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https://www.readbyqxmd.com/read/28432424/variations-of-isovaline-structure-related-to-activity-in-the-formalin-foot-assay-in-mice
#1
Timothy Fung, Yahya I Asiri, Richard Wall, Stephan K W Schwarz, Ernest Puil, Bernard A MacLeod
Current centrally acting analgesics such as opioids are associated with adverse effects that limit their use and threaten patient safety. Isovaline is a novel prototype analgesic that produces peripheral antinociception in several pain models with little or no effect on the central nervous system. The aim of this study was to establish a preliminary structure-activity relationship for isovaline derivatives by assaying efficacy in the formalin foot assay and central adverse effect profile in mice. Selected compounds were tested using the formalin foot assay to determine efficacy in reducing formalin-induced behaviors...
April 21, 2017: Amino Acids
https://www.readbyqxmd.com/read/28421542/neural-stem-cell-transplantation-promotes-functional-recovery-from-traumatic-brain-injury-via-brain-derived-neurotrophic-factor-mediated-neuroplasticity
#2
Liu-Lin Xiong, Yue Hu, Piao Zhang, Zhuo Zhang, Li-Hong Li, Guo-Dong Gao, Xin-Fu Zhou, Ting-Hua Wang
Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10(5)/μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28412607/effect-of-early-postnatal-exposure-to-valproate-on-neurobehavioral-development-and-regional-bdnf-expression-in-two-strains-of-mice
#3
Kevin G Bath, Tiare Pimentel
Valproate has been used for over 30years as a first-line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects...
April 12, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28409389/curcumin-protects-dopaminergic-neurons-against-inflammation-mediated-damage-and-improves-motor-dysfunction-induced-by-single-intranigral-lipopolysaccharide-injection
#4
Neha Sharma, Sheetal Sharma, Bimla Nehru
Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences...
April 13, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28406931/a-model-of-periventricular-leukomalacia-pvl-in-neonate-mice-with-histopathological-and-neurodevelopmental-outcomes-mimicking-human-pvl-in-neonates
#5
Nahla Zaghloul, Hardik Patel, Mohamed Nagy Ahmed
Periventricular leukomalacia (PVL), a brain injury affecting premature infants is commonly associated with cerebral palsy. PVL results from hypoxia-ischemia (HI) with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. It is important to study a PVL mouse model that mimics human PVL in symptomatology, anatomic and molecular basis. In our neonate mice model, bilateral carotid arteries were temporary ligated at P5 followed by hypoxic exposure (FiO2 of 8% for 20 min...
2017: PloS One
https://www.readbyqxmd.com/read/28400118/pre-clinical-therapeutic-development-of-a-series-of-metalloporphyrins-for-parkinson-s-disease
#6
Li-Ping Liang, Jie Huang, Ruth Fulton, Jennifer N Pearson-Smith, Brian J Day, Manisha Patel
Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment...
April 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28392471/expression-of-mutant-disc1-in-purkinje-cells-increases-their-spontaneous-activity-and-impairs-cognitive-and-social-behaviors-in-mice
#7
Alexey V Shevelkin, Chantelle E Terrillion, Bagrat N Abazyan, Tymoteusz J Kajstura, Yan A Jouroukhin, Gay L Rudow, Juan C Troncoso, David J Linden, Mikhail V Pletnikov
In addition to motor function, the cerebellum has been implicated in cognitive and social behaviors. Various structural and functional abnormalities of Purkinje cells (PCs) have been observed in schizophrenia and autism. As PCs express the gene Disrupted-In-Schizophrenia-1 (DISC1), and DISC1 variants have been associated with neurodevelopmental disorders, we evaluated the role of DISC1 in cerebellar physiology and associated behaviors using a mouse model of inducible and selective expression of a dominant-negative, C-terminus truncated human DISC1 (mutant DISC1) in PCs...
April 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28391014/neonatal-alcohol-exposure-reduces-number-of-parvalbumin-positive-interneurons-in-the-medial-prefrontal-cortex-and-impairs-passive-avoidance-acquisition-in-mice-deficits-not-rescued-from-exercise
#8
G F Hamilton, I J Hernandez, C P Krebs, P J Bucko, J S Rhodes
Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored...
April 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28386306/a-preclinical-systematic-review-of-ginsenoside-rg1-in-experimental-parkinson-s-disease
#9
REVIEW
Liang Song, Meng-Bei Xu, Xiao-Li Zhou, Dao-Pei Zhang, Shu-Ling Zhang, Guo-Qing Zheng
To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28385189/suppression-of-nk-and-cd8-t-cells-reduces-astrogliosis-but-accelerates-cerebellar-dysfunction-and-shortens-life-span-in-a-mouse-model-of-sandhoff-disease
#10
Elizabeth J White, Bernardo L Trigatti, Suleiman A Igdoura
Sandhoff disease is an inherited lysosomal storage disease, resulting from the deficiency of lysosomal β-hexosaminidase A and B enzyme activity. The Hexb-/- mouse model recapitulates human disease and leads to fatal neurodegeneration and neuroinflammation. IL-15 is important for the proliferation of NK, NK T, and CD8(+) cytotoxic/memory T cells. In order to determine how changes to IL-15-dependent immune cell populations would alter the course of Sandhoff disease in mice, we generated a Hexb-/-Il-15-/- double knockout mouse and used motor behaviour tests, analyzed peripheral blood and brain leukocyte immunophenotypes, cytokine secretion, as well as examined markers of microgliosis, astrogliosis and apoptosis...
May 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28382306/apolipoprotein-e-mimetic-peptide-cn-105-improves-outcomes-in-ischemic-stroke
#11
Tian Ming Tu, Brad J Kolls, Erik J Soderblom, Viviana Cantillana, Paul Durham Ferrell, M Arthur Moseley, Haichen Wang, Hana N Dawson, Daniel T Laskowitz
OBJECTIVE: At present, the absence of a pharmacological neuroprotectant represents an important unmet clinical need in the treatment of ischemic and traumatic brain injury. Recent evidence suggests that administration of apolipoprotein E mimetic therapies represent a viable therapeutic strategy in this setting. We investigate the neuroprotective and anti-inflammatory properties of the apolipoprotein E mimetic pentapeptide, CN-105, in a microglial cell line and murine model of ischemic stroke...
April 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28372935/synthesis-and-biological-activity-of-novel-tert-amylphenoxyalkyl-homo-piperidine-derivatives-as-histamine-h3r-ligands
#12
Kamil J Kuder, Dorota Łażewska, Maria Kaleta, Gniewomir Latacz, Tim Kottke, Agnieszka Olejarz, Tadeusz Karcz, Andrzej Fruziński, Katarzyna Szczepańska, Janina Karolak-Wojciechowska, Holger Stark, Katarzyna Kieć-Kononowicz
As a continuation of our search for novel histamine H3 receptor ligands a series of twenty new tert-amyl phenoxyalkylamine derivatives (2-21) was synthesized. Compounds of four to eight carbon atoms spacer alkyl chain were evaluated on their binding properties at human histamine H3 receptor (hH3R). The highest affinities were observed for pentyl derivatives 6-8 (Ki=8.8-23.4nM range) and among them piperidine derivative 6 with Ki=8.8nM. Structures 6, 7 were also classified as antagonists in cAMP accumulation assay (with EC50=157 and 164nM, respectively)...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28360444/nepeta-dschuparensis-bornm-extract-moderates-cox-2-and-il-1%C3%AE-proteins-in-a-rat-model-of-cerebral-ischemia
#13
Alireza Mousavi Nia, Taj Pari Kalantaripour, Mohsen Basiri, Farzaneh Vafaee, Majid Asadi-Shekaari, Azam Eslami, Fatemeh Darvish Zadeh
BACKGROUND: Nepeta dschuparensis Bornm (NP) is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. METHODS: Twenty-six male rats were randomly divided into 3 groups: 1) sham (n=6): no middle cerebral artery occlusion (MCAO) procedure, 2) control (n=10): MCAO procedure and treatment with normal saline, and 3) NP extract (n=10): MCAO procedure and treatment with the NP extract (20 mg/kg, i...
March 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28355345/chronic-dosing-with-mirtazapine-does-not-produce-sedation-in-rats
#14
Alberto Salazar-Juárez, Susana Barbosa-Méndez, Paola Merino-Reyes, Maura Matus-Ortega, Jorge A Hernández-Calderón, Benito Antón
OBJECTIVE: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used...
March 23, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28338593/clinical-correlates-to-assist-with-cte-diagnosis-insights-from-a-novel-rodent-repeat-concussion-model
#15
Gretchen M Thomsen, Ara Ko, Megan Y Harada, Annie Ma, Livia Wyss, Patricia Haro, Jean-Philippe Vit, Pablo Avalos, Navpreet Dhillon, Noell Cho, Oksana Shelest, Eric J Ley
INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. CTE symptoms include changes in mood, behavior, cognition and motor function, however CTE is only currently diagnosed post-mortem. Using a rat model of recurrent traumatic brain injury (TBI) we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed skull, mild TBI was administered once per week to 35 WT rats, 8 rats received 2 injuries ('2xTBI'), 27 rats received 5 injuries ('5xTBI') and 13 rats were sham controls...
March 23, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28335684/bone-marrow-derived-endothelial-progenitor-cell-treatment-in-a-model-of-lateral-fluid-percussion-injury-in-rats-evaluation-of-acute-and-subacute-outcome-measures
#16
Eugene Park, Katya J Park, Elaine Liu, Rongcai Jiang, Jian-Ning Zhang, Andrew J Baker
Traumatic brain injury (TBI) continues to be a serious healthcare issue while therapies to treat TBI remain elusive. Promising results from the use of endothelial progenitor cells (EPCs) in numerous disease states highlight the pleiotropic capacity of this cell type. We have previously demonstrated that EPC conditioned media reduces axonal degeneration following in vitro OGD insult and concurrently improves white matter and microvascular outcome in vivo following midline fluid percussion injury. In the current study we evaluated the effectiveness of allogeneic endothelial cells derived from rat bone marrow on microvascular recovery and neuronal sparing following lateral fluid percussion injury...
March 23, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28330826/the-influence-of-methamphetamine-on-maternal-behavior-and-development-of-the-pups-during-the-neonatal-period
#17
Mária Ševčíková, Ivana Hrebíčková, Eva Macúchová, Romana Šlamberová
Since it enters breast milk, methamphetamine (MA) abuse during lactation can not only affect the quality of maternal behavior but also postnatal development of pups. The aim of the present study was to examine the effect of injected MA (5mg/kg) on maternal behavior of rats and the differences in postnatal development, during postnatal days (PD) 1-11, of pups when the pups were directly exposed (i.e., injected) to MA or received MA indirectly via breast milk. Maternal behavior was examined using observation test (PD 1-22) and pup retrieval test (PD 1-12)...
March 19, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28329224/a-clinically-relevant-frailty-index-for-aging-rats
#18
Marshall G Miller, Nopporn Thangthaeng, Barbara Shukitt-Hale
Frailty is a clinical syndrome that is increasingly prevalent during aging. Frailty involves the confluence of reduced strength, speed, physical activity, and endurance and is associated with adverse health outcomes. The present study adapts existing clinical and preclinical indices of frailty to the Fischer (F344) rat. Male F344 rats (n = 133; 17 mo) completed a battery of behavioral tasks, including forelimb wire suspension (strength), rotarod (speed), open field (physical activity), and inclined screen (endurance)...
January 21, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28326933/attenuation-of-hyperalgesia-responses-via-the-modulation-of-5-hydroxytryptamine-signalings-in-the-rostral-ventromedial-medulla-and-spinal-cord-in-a-6-hydroxydopamine-induced-rat-model-of-parkinson-s-disease
#19
Chen-Tao Wang, Cheng-Jie Mao, Xiao-Qi Zhang, Cai-Yi Zhang, Dong-Jun Lv, Ya-Ping Yang, Kai-Lin Xia, Jun-Yi Liu, Fen Wang, Li-Fang Hu, Guang-Yin Xu, Chun-Feng Liu
Background Although pain is one of the most distressing non-motor symptoms among patients with Parkinson's disease, the underlying mechanisms of pain in Parkinson's disease remain elusive. The aim of the present study was to investigate the role of serotonin (5-hydroxytryptamine) in the rostral ventromedial medulla (RVM) and spinal cord in pain sensory abnormalities in a 6-hydroxydopamine-treated rat model of Parkinson's disease. Methods The rotarod test was used to evaluate motor function. The radiant heat test and von Frey test were conducted to evaluate thermal and mechanical pain thresholds, respectively...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326165/neurochemical-and-motor-changes-in-mice-with-combined-mutations-linked-to-parkinson-s-disease
#20
Xiang Bai, Margaret Chia-Ying Wey, Paul Anthony Martinez, Chao Shi, Elizabeth Fernandez, Randy Strong
Considerable evidence suggests that oxidative stress plays a role in the pathogenesis of Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder. Reduced expression of aldehyde dehydrogenase-1 (ALDH1) and glutathione peroxidase-1 (GPX1), enzymes that function to detoxify aldehydes and hydroxyl radicals, respectively, has been reported in the substantia nigra of patients who died with PD. To determine whether deficiency in these two genes contributes to the pathogenesis of PD, mice were generated with homozygous null mutations of both Aldh1a1 (the murine homolog of ALDH1) and Gpx1 genes [knockout (KO) mice]...
2017: Pathobiology of Aging & Age related Diseases
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