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https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#1
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#2
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28210215/tryptanthrin-suppresses-the-activation-of-the-lps-treated-bv2-microglial-cell-line-via-nrf2-ho-1-antioxidant-signaling
#3
Young-Won Kwon, So Yeong Cheon, Sung Yun Park, Juhyun Song, Ju-Hee Lee
Microglia are the resident macrophages in the central nervous system (CNS) and play essential roles in neuronal homeostasis and neuroinflammatory pathologies. Recently, microglia have been shown to contribute decisively to neuropathologic processes after ischemic stroke. Furthermore, natural compounds have been reported to attenuate inflammation and pathologies associated with neuroinflammation. Tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) is a phytoalkaloid with known anti-inflammatory effects in cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28210211/app-as-a-protective-factor-in-acute-neuronal-insults
#4
REVIEW
Dimitri Hefter, Andreas Draguhn
Despite its key role in the molecular pathology of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28203483/galanin-protects-from-caspase-8-12-initiated-neuronal-apoptosis-in-the-ischemic-mouse-brain-via-galr1
#5
Yun Li, Zhu Mei, Shuiqiao Liu, Tong Wang, Hui Li, Xiao-Xiao Li, Song Han, Yutao Yang, Junfa Li, Zhi-Qing David Xu
Galanin (GAL) plays key role in many pathophysiological processes, but its role in ischemic stroke remains unclear. Here, the models of 1 h middle cerebral artery occlusion (MCAO)/1-7 d reperfusion (R)-induced ischemic stroke and in vitro cell ischemia of 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation in primary cultured cortical neurons were used to explore GAL's effects and its underlying mechanisms. The results showed significant increases of GAL protein levels in the peri-infarct region (P) and infarct core (I) within 48 h R of MCAO mice (p<0...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28199737/inhibition-of-trpv1-confers-neuroprotection-reduces-tnf-%C3%AE-and-increases-il-10-in-a-rat-stroke-model
#6
Elham Hakimizadeh, Ali Shamsizadeh, Ali Roohbakhsh, Mohammad Kazemi Arababadi, Mohammad Reza Hajizadeh, Mehdi Shariati, Mohammad Reza Rahmani, Mohammad Allahtavakoli
Stroke is a major cause of mortality and long-term disability in adults. TRPV1 plays a crucial role in neuroinflammation. In the current study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke...
February 15, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28198092/the-burden-of-neurological-disease-in-the-united-states-a-summary-report-and-call-to-action
#7
EDITORIAL
Clifton L Gooch, Etienne Pracht, Amy R Borenstein
: The United States carries a substantial fiscal burden resulting from the nearly 100 million Americans with neurological disease. The combined annual costs of Alzheimer's and other dementias, low back pain, stroke, traumatic brain injury, migraine, epilepsy, multiple sclerosis, spinal cord injury and Parkinson's disease totals nearly 800 billion dollars and is rapidly rising due to the aging of the U.S. POPULATION: We provide a summary overview of the substantial current and future economic impact of neurological disease, and provide an action plan for reducing this burden through neurological research and enhanced clinical management of neurological disorders in the United States...
February 15, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28196366/pre-treatment-of-17%C3%AE-estradiol-attenuates-cerebral-ischemia-induced-blood-brain-barrier-disruption-in-aged-rats-involvement-of-antioxidant-signaling
#8
Han Xiao, Mingyang Deng, Binbin Yang, Zhiping Hu, Jianguang Tang
BACKGROUND/AIMS: The blood-brain barrier (BBB) disruption is often induced in brain injury and particularly associated with cerebral ischemia in stroke. Estradiol, an endogenous steroid hormone, has been reported to play a protective role against cerebrovascular pathologies. Here we aimed to determine the potential effects of estradiol (17β-estradiol 3-benzoate, E2) on the integrity of BBB and brain damage following middle carotid artery occlusion (MCAO). METHODS: Aged ovariectomized female rats (24-month-old) were administered E2 for two months by daily intraperitoneal injections, prior to the induction of MCAO...
February 15, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28195646/ns1209-spd-502-a-novel-selective-ampa-antagonist-for-stroke-neuropathic-pain-or-epilepsy-drug-development-lessons-learned
#9
Jan M Keppel Hesselink
Preclinical Research The selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain...
February 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28194647/cofilin-mediates-lps-induced-microglial-cell-activation-and-associated-neurotoxicity-through-activation-of-nf-%C3%AE%C2%BAb-and-jak-stat-pathway
#10
Qasim Alhadidi, Zahoor A Shah
Microglial cells are activated in response to different types of injuries or stress in the CNS. Such activation is necessary to get rid of the injurious agents and restore tissue homeostasis. However, excessive activation of microglial cells is harmful and contributes to secondary injury. Pertinently, microglial cell activity was targeted in many preclinical and clinical studies but such strategy failed in clinical trials. The main reason behind the failed attempts is the complexity of the injury mechanisms which needs either a combination therapy or targeting a process that is involved in multiple pathways...
February 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28191863/ulinastatin-downregulates-tlr4-and-nf-kb-expression-and-protects-mouse-brains-against-ischemia-reperfusion-injury
#11
Xiaofang Li, Likai Su, Xiangjian Zhang, Cong Zhang, Lina Wang, Yaoru Li, Ye Zhang, Tingting He, Xingyuan Zhu, Lili Cui
BACKGROUND: Inflammatory damage plays an important role in ischemic stroke and provides potential targets for therapy. Ulinastatin (UTI), a drug used to treat shock and acute pancreatitis in clinic, has attracted attention for its protective effects through immunomodulatory and anti-inflammatory properties. However, the effect of UTI in the acute phase of cerebral ischemia/reperfusion (I/R) is not clear. This study is to investigate the potential neuroprotective effect of UTI and explore its underlying mechanisms...
February 13, 2017: Neurological Research
https://www.readbyqxmd.com/read/28188219/distinct-effects-of-mir-210-reduction-on-neurogenesis-increased-neuronal-survival-of-inflammation-but-reduced-proliferation-associated-with-mitochondrial-enhancement
#12
Ludmila A Voloboueva, Xiaoyun Sun, Lijun Xu, Yi-Bing Ouyang, Rona G Giffard
Neurogenesis is essential to brain development, and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSC). However, the survival of young neurons is sharply reduced by post-injury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28187508/the-role-of-adiponectin-receptors-in-the-regulation-of-synaptic-transmission-in-the-hippocampus
#13
Filippo Weisz, Sonia Piccinin, Dalila Mango, Richard Teke Ngomba, Nicola B Mercuri, Ferdinando Nicoletti, Robert Nisticò
In the last two decades adiponectin, member of the adipokines family, gained attention because of its unique antidiabetic effects. However, the presence in the brain of adiponectin receptors and adiponectin itself raised interest because of the possible association with neuropsychiatric diseases. Indeed, clinical studies found altered concentration of adiponectin both in plasma and cerebrospinal fluid in seeveral pathologies including depression, multiple sclerosis, Alzheimer's disease and stroke. Moreover, recent preclinical studies also suggest its involvement in different physiological functions...
February 10, 2017: Synapse
https://www.readbyqxmd.com/read/28183451/the-novel-exercise-induced-hormone-irisin-protects-against-neuronal-injury-via-activation-of-the-akt-and-erk1-2-signaling-pathways-and-contributes-to-the-neuroprotection-of-physical-exercise-in-cerebral-ischemia
#14
Dong-Jie Li, Yong-Hua Li, Hong-Bin Yuan, Le-Feng Qu, Pei Wang
BACKGROUND: Irisin is a novel exercise-induced myokine involved in the regulation of adipose browning and thermogenesis. In this study, we investigated the potential role of irisin in cerebral ischemia and determined whether irisin is involved in the neuroprotective effect of physical exercise in mice. MATERIALS AND METHODS: The middle cerebral artery occlusion (MCAO) model was used to produce cerebral ischemia in mice. First, the plasma irisin levels and changes in expression of the irisin precursor protein FNDC5 in skeletal muscle were determined post ischemic stroke...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28181668/nsi-189-a-small-molecule-with-neurogenic-properties-exerts-behavioral-and-neurostructural-benefits-in-stroke-rats
#15
Naoki Tajiri, David M Quach, Yuji Kaneko, Stephanie Wu, David Lee, Tina Lam, Ken L Hayama, Thomas G Hazel, Karl Johe, Michael C Wu, Cesar V Borlongan
Enhancing neurogenesis may be a powerful stroke therapy. Here, we tested in a rat model of ischemic stroke the beneficial effects of NSI-189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti-depressant drug in a clinical trial (Fava et al., 2015) and being tested in a Phase 2 efficacy trial (ClinicalTrials.gov, 2016) for treatment of major depression. Oral administration of NSI-189 in adult Sprague-Dawley rats starting at 6 hours after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke-induced motor and neurological deficits, which was maintained up to 24 weeks post-stroke...
February 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28178410/strategies-to-extend-thrombolytic-time-window-for-ischemic-stroke-treatment-an-unmet-clinical-need
#16
REVIEW
Ike Dela Peña, Cesar Borlongan, Guofang Shen, Willie Davis
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment...
January 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28178380/pre-ischemia-melatonin-treatment-alleviated-acute-neuronal-injury-after-ischemic-stroke-by-inhibiting-er-stress-dependent-autophagy-via-perk-and-ire1-signalings
#17
Dayun Feng, Bao Wang, Lei Wang, Neeta Abraham, Kai Tao, Lu Huang, Wei Shi, Yushu Dong, Yan Qu
Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre-ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR) related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion (MCAO) mouse model. Pre-ischemia melatonin treatment was able to attenuate IR-induced ER stress and autophagy...
February 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28176622/the-tlr9-antagonist-icpg-odn-at-different-dosages-inhibits-cerebral-ischemia-reperfusion-injury-in-mice
#18
Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong Dong, Lingna Deng Deng, Yidong Wang
Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear. This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion. Neurological function, infarct size, splenocytes and the expression of TLR9 and the downstream products of the TLR9 pathways were determined after cerebral I/R for up to 72 hours...
February 6, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28174023/hydrogen-sulfide-in-stroke-protective-or-deleterious
#19
REVIEW
Su Jing Chan, Peter T-H Wong
Hydrogen sulfide is believed to be a signalling molecule in the central nervous system. It is known to increase rapidly following an ischemic insult in experimental stroke. Is it protective or deleterious? This review surveys the relevant information available in the literature. It appears that there is no definitive answer to this question at present. Current evidence seems to suggest that the presence of H2S in the ischemic brain may either be deleterious or protective depending on its concentration, deleterious when high and protective when low...
February 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28169530/intranasal-pretreatment-with-z-ligustilide-the-main-volatile-component-of-rhizoma-chuanxiong-confers-prophylaxis-against-cerebral-ischemia-via-nrf2-and-hsp70-signaling-pathways
#20
Juan Li, Jie Yu, Hui Ma, Na Yang, Li Li, Ding-Ding Zheng, Ming-Xia Wu, Zhi-Long Zhao, Hong-Yi Qi
Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0...
February 16, 2017: Journal of Agricultural and Food Chemistry
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