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Stroke neuroprotective

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https://www.readbyqxmd.com/read/29345255/pure-mechanistic-analysis-of-additive-neuroprotective-effects-between-baicalin-and-jasminoidin-in-ischemic-stroke-mice
#1
Peng-Qian Wang, Qiong Liu, Wen-Juan Xu, Ya-Nan Yu, Ying-Ying Zhang, Bing Li, Jun Liu, Zhong Wang
Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Mice with middle cerebral artery obstruction were treated with BA, JA, their combination (BJ), or concha margaritifera (CM)...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344420/the-effects-of-baicalin-and-baicalein-on-cerebral-ischemia-a-review
#2
REVIEW
Wei Liang, Xiaobo Huang, Wenqiang Chen
Ischemic stroke, producing a high mortality and morbidity rate, is a common clinical disease. Enhancing the prevention and control of ischemic stroke is particularly important. Baicalin and its aglycon baicalein are flavonoids extracted from Scutellaria baicalensis, an important traditional Chinese herb. In recent years, a growing body of evidences has shown that baicalin and baicalein could be effective in the treatment of cerebral ischemia. Pharmacokinetic studies have shown that baicalin could penetrate the blood-brain barrier and distribute in cerebral nuclei...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29343482/par1-biased-signaling-is-required-for-activated-protein-c-in-vivo-benefits-in-sepsis-and-stroke
#3
Ranjeet K Sinha, Yaoming Wang, Zhen Zhao, Xiao Xu, Laurent Burnier, Naveen Gupta, José A Fernandez, Greg Martin, Sergey Kupriyanov, Laurent O Mosnier, Berislav V Zlokovic, John H Griffin
Activated Protein C (APC) cleaves protease activated receptor (PAR)1 in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of pharmacologic APC's in vivo mechanisms, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1 homozygous mutations that prevent cleavage at either R41 or R46...
January 17, 2018: Blood
https://www.readbyqxmd.com/read/29342116/vegf-signaling-in-neurological-disorders
#4
REVIEW
Joon W Shim, Joseph R Madsen
Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF)-a class of EGF receptor (EGFR) family ligands-contributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29338172/activation-of-nrf2-and-hypoxic-adaptive-response-contribute-to-neuroprotection-elicited-by-phenylhydroxamic-acid-selective-hdac6-inhibitors
#5
Irina N Gaisina, Sue H Lee, Navneet A Kaidery, Manel Ben Aissa, Manuj Ahuja, Natalya N Smirnova, Sushama Wakade, Arsen Gaisin, Megan W Bourassa, Rajiv R Ratan, Sergey V Nikulin, Andrey A Poloznikov, Bobby Thomas, Gregory R J Thatcher, Irina G Gazaryan
Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase (HDAC) inhibitors as potential activators of these pathways. We report the identification of phenylhydroxamates as single agents exhibiting tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and activation of Nrf2...
January 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29337840/targeted-temperature-management-at-33%C3%A2-c-or-36%C3%A2-c-produces-equivalent-neuroprotective-effects-in-the-middle-cerebral-artery-occlusion-rat-model-of-ischemic-stroke
#6
Jung Ho Lee, Jisoo Lim, Yong Eun Chung, Sung Phil Chung, Incheol Park, Chul Hoon Kim, Je Sung You
Targeted temperature management (TTM, 32°C to 36°C) is one of the most successful achievements in modern resuscitation medicine. It has become standard treatment for survivors of sudden cardiac arrest to minimize secondary brain damage. TTM at 36°C is just as effective as TTM at 33°C and is actually preferred because it reduces adverse TTM-associated effects. TTM also likely has direct neuroprotective effects in ischemic brains in danger of stroke. It remains unclear, however, whether higher temperature TTM is equally effective in protecting the brain from the effects of stroke...
January 15, 2018: Shock
https://www.readbyqxmd.com/read/29336466/magnolol-protects-against-ischemic-reperfusion-brain-damage-following-oxygen-glucose-deprivation-and-transient-focal-cerebral-ischemia
#7
Sheng-Yang Huang, Shih-Huang Tai, Che-Chao Chang, Yi-Fang Tu, Chih-Han Chang, E-Jian Lee
In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin‑6, tumor necrosis factor‑a and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygen‑glucose deprivation‑induced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29335619/cytokine-mif-enhances-blood-brain-barrier-permeability-impact-for-therapy-in-ischemic-stroke
#8
Yu-Chuan Liu, Yung-Hsu Tsai, Sung-Chun Tang, Houng-Chi Liou, Kai-Hsiang Kang, Horng-Huei Liou, Jiann-Shing Jeng, Wen-Mei Fu
Ischemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated. To figure out the pathological role of MIF in ischemic stroke, both in vitro and in vivo studies were conducted. For in vitro studies, primary cortical neuron cultures and adult rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were used for in vivo studies...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29332564/mesenchymal-stem-cell-therapy-in-intracerebral-haemorrhagic-stroke
#9
Gloria Bedini, Anna Bersano, Elisa R Zanier, Francesca Pischiutta, Eugenio A Parati
BACKGROUND: Spontaneous intracerebral haemorrhage (ICH) is a relatively common fatal disease, with an overall global incidence estimated at 24.6 per 100,000 person-years. Given the high degree of morbidity and mortality associated with ICH, therapies that may have neuroprotective effects are of increasing interest to clinicians. In this last context, cell therapies offer the promise of improving the disease course which cannot be addressed adequately by existing treatments. OBJECTIVE: The aim of this review is to evaluate the protective effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic brain following ICH...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29323156/ischemia-induced-neuronal-cell-death-is-mediated-by-chemokine-receptor-cx3cr1
#10
Jinkun Wang, Yan Gan, Pengcheng Han, Junxiang Yin, Qingwei Liu, Soha Ghanian, Feng Gao, Guanghui Gong, Zhiwei Tang
The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke. Previous studies have focused on a paracrine interaction between neurons that produce fractalkine and microglia that express CX3CR1 receptors in the central nervous system. Recent findings have demonstrated the functional expression of CX3CR1 receptors by hippocampal neurons, suggesting their involvement in neuroprotective and neurodegenerative actions. To elucidate the roles of neuronal CX3CR1 in neurodegeneration induced by ischemic stroke, a mouse model of permanent middle cerebral artery occlusion (pMCAO) was employed...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323048/topiramate-as-a-neuroprotective-agent-in-a-rat-model-of-spinal-cord-injury
#11
Firat Narin, Sahin Hanalioglu, Huseyin Ustun, Kamer Kilinc, Burcak Bilginer
Topiramate (TPM) is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI). After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg) was given at 12-hour intervals for four times orally...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321391/-prothymosin%C3%AE-as-a-neuroprotective-damps-alarmins-molecule
#12
Hiroshi Ueda, Shiori Maeda
Prothymosin alpha (ProTα) has been identified as an anti-necrotic factor from the conditioned medium of primary cultured of rat cortical neurons under the serum-free starving condition. ProTα is released in a non-vesicular manner from neurons or astrocytes by the help of cargo protein S100A13. Thus released ProTα is found to have robustness roles in the brain under the condition of neuronal necrosis or apoptosis. ProTα inhibits necrosis by plasma membrane-translocation of glucose transporters endocytosed by ischemia/starving stress, through an activation of unidentified G protein-coupled receptor and protein kinase Cβ...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29318974/-understanding-the-role-of-hypoxia-inducible-factor-during-neurodegeneration-for-new-therapeutics-opportunities
#13
Amalia Merelli, Julio Cesar Garcia Rodriguez, Jaume Folch, Marcelo R Regueiro, Antoni Camins, Lazarowski Alberto
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages...
January 10, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29316653/synergistic-association-of-valproate-and-resveratrol-reduces-brain-injury-in-ischemic-stroke
#14
Lara Faggi, Giuseppe Pignataro, Edoardo Parrella, Vanessa Porrini, Antonio Vinciguerra, Pasquale Cepparulo, Ornella Cuomo, Annamaria Lanzillotta, Mariana Mota, Marina Benarese, Paolo Tonin, Lucio Annunziato, PierFranco Spano, Marina Pizzi
Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29315863/activatable-protein-nanoparticles-for-targeted-delivery-of-therapeutic-peptides
#15
Xi Yu, Xingchun Gou, Peng Wu, Liang Han, Daofeng Tian, Fengyi Du, Zeming Chen, Fuyao Liu, Gang Deng, Ann T Chen, Chao Ma, Jun Liu, Sara M Hashmi, Xing Guo, Xiaolong Wang, Haitian Zhao, Xinran Liu, Xudong Zhu, Kevin Sheth, Qianxue Chen, Louzhen Fan, Jiangbing Zhou
Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization...
January 8, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29315561/faim2-contributes-to-neuroprotection-by-erythropoietin-in-transient-brain-ischemia
#16
Daniel Komnig, Karen Gertz, Pardes Habib, Kay W Nolte, Tareq Meyer, Marc A Brockmann, Matthias Endres, Birgit Rathkolb, Martin Hrabě de Angelis, Jörg B Schulz, Björn H Falkenburger, Arno Reich
Delayed cell death in the penumbra region of acute ischemic stroke occurs through apoptotic mechanisms, making it amenable to therapeutic interventions. Fas/CD95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas/CD95 signaling is modulated by Fas-apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (EPO) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway, which regulates Faim2 expression...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29312600/mild-hypothermia-modulates-the-expression-of-nestin-and-caspase-3-in-the-sub-granular-zone-and-improves-neurological-outcomes-in-rats-with-ischemic-stroke
#17
Dan Yu, Xueying Wang, Feng Zhou, Liang Wang, Guoshuai Yang, Wei Zhong, Ying Li, Zhiping Zhou, Aiyue Wang, Yanhui Zhou
We assessed neurological outcomes, infarct volume, and the expression of nestin and caspase-3 in the hippocampal dentate gyrus following middle cerebral artery occlusion (MCAO) followed by reperfusion, with mild hypothermia (MH) treatment at the onset of ischemia in a MCAO rat model. Reperfusion began 2 hours after the MCAO model was set-up. MH treatment began at the onset of ischemia and was maintained for 4 hours. We evaluated neurological deficit score, brain infarct volumes, along with the immunohistochemical staining of nestin and caspase-3 in the sub-granular zone of the injured hemisphere on the 1st, 3rd, 7th, and 14th day after the onset of ischemia...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311641/blockade-of-soluble-epoxide-hydrolase-attenuates-post-ischemic-neuronal-hyperexcitation-and-confers-resilience-against-stroke-with-trkb-activation
#18
Li-Hsin Chang, Hui-Ching Lin, Shiang-Suo Huang, I-Chih Chen, Kai-Wen Chu, Chun-Lien Chih, Yao-Wen Liang, Yi-Chung Lee, You-Yin Chen, Yi-Hsuan Lee, I-Hui Lee
Inhibition and deletion of soluble epoxide hydrolase (sEH) has been suggested to ameliorate infarction in experimental ischemic stroke possibly via vasoactive epoxyeicosatrienoic acids. However, it is unknown whether the neuroprotective mechanisms involve alteration of post-ischemic neuronal transmission and neurotrophic signaling. We used a permanent middle cerebral artery occlusion (MCAO) model in adult wild-type mice with the sEH inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA) post-treatment and in sEH knockout (sEH KO) mice...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29304004/effects-of-fluoxetine-on-hippocampal-neurogenesis-and-neuroprotection-in-the-model-of-global-cerebral-ischemia-in-rats
#19
Marina Khodanovich, Alena Kisel, Marina Kudabaeva, Galina Chernysheva, Vera Smolyakova, Elena Krutenkova, Irina Wasserlauf, Mark Plotnikov, Vasily Yarnykh
A selective serotonin reuptake inhibitor, fluoxetine, has recently attracted a significant interest as a neuroprotective therapeutic agent. There is substantial evidence of improved neurogenesis under fluoxetine treatment of brain ischemia in animal stroke models. We studied long-term effects of fluoxetine treatment on hippocampal neurogenesis, neuronal loss, inflammation, and functional recovery in a new model of global cerebral ischemia (GCI). Brain ischemia was induced in adult Wistar male rats by transient occlusion of three main vessels originating from the aortic arch and providing brain blood supply...
January 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29302794/evaluation-of-the-neuroprotective-effect-of-sirt3-in-experimental-stroke
#20
Rajkumar Verma, Rodney M Ritzel, Joshua Crapser, Brett D Friedler, Louise D McCullough
Sirtuins (Sirt) are a family of NAD+ dependent histone deacetylase (HDAC) proteins implicated in aging, cell cycle regulation, and metabolism. These proteins are involved in the epigenetic modification of neuromodulatory proteins after strokevia acetylation/deacetylation. The specific role of Sirt3, a mitochondrial sirtuin, in post-stroke injury has been relatively unexplored. Using male Sirt3 knockout (KO) mice and wild-type littermates (WT), we show that Sirt3 KO mice show significant neuroprotection at 3 days after ischemia/reperfusion (I/R) or stroke injury...
January 4, 2018: Translational Stroke Research
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