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Chung-Ching Chio, Mao-Tsun Lin, Ching-Ping Chang, Hung-Jung Lin
BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) regulates many processes after traumatic brain injury (TBI). Both Neuro AiD(™) (MLC601) and Astragaloside (AST) attenuate microglia activation in rats with TBI. The purpose of this study was to investigate whether MLC601 or AST improves output of TBI by affecting microglial expression of TGF-β1. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (120 in number) were used to investigate the contribution of TGF-β1-containing microglia in the MLC601-mediated or the AST-mediated neuroprotection in the brain trauma condition using lateral fluid-percussion injury...
October 19, 2016: European Journal of Clinical Investigation
Zühtü Özbek, Hasan Emre Aydin, Atacan Emre Koçman, Emre Özkara, Erdem Söztutar, Ezgi Bektur, Murat Vural, Aydan Köse, Ali Arslantaş, Cengiz Bayçu
AIM: In this study, we investigated the effects of genistein in a rat model of sciatic nerve crush injury and complete sciatic nerve transection. The effects of genistein were compared with those of gabapentin, which is widely used in clinical practice for peripheral nerve injury. MATERIAL AND METHODS: Forty-eight rats were randomly divided into six groups (n = 8 for all groups): group 1 (sham); group 2, sciatic nerve crush injury (control); group 3, sciatic nerve crush injury + genistein 20 mg/kg; group 4, sciatic nerve crush injury + gabapentin 90 mg/kg; group 5, sciatic nerve transection + genistein 20 mg/kg; group 6, sciatic nerve transection + gabapentin 90 mg/kg...
September 21, 2016: Turkish Neurosurgery
Nobuhiro Nagai, Satoru Iwata, Hirokazu Kaji, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Matsuhiko Nishizawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe
It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices...
November 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
M Asunción Barreda-Manso, Natalia Yanguas-Casás, Manuel Nieto-Sampedro, Lorenzo Romero-Ramírez
Following a central nervous system (CNS) injury, restoration of the blood-brain barrier (BBB) integrity is essential for recovering homeostasis. When this process is delayed or impeded, blood substances and cells enter the CNS parenchyma, initiating an additional inflammatory process that extends the initial injury and causes so-called secondary neuronal loss. Astrocytes and profibrotic mesenchymal cells react to the injury and migrate to the lesion site, creating a new glia limitans that restores the BBB. This process is beneficial for the resolution of the inflammation, neuronal survival and the initiation of the healing process...
October 18, 2016: Journal of Cellular Physiology
Ricarda A L Menke, Federica Agosta, Julian Grosskreutz, Massimo Filippi, Martin R Turner
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo...
October 17, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Youngsin Jung, Erik K St Louis
REM sleep behavior disorder (RBD) is a common parasomnia disorder affecting between 1 and 7 % of community-dwelling adults, most frequently older adults. RBD is characterized by nocturnal complex motor behavior and polysomnographic REM sleep without atonia. RBD is strongly associated with synucleinopathy neurodegeneration. The approach to RBD management is currently twofold: symptomatic treatment to prevent injury and prognostic counseling and longitudinal follow-up surveillance for phenoconversion toward overt neurodegenerative disorders...
November 2016: Current Treatment Options in Neurology
Leonard A Levin
Glaucoma is both the most common optic neuropathy worldwide and the most common cause of irreversible blindness in the world. The only proven treatment for glaucomatous optic neuropathy is lowering the intraocular pressure, achieved with a variety of pharmacological, laser, and surgical approaches. Over the past 2 decades there has been much basic and clinical research into achieving treatment of the underlying optic nerve damage with neuroprotective approaches. However, none has resulted in regulatory approval based on successful phase 3 studies...
October 18, 2016: Handbook of Experimental Pharmacology
Asad Jan, Brandon Jansonius, Alberto Delaidelli, Syam Prakash Somasekharan, Forum Bhanshali, Milène Vandal, Gian Luca Negri, Don Moerman, Ian MacKenzie, Frédéric Calon, Michael R Hayden, Stefan Taubert, Poul H Sorensen
Soluble oligomers of amyloid-β (Aβ) impair synaptic plasticity, perturb neuronal energy homeostasis, and are implicated in Alzheimer's disease (AD) pathogenesis. Therefore, significant efforts in AD drug discovery research aim to prevent the formation of Aβ oligomers or block their neurotoxicity. The eukaryotic elongation factor-2 kinase (eEF2K) plays a critical role in synaptic plasticity, and couples neurotransmission to local dendritic mRNA translation. Recent evidence indicates that Aβ oligomers activate neuronal eEF2K, suggesting a potential link to Aβ induced synaptic dysfunction...
October 17, 2016: Acta Neuropathologica
Ioanna Eleftheriadou, Ioannis Manolaras, Elaine E Irvine, Michael Dieringer, Antonio Trabalza, Nicholas D Mazarakis
OBJECTIVE: We have previously described the generation of coxsackievirus and adenovirus receptor (α CAR)-targeted vector, and shown that intramuscular delivery in mouse leg muscles resulted in specific retrograde transduction of lumbar-motor neurons (MNs). Here, we utilized the α CAR-targeted vector to investigate the in vivo neuroprotective effects of lentivirally expressed IGF-1 for inducing neuronal survival and ameliorating the neuropathology and behavioral phenotypes of the SOD1(G93A) mouse model of ALS...
October 2016: Annals of Clinical and Translational Neurology
Su Jin Kang, Ji Yeon Seo, Kye Man Cho, Chang Kwon Lee, Jeong Hwan Kim, Jong-Sang Kim
A new type of doenjang was manufactured by mixing soaked soybean, koji (Rhizopus oryzae), cheonggukjang (Bacillus amyloliquefaciens MJ1-4 and B. amyloliquefaciens EMD17), and Pichia farinosa SY80 as a yeast, salt, and water, followed by fermentation with koji that was made by fermenting whole wheat with R. oryzae. The mixed culture doenjang was designed to have a more palatable flavor and stronger biological activities than the conventional product. The extract of mixed culture doenjang showed higher antioxidant activity than the commercial doenjang as evaluated by the ferric reducing antioxidant power assay although it was not significantly different from the commercial product in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activities...
September 2016: Preventive Nutrition and Food Science
Alberto Ascherio, Michael A Schwarzschild
Since 2006, several longitudinal studies have assessed environmental or behavioural factors that seem to modify the risk of developing Parkinson's disease. Increased risk of Parkinson's disease has been associated with exposure to pesticides, consumption of dairy products, history of melanoma, and traumatic brain injury, whereas a reduced risk has been reported in association with smoking, caffeine consumption, higher serum urate concentrations, physical activity, and use of ibuprofen and other common medications...
November 2016: Lancet Neurology
Koning Shen, Barbara Calamini, Jonathan A Fauerbach, Boxue Ma, Sarah H Shahmoradian, Ivana L Serrano Lachapel, Wah Chiu, Donald C Lo, Judith Frydman
Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington's disease (HD), neurotoxicity correlates with increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation...
October 18, 2016: ELife
Shi-Fa Zhang, Yan Zhou, Kai-Jing Zhang, Jia-Jie Luan, Shi-Mei Qi
OBJECTIVE: To investigate the effect of Nogo-66 receptor (NgR) silencing with specific small interfering RNA (siRNA) on brain injury repair in preterm rats with brain injury caused by intrauterine infection and related mechanism of action. METHODS: The pregnant Sprague-Dawley rats (with a gestational age of 15 days) were selected, and premature delivery was induced by RU486 or lipopolysaccharide (LPS). The preterm rats delivered by those treated with RU486 were selected as the control group...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
John E Cebak, Indrapal N Singh, Rachel L Hill, Juan Wang, Edward D Hall
Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or the propagation of lipid peroxidation (LP). A more recently explored approach involves scavenging the terminal LP breakdown products that are highly reactive and neurotoxic carbonyl compounds 4-hydroxynonenal (4-HNE) and acrolein to prevent their covalent modification and rendering of cellular proteins non-functional leading to loss of ionic homeostasis, mitochondrial failure, and subsequent neuronal death...
October 18, 2016: Journal of Neurotrauma
Tapasi Rana, Pravallika Kotla, Roderick Fullard, Marina Gorbatyuk
Expression of T17M rhodopsin (T17M) in rods activates the Unfolded Protein Response (UPR) and leads to the development of autosomal dominant retinitis pigmentosa (adRP). The rod death occurs in adRP retinas prior to cone photoreceptor death, so the mechanism by which cone photoreceptors die remains unclear. Therefore, the goal of the study was to verify whether UPR in rods induces TNFa-mediated signaling to the cones and to determine whether the TNFa deficit could prevent adRP cone cell death. Primary rod photoreceptors and cone-derived 661W cells transfected with siRNA against TNFa were treated with tunicamycin to mimic activation of UPR in T17M retinas expressing normal and reduced TNFa levels...
October 14, 2016: Biochimica et Biophysica Acta
Bin Lin, Heng Yu, Yuting Lin, Chao Cai, Huoquan Lu, Xinbo Zhu
The aim of the present study was to assess the neuroprotective effects of tetrahydrocurcumin (THC) in a mouse model of cerebral ischemia/reperfusion (I/R) injury, and to investigate the involvement of Golgi reassembly and stacking protein 65 (GRASP65) and the extracellular signal‑regulated kinase (ERK) signaling pathway. Cerebral I/R injury was induced using the Pulsinelli four‑vessel occlusion method. After 5 min of reperfusion, mice received THC (5, 10 or 25 mg/kg) or saline by intraperitoneal injection...
October 6, 2016: Molecular Medicine Reports
Ying Li Gu, Guan Qun Gao, Ning Ma, Lin Lin Ye, Li Wei Zhang, Xu Gao, Zhuo Bo Zhang
The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system...
October 13, 2016: International Journal of Molecular Medicine
D K Rieger, E Navarro, I Buendia, E Parada, L González-Lafuente, R Leon, A P Costa, I A Heinrich, K S Nascimento, B S Cavada, M G Lopez, J Egea, R B Leal
Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 μg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD...
October 17, 2016: Neurochemical Research
Bassem Yousef Sheikh, S M Neamul Kabir Zihad, Nazifa Sifat, Shaikh J Uddin, Jamil A Shilpi, Omer A A Hamdi, Hemayet Hossain, Razina Rouf, Ismet Ara Jahan
In addition to the rich nutritional value, date palm is also used in various ethnobotanical practices for the treatment of various disease conditions. Present investigation was undertaken to examine the neuropharmacological and antinociceptive effect of the ethanol extract of three date cultivars growing in Saudi Arabia, namely Ajwah, Safawy and Sukkari. Neuropharmacological effect was observed by pentobarbitone induced sleeping time, open field, and hole board test. Antinociceptive activity was tested by acetic acid induced writhing and hot plate test...
2016: Oriental Pharmacy and Experimental Medicine
Haiyun Chen, Guolian Tan, Jie Cao, Gaoxiao Zhang, Peng Yi, Pei Yu, Yewei Sun, Zaijun Zhang, Yuqiang Wang
Oxidative stress plays a crucial role in neurological diseases, resulting in excessive production of reactive oxygen species, mitochondrial dysfunction and cell death. In this work, we designed and synthesized a series of tetramethylpyrazine derivatives and investigated their abilities for scavenging free radicals and preventing against oxidative stress-induced neuronal damage in vitro. Among them, compound 22a, consisted of TMP, caffeic acid and a nitrone group, showed potent radical-scavenging activity. Compound 22a had broad neuroprotective effects, including rescuing iodoacetic acid-induced neuronal loss, preventing from t-BHP-induced neuronal injury...
October 14, 2016: Chemical & Pharmaceutical Bulletin
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