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Jessica C Stark, Euan Wallace, Rebecca Lim, Bryan Leaw
Microglia, the resident immune cells in the brain, are the first responders to inflammation or injury in the central nervous system. Recent research has revealed microglia to be dynamic, capable of assuming both pro-inflammatory and anti-inflammatory phenotypes. Both M1 (pro-inflammatory) and M2 (pro-reparative) phenotypes play an important role in neuroinflammatory conditions such as perinatal brain injury, and exhibit differing functions in response to certain environmental stimuli. The modulation of microglial activation has been noted to confer neuroprotection thus suggesting microglia may have therapeutic potential in brain injury...
February 16, 2018: Journal of Visualized Experiments: JoVE
Rosalia Crupi, Daniela Impellizzeri, Marika Cordaro, Rosalba Siracusa, Giovanna Casili, Maurizio Evangelista, Salvatore Cuzzocrea
Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD induced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model...
March 19, 2018: Molecular Neurobiology
Dawei Lei, Zhengbo Shao, Xinrong Zhou, Huiping Yuan
Retinal ischemia-reperfusion (RIR) injury causes neuronal degeneration and initiates various optic nerve diseases. This study aimed to investigate the synergistic neuroprotective effect of rasagiline and idebenone against RIR injury. A combination of rasagiline and idebenone was administered intraperitoneally immediately after establishment of the RIR model. Treatment with the combination of the two drugs resulted in a significant restoration of retinal thickness and retinal ganglion cells. Apoptosis of cells in ganglion cell layers was also ameliorated, suggesting that the effect of the two drugs was synergistic and the expression of brain-derived neurotrophic factor increased...
February 23, 2018: Oncotarget
Raffaele Nuzzi, Simona Scalabrin, Alice Becco, Giancarlo Panzica
Aim: Gonadal hormones are essential for reproductive function, but can act on neural and other organ systems, and are probably the cause of the large majority of known sex differences in function and disease. The aim of this review is to provide evidence for this hypothesis in relation to eye disorders and to retinopathies in particular. Methods: Epidemiological studies and research articles were reviewed. Results: Analysis of the biological basis for a relationship between eye diseases and hormones showed that estrogen, androgen, and progesterone receptors are present throughout the eye and that these steroids are locally produced in ocular tissues...
2018: Frontiers in Endocrinology
Dinesh Kumar Verma, Sonam Gupta, Joyshree Biswas, Neeraj Joshi, Abhishek Singh, Parul Gupta, Shubhangini Tiwari, K Sivarama Raju, Swati Chaturvedi, M Wahajuddin, Sarika Singh
Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation...
March 15, 2018: Biochimica et Biophysica Acta
Yoko Hirata, Chika Yamada, Yuki Ito, Shotaro Yamamoto, Haruna Nagase, Kentaro Oh-Hashi, Kazutoshi Kiuchi, Hiromi Suzuki, Makoto Sawada, Kyoji Furuta
The current medical and surgical therapies for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease offer symptomatic relief but do not provide a cure. Thus, small synthetic compounds that protect neuronal cells from degeneration are critically needed to prevent and treat these. Oxidative stress has been implicated in various pathophysiological conditions, including neurodegenerative diseases. In a search for neuroprotective agents against oxidative stress using the murine hippocampal HT22 cell line, we found a novel oxindole compound, GIF-0726-r, which prevented oxidative stress-induced cell death, including glutamate-induced oxytosis and erastin-induced ferroptosis...
March 15, 2018: Neuropharmacology
Yue Cao, Christian Hölscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu Bai, Jun Zhang, Mei-Na Wu, Jin-Shun Qi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. The early primary symptom of AD is the decline of memory ability, which gradually develops into complete dementia. Type 2 diabetes mellitus (T2DM) is an important risk factor of AD; and mimetics of the incretin hormone GLP-1 developed to treat diabetes are being tested as a novel therapeutic strategy for AD. In the present study, we reported for the first time the neuroprotective effects of a novel GLP-1/GIP dual agonist DA5-CH that activates the incretin hormone GLP-1 and GIP receptors in the APP/PS1 transgenic AD mouse model...
March 15, 2018: European Journal of Pharmacology
Meysam Amidfar, Gislaine Z Réus, Joao Quevedo, Yong-Ku Kim
A developing body of evidence indicates that disturbed glutamate neurotransmission especially through N-methyl-d-aspartate (NMDA) is central to the pathophysiology of major depressive disorder (MDD) and NMDA receptor antagonists have shown therapeutic potential in the MDD treatment. Memantine is an uncompetitive NMDA receptor antagonist, approved for treatment of Alzheimer's disease (AD) that in contrast to other NMDA receptor antagonists at therapeutic doses does not induce highly undesirable side effects...
March 15, 2018: European Journal of Pharmacology
Ying Song, Yun Bei, Yan Xiao, Hai-Da Tong, Xie-Qi Wu, Man-Ting Chen
To investigate the neuroprotective effect of edaravone was dependent on 5-lipoxygenase (5-LOX) signalling pathway or not. Middle cerebral artery occlusion (MCAO) and oxygen glucose deprivation (OGD) were established in SD rats and PC12 cells to mimic ischemic injury. In vivo, edaravone can significantly reduce neurological deficit scores, infarct volume and expression of 5-LOX. For in vitro experiment, reduced viability, cell death which occurred via necrosis and apoptosis were shown after OGD and even severer in OGD-reperfusion (OGD-R)...
March 15, 2018: Brain Research
Sara Milanizadeh, Karrar Najm Najaf Zuwarali, Abbas Aliaghaei, Mohammad Reza Bigdeli
Brain ischemia is one of the most common causes of death and disability worldwide, which usually happens through diminished blood supply to the tissue. Cell therapy and treatments using trophic factors are some of the new methods to protect brain cells against damage. Specific properties of Sertoli cells (SCs) make them suitable for improving neurological disorders. This study is to evaluate possible neuroprotective effects of SCs transplantation on ischemic damage. Rats were divided into three experimental groups including sham, control, and SCs-treated group...
March 17, 2018: Journal of Molecular Neuroscience: MN
Wenqian Zhang, Ying Cui, Junling Gao, Ran Li, Xiaohua Jiang, Yanxia Tian, Kaijie Wang, Jianzhong Cui
BACKGROUND This study aimed to investigate the potential neuroprotective effect of recombinant osteopontin (r-OPN) on apoptotic changes via modulating phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK-3β) signaling in a rat model of intracerebral hemorrhage (ICH). MATERIAL AND METHODS We subjected 10-12-week-old Sprague-Dawley male rats (n=120) to injection of autologous blood into the right basal ganglia to induce ICH or sham surgery. ICH animals received vehicle administration, r-OPN (4 μL/pup), or r-OPN combined with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (86 ng/pup) at 30 min after injury...
March 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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
Zhiquan Lv, Chong Liu, Meili Zhai, Qian Zhang, Jun Li, Fang Zheng, Mingqing Peng
BACKGROUND/AIMS: Lipopolysaccharide (LPS) pretreatment has a strong neuroprotective effect on cerebral ischaemia/reperfusion injury (IRI), but the mechanism has not been fully elucidated to date. This study investigated the effect of LPS pretreatment on the pathway mediated by endoplasmic reticulum (ER) stress-CCAAT/enhancer-binding protein- homologous protein (CHOP) and the role of this pathway on cerebral ischaemia/reperfusion (I/R)-induced inflammation and apoptosis. METHODS: Healthy male BALB/c mice were randomised into four groups as follows: sham operation group (sham group, n=30); LPS group (BALB/c mice treated with LPS, n=30); ischaemia/reperfusion group (I/R group, n=30) and I/R+LPS group (BALB/c mice treated with LPS before ischaemia, n=30)...
March 10, 2018: Cellular Physiology and Biochemistry
Sheng Peng, Hong-Zhu Yan, Pei-Rong Liu, Xiao-Wei Shi, Chun-Liang Liu, Qi Liu, Yu Zhang
BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry...
March 13, 2018: Cellular Physiology and Biochemistry
I C Chis, A Clichici, A L Nagy, A Oros, C Catoi, S Clichici
Diabetic neuropathy (DN) is a frequent, serious and debilitating chronic complication of diabetes mellitus (DM). Hyperglycemia, oxidative and nitrosative stress are involved in causing nerve damage in several animals, humans and experimental models of diabetes. This study was designed to investigate the synergistic cumulative neuroprotective effect of quercetin administration and moderate exercise training on sciatic nerves injuries in streptozotocin (STZ)-diabetic rats. DM was induced in Wistar rats by intraperitoneal administration of STZ (60 mg/kg)...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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
Luis Velázquez-Pérez, Roberto Rodríguez-Labrada, Reidenis Torres-Vega, Ricardo Ortega-Sánchez, Jacqueline Medrano-Montero, Rigoberto González-Piña, Yaimeé Vázquez-Mojena, Georg Auburger, Ulf Ziemann
OBJECTIVE: Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS). METHODS: Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS...
March 15, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Chin-Tsang Yang, Guan-Ling Lu, Sheng-Feng Hsu, Iona MacDonald, Lih-Chu Chiou, Shih-Ya Hung, Yi-Hung Chen
Paeonol is a major constituent of the Chinese herb Moutan cortex radices. Recent studies report that paeonol has neuroprotective effects and improves impaired learning and memory. However, its underlying mechanisms by which paeonol contributes to synaptic transmission remain unclear. In this study, we found that paeonol increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs), but had no effect on the amplitude in rat hippocampal CA1 neurons...
March 14, 2018: European Journal of Pharmacology
Marietta Zita Poles, Nikolett Bódi, Mária Bagyánszki, Éva Fekete, András Tamás Mészáros, Gabriella Varga, Szilárd Szűcs, Anna Nászai, Liliána Kiss, Andrey V Kozlov, Mihály Boros, József Kaszaki
Our aim was to characterize the main components of the nitrosative response with quantitative changes of the nitrergic myenteric neurons in adjacent intestinal segments after transient superior mesenteric artery occlusion. We also tested the hypothesis that exogenous methane may modulate the evolution of nitroxidation by influencing xanthine oxidoreductase (XOR) activity. The microcirculatory consequences of a 50min ischemia or ischemia-reperfusion were investigated in anesthetized rats (n=124) inhaling normoxic air with or without 2...
March 14, 2018: Free Radical Biology & Medicine
Samaneh Sepahi, Seyed Ahmad Mohajeri, Seyedeh Maryam Hosseini, Elham Khodaverdi, Nasser Shoeibi, Maral Namdari, Sayyed Abolghasem Sajadi Tabassi
OBJECTIVE: Diabetic macular edema (DME) is one of the most important sight-threatening complications in patients with diabetes. Due to neuroprotective properties, crocin, as the main constituent in saffron, is thought to be useful in the treatment and prevention of diabetic maculopathy. The aim of this trial was to evaluate the effects of crocin as a supplement on reducing inflammation in patients with diabetic maculopathy. DESIGN: Double blind, placebo controlled, phase 2 randomized clinical trial...
March 14, 2018: American Journal of Ophthalmology
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