon Lecordier, Serge Rivest
Stroke is the second cause of mortality worldwide and occurs following the interruption of cerebral blood circulation by cerebral vessel burst or subsequent to a local thrombus formation. Ischemic lesion triggers an important inflammatory response, characterized by massive infiltration of leukocytes, activation of glial cells and neurovascular reorganization. Chemokines and their receptors, such as CCR2 and CX3CR1, play an important role in leukocyte recruitment in the damaged area. Mice genetically depleted for the two receptors CCR2 and CX3CR1 underwent focal cerebral ischemia, based on the topical application of ferric chloride to truncate the distal middle cerebral artery...
March 12, 2018: Brain, Behavior, and Immunity
Bruce Cv Campbell, Mark W Parsons
This review summarizes the current state of knowledge regarding the use of imaging to guide stroke treatment. Brain imaging plays a central role in the diagnosis of stroke and identification of the mechanism of stroke, which is relevant to acute treatment, prognosis, and secondary prevention. The chief potential modalities are computed tomography (CT) and magnetic resonance imaging (MRI). Currently, most imaging occurs in hospital but mobile stroke units have expanded CT brain imaging into the prehospital field...
January 1, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
Wen Zhang, Jun-Ke Song, Rong Yan, Li Li, Zhi-Yong Xiao, Wen-Xia Zhou, Zhen-Zhong Wang, Wei Xiao, Guan-Hua Du
Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion...
March 15, 2018: Acta Pharmacologica Sinica
Charles K Davis, Sreekala S Nampoothiri, G K Rajanikant
The constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay...
March 14, 2018: Molecular Neurobiology
Mei Jiang, Xinghui Liu, Denghai Zhang, Ying Wang, Xiaoxia Hu, Fengxia Xu, Mingming Jin, Fanfan Cao, Limin Xu
BACKGROUND: Acute ischemic stroke (AIS) is the most common type of cerebrovascular disease and is a leading cause of disability and death worldwide. Recently, a study suggested that transformation of microglia from the pro-inflammatory M1 state to the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. Celastrol, a traditional oriental medicine, may have anti-inflammatory and neuroprotective effects. However, the underlying mechanisms remain unknown...
March 14, 2018: Journal of Neuroinflammation
Tauheed Ishrat, Abdelrahman Y Fouda, Bindu Pillai, Wael Eldahshan, Heba Ahmed, Jennifer L Waller, Adviye Ergul, Susan C Fagan
The aim of this translational, randomized, controlled, blinded preclinical trial was to determine the effect of compound 21 (C21) in embolic stroke. Rats were subjected to embolic-middle cerebral artery occlusion (eMCAO). They received C21 (0.01, 0.03 and 0.06 mg/kg/d) or saline (orally) for five days, with the first-dose given IV at 3 h post-eMCAO. For the time-window study, the optimal-dose of C21 was initiated at 3, 6 or 24 h post-eMCAO and continued for five days. For the combinatorial study, animals received IV-tissue plasminogen activator (tPA) at either 2 or 4 h, with IV-C21 (0...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Yin-Feng Dong, Ruo-Bing Guo, Juan Ji, Lu-Lu Cao, Ling Zhang, Zheng-Zhen Chen, Ji-Ye Huang, Jin Wu, Jun Lu, Xiu-Lan Sun
Fingolimod (FTY720) is used as an immunosuppressant for multiple sclerosis. Numerous studies indicated its neuroprotective effects in stroke. However, the mechanism remains to be elucidated. This study was intended to investigate the mechanisms of phosphorylated FTY720 (pFTY720), which was the principle active molecule in regulating astrocyte-mediated inflammatory responses induced by oxygen-glucose deprivation (OGD). Results demonstrated that pFTY720 could protect astrocytes against OGD-induced injury and inflammatory responses...
March 13, 2018: Journal of Cellular and Molecular Medicine
Qiu Jing Wu, Michael Tymianski
NMDA (N-methyl-d-aspartate) receptors (NMDARs) play a central role in excitotoxic neuronal death caused by ischemic stroke, but NMDAR channel blockers have failed to be translated into clinical stroke treatments. However, recent research on NMDAR-associated signaling complexes has identified important death-signaling pathways linked to NMDARs. This led to the generation of inhibitors that inhibit these pathways downstream from the receptor without necessarily blocking NMDARs. This therapeutic approach may have fewer side effects and/or provide a wider therapeutic window for stroke as compared to the receptor antagonists...
March 13, 2018: Molecular Brain
Juan Zhang, Lorelei Donovan Tucker, DongYan, Yujiao Lu, Luodan Yang, Chongyun Wu, Yong Li, Quanguang Zhang
Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury...
March 9, 2018: Neurochemistry International
Yu Mao, Qiuyue Kong, Rongrong Li, Xiaojin Zhang, Yali Gui, Yuehua Li, Chuanfu Li, Yanlin Zhao, Li Liu, Zhengnian Ding
Heat shock protein A12A (HSPA12A) is a newly discovered member of the Hsp70 family. The biological characteristics and functional roles of HSPA12A are poorly understood. This study investigated the effects of HSPA12A on ischaemic stroke in mice. Ischaemic stroke was induced by left middle cerebral artery occlusion for 1 h followed by blood reperfusion. We observed that HSPA12A was highly expressed in brain neurons, and neuronal HSPA12A expression was downregulated by ischaemic stroke and stroke-associated risk factors (aging, obesity and hyperglycaemia)...
March 9, 2018: Biochimica et Biophysica Acta
Kelly M DeMars, Austin O McCrea, David M Siwarski, Brian D Sanz, Changjun Yang, Eduardo Candelario-Jalil
Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1-EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s) of protection are not well-characterized...
2018: Frontiers in Neuroscience
F H Cabrera Naranjo, P Saavedra Santana, A González Hernández, O Fabre Pi, M Sosa-Henríquez
INTRODUCTION: Recent studies on uric acid as a biomarker for the prognosis of acute stroke have found conflicting results. METHODS: We collected blood samples from 600 consecutively admitted patients at our tertiary hospital and analysed the relationship between uric acid levels and functional prognosis (measured using the modified Rankin Scale [mRS]). Patients who had received reperfusion therapy were excluded since this may have influenced uric acid levels. RESULTS: A total of 73% of patients had mRS scores ≤2; the mean uric acid level was 5...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang, Guo Zhong Li
OBJECTIVE Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke...
March 9, 2018: Journal of Neurosurgery
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