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Experimental Neurology

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https://www.readbyqxmd.com/read/28625590/intranasal-cotinine-improves-memory-and-reduces-depressive-like-behavior-and-gfap-cells-loss-induced-by-restraint-stress-in-mice
#1
Nelson Perez-Urrutia, Cristhian Mendoza, Nathalie Alvarez-Ricartes, Patricia Oliveros-Matus, Florencia Echeverria, J Alex Grizzell, George E Barreto, Alexandre Iarkov, Valentina Echeverria
Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress...
June 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28624361/low-intensity-rtms-has-sex-dependent-effects-on-the-local-response-of-glia-following-a-penetrating-cortical-stab-injury
#2
Darren Clarke, Marissa A Penrose, Alan R Harvey, Jennifer Rodger, Kristyn A Bates
Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma...
June 14, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622913/targeting-urate-to-reduce-oxidative-stress-in-parkinson-disease
#3
REVIEW
Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622912/clinical-approaches-to-the-development-of-a-neuroprotective-therapy-for-pd
#4
REVIEW
C W Olanow, K Kieburtz, R Katz
The development of a neuroprotective or disease-modifying therapy is the major unmet need in the management of Parkinson's Disease (PD) and the goal of much clinical and scientific research. However, despite enormous efforts and expense, no disease-modifying therapy for PD has been approved to date. Historically attempts to define such a therapy have been limited by confounding symptomatic/pharmacologic effects of the study intervention and the lack of a clear and well-defined regulatory and clinical development pathway that leads to a disease-modifying indication...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28610844/overexpression-of-eif4f-components-in-meningiomas-and-suppression-of-meningioma-cell-growth-by-inhibiting-translation-initiation
#5
REVIEW
Janet L Oblinger, Sarah S Burns, Jie Huang, Li Pan, Yulin Ren, Rulong Shen, A Douglas Kinghorn, D Bradley Welling, Long-Sheng Chang
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation...
June 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28606623/the-interaction-between-alpha-7-nicotinic-acetylcholine-receptor-and-nuclear-peroxisome-proliferator-activated-receptor-%C3%AE-represents-a-new-antinociceptive-signaling-pathway-in-mice
#6
Giulia Donvito, Deniz Bagdas, Wisam Toma, Elnaz Rahimpour, Asti Jackson, Julie A Meade, Shakir AlSharari, Abhijit R Kulkarni, F Ivy Carroll, Aron H Lichtman, Roger L Papke, Ganesh A Thakur, M Imad Damaj
Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca(2+)-dependent manner...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28602834/cns-disease-diminishes-the-therapeutic-functionality-of-bone-marrow-mesenchymal-stem-cells
#7
Alex Sargent, Lianhua Bai, Genevieve Shano, Molly Karl, Eric Garrison, Lahiru Ranasinghe, Sarah M Planchon, Jeffrey Cohen, Robert H Miller
Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28602833/a-novel-il-1ra-pep-fusion-protein-with-enhanced-brain-penetration-ameliorates-cerebral-ischemia-reperfusion-injury-by-inhibition-of-oxidative-stress-and-neuroinflammation
#8
Dong-Dong Zhang, Min-Ji Zou, Ya-Tao Zhang, Wen-Liang Fu, Tao Xu, Jia-Xi Wang, Wen-Rong Xia, Zhi-Guang Huang, Xiang-Dong Gan, Xiao-Ming Zhu, Dong-Gang Xu
Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP)...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28602832/fumarate-decreases-edema-volume-and-improves-functional-outcome-after-experimental-stroke
#9
Bettina Hjelm Clausen, Louise Lundberg, Minna Yli-Karjanmaa, Nellie Anne Martin, Martina Svensson, Maria Zeiler Alfsen, Simon Bertram Flæng, Kristina Lyngsø, Antonio Boza-Serrano, Helle H Nielsen, Pernille B Hansen, Bente Finsen, Tomas Deierborg, Zsolt Illes, Kate Lykke Lambertsen
BACKGROUND: Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl-fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after ischemic stroke in mice. METHODS: Permanent middle cerebral artery occlusion (pMCAO) was performed using adult, male C57BL/6 mice...
June 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28601605/rapid-focal-cooling-attenuates-cortical-seizures-in-a-primate-epilepsy-model
#10
Guoping Ren, Jiaqing Yan, Guoxian Tao, Yunmeng Gan, Donghong Li, Xi Yan, Yongjuan Fu, Leiming Wang, Weimin Wang, Zhiming Zhang, Feng Yue, Xiaofeng Yang
Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys...
June 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28601604/axonal-dystrophy-in-the-brain-of-mice-with-sanfilippo-syndrome
#11
Helen Beard, Sofia Hassiotis, Wei-Ping Gai, Emma Parkinson-Lawrence, John J Hopwood, Kim M Hemsley
Axonal dystrophy has been described as an early pathological feature of neurodegenerative disorders including Alzheimer's disease and amyotrophic lateral sclerosis. Axonal inclusions have also been reported to occur in several neurodegenerative lysosomal storage disorders including Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome). This disorder results from a mutation in the gene encoding the lysosomal sulphatase sulphamidase, and as a consequence heparan sulphate accumulates, accompanied by secondarily-stored gangliosides...
June 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28601603/enhanced-classical-complement-pathway-activation-and-altered-phagocytosis-signaling-molecules-in-human-epilepsy
#12
Season K Wyatt, Thomas Witt, Nicholas M Barbaro, Aaron A Cohen-Gadol, Amy L Brewster
Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about the status of this phenotype in epilepsy. Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy...
June 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587876/strength-of-cholinergic-tone-dictates-the-polarity-of-dopamine-d2-receptor-modulation-of-striatal-cholinergic-interneuron-excitability-in-dyt1-dystonia
#13
Mariangela Scarduzio, Chelsea N Zimmerman, Karen L Jaunarajs, Qin Wang, David G Standaert, Lori L McMahon
Balance between cholinergic and dopaminergic signaling is central to striatal control of movement and cognition. In dystonia, a common disorder of movement, anticholinergic therapy is often beneficial. This observation suggests there is a pathological increase in cholinergic tone, yet direct confirmation is lacking. In DYT1, an early-onset genetic form of dystonia caused by a mutation in the protein torsinA (TorA), the suspected heightened cholinergic tone is commonly attributed to faulty dopamine D2 receptor (D2R) signaling where D2R agonists cause excitation of striatal cholinergic interneurons (ChIs), rather than the normal inhibition of firing observed in wild-type animals, an effect known as "paradoxical excitation"...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587875/the-effectiveness-of-the-anti-cd11d-treatment-is-reduced-in-rat-models-of-spinal-cord-injury-that-produce-significant-levels-of-intraspinal-hemorrhage
#14
N M Geremia, T Hryciw, F Bao, F Streijger, E Okon, J H T Lee, L C Weaver, G A Dekaban, B K Kwon, A Brown
We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587874/neuropathies-in-the-setting-of-neurofibromatosis-tumor-syndromes-complexities-and-opportunities
#15
REVIEW
Alexander Schulz, Peter Grafe, Christian Hagel, Philipp Bäumer, Helen Morrison, Victor-Felix Mautner, Said Farschtschi
The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587873/regulation-of-transient-receptor-potential-cation-channel-subfamily-v1-protein-synthesis-by-the-phosphoinositide-3-kinase-akt-pathway-in-colonic-hypersensitivity
#16
Shanwei Shen, Hamad W Al-Thumairy, Fiza Hashmi, Li-Ya Qiao
The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor 1 (VR1), is expressed in nociceptive neurons in the dorsal root ganglia (DRG) and participates in the transmission of pain. The present study investigated the underlying molecular mechanisms by which TRPV1 was regulated by nerve growth factor (NGF) signaling pathways in colonic hypersensitivity in response to colitis. We found that during colitis TRPV1 protein levels were significantly increased in specifically labeled colonic afferent neurons in both L1 and S1 DRGs...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28587872/validation-of-an-automated-tractography-method-for-the-optic-radiations-as-a-biomarker-of-visual-acuity-in-neurofibromatosis-associated-optic-pathway-glioma
#17
REVIEW
Peter de Blank, Michael J Fisher, Haley Gittleman, Jill S Barnholtz-Sloan, Chaitra Badve, Jeffrey I Berman
INTRODUCTION: Fractional anisotropy (FA) of the optic radiations has been associated with vision deficit in multiple intrinsic brain pathologies including NF1 associated optic pathway glioma, but hand-drawn regions of interest used in previous tractography methods limit consistency of this potential biomarker. We created an automated method to identify white matter tracts in the optic radiations and compared this method to previously reported hand-drawn tractography. METHOD: Automated tractography of the optic radiation using probabilistic streamline fiber tracking between the lateral geniculate nucleus of the thalamus and the occipital cortex was compared to the hand-drawn method between regions of interest posterior to Meyer's loop and anterior to tract branching near the calcarine cortex...
June 3, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#18
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
June 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28579327/manipulating-cognitive-reserve-pre-injury-environmental-conditions-influence-the-severity-of-concussion-symptomology-gene-expression-and-response-to-melatonin-treatment-in-rats
#19
Glenn R Yamakawa, Sabrina Salberg, Karen M Barlow, Brian L Brooks, Michael J Esser, Keith Owen Yeates, Richelle Mychasiuk
In an effort to understand the factors that contribute to heterogeneity in outcomes often associated with mTBI in youth, this study examined the role of premorbid differences in cognitive reserve on post-concussive symptoms (PCS), molecular markers, and treatment response. Male and female rats matured in one of three environmental conditions (Stress, Enrichment, Control), received a mTBI in adolescence, and were randomized to melatonin or placebo treatment. All animals underwent a behavioural test battery designed to examine PCS...
June 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28579325/a-peptide-disrupting-the-d2r-dat-interaction-protects-against-dopamine-neurotoxicity
#20
Ping Su, Fang Liu
Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels...
June 1, 2017: Experimental Neurology
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