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Maud Pétrault, Sophie Gautier, Vincent Bérézowski, Thavarak Ouk, Michèle Bastide, Olivier Pétrault, Régis Bordet
Analgesics such as opioid agonists are usually not given during the post-operative phase of experimental stroke because they are susceptible to interfere with the evaluation of neuroprotective therapies. Here we investigate the potential of acetaminophen and nefopam, two non-opioid analgesic drugs, to exert an analgesic effect without inducing neuroprotection in a murine model of ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a significant decrease in the infarct volume, particularly in the cortex (VEHICLE: 200...
September 30, 2016: Fundamental & Clinical Pharmacology
Emilia Grzęda, Eberhard Schlicker, Marek Toczek, Iwona Zalewska, Marta Baranowska-Kuczko, Barbara Malinowska
We have shown previously that the cannabinoid receptor agonist CP55940 microinjected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anaesthetized rats induces depressor and pressor cardiovascular effects in the absence and presence of the CB1 antagonist AM251, respectively. The aim of our study was to examine whether the hypotension and/or hypertension induced by CP55940 given into the PVN results from its influence on glutamatergic and GABAergic neurotransmission. CP55940 was microinjected into the PVN of urethane-anaesthetized rats twice (S1 and S2, 20 min apart)...
September 22, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Qingqing Qi, Feixue Chen, Wenxue Zhang, Peng Wang, Yanqing Li, Xiuli Zuo
BACKGROUND AND AIMS: N-methyl-D-aspartate receptor (NMDAR) in brain, spinal cord and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS). METHODS: The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and western blot, and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire...
August 30, 2016: Journal of Gastroenterology and Hepatology
Kh Reeta, Pankaj Prabhakar, Yogendra K Gupta
Treatment of depression, a common comorbidity in patients with epilepsy, is restricted as certain antidepressants are considered to be proconvulsants. In contrast, anticonvulsant effects have been reported with some antidepressants. In the present study, the effect of tianeptine, an antidepressant, was evaluated against pentylenetetrazole (PTZ)-induced seizures, cognitive impairment and oxidative stress in rats. Tianeptine was administered in three doses (20, 40 and 80 mg/kg) 30 min before PTZ (60 mg/kg, intraperitoneally)...
October 2016: Behavioural Pharmacology
Nawab John Dar, Javeed Ahmad Bhat, Naresh Kumar Satti, Parduman Raj Sharma, Abid Hamid, Muzamil Ahmad
Withania somnifera has immense pharmacologic and clinical uses. Owing to its similar pharmacologic activity as that of Korean Ginseng tea, it is popularly called as Indian ginseng. In most cases, extracts of this plant have been evaluated against various diseases or models of disease. However, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to evaluate Withanone, one of the active constituents of Withania somnifera against NMDA-induced excitotoxicity in retinoic acid, differentiated Neuro2a cells...
August 19, 2016: Molecular Neurobiology
Kurt-Wolfram Sühs, Viktoria Gudi, Nils Eckermann, Richard Fairless, Refik Pul, Thomas Skripuletz, Martin Stangel
The N-methyl-d-aspartate receptor (NMDA-R) is crucial for synaptic transmission and plasticity. Over-activation, as well as complete blockade, of receptor function can lead to severe impairment. However, modest modulation of the receptor has been reported to be neuroprotective via endogenous regulation of the receptor and its subunit composition in response to pathophysiological conditions. As an important model for de- and remyelination in the central nervous system (CNS) we examined NMDA-R regulation in the mouse cuprizone model...
August 26, 2016: Neuroscience Letters
Corinna Roschlau, Angeline Votteler, Wolfgang Hauber
Here we tested in rats effects of the procognitive drugs modafinil and methylphenidate on post-acquisition performance in an object-location paired-associates learning (PAL) task. Modafinil (32; 64 mg/kg) was without effect, while higher (9 mg/kg) but not lower (4.5 mg/kg) doses of methylphenidate impaired PAL performance. Likewise, higher but not lower doses of amphetamine (0.4; 0.8 mg/kg) and MK-801 (0.08; 0.12 mg/kg) decreased PAL performance. Impaired PAL performance induced by methylphenidate, amphetamine, and MK801 most likely reflects compromised cognitive function, e...
August 2016: Learning & Memory
Yasushi Hasegawa, Tatsuro Inoue, Satoshi Kawaminami, Miho Fujita
OBJECTIVE: To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). METHODS: Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. RESULTS: Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test...
July 2016: Asian Pacific Journal of Tropical Medicine
Zhen-Zhen Duan, Feng Zhang, Feng-Ying Li, Yi-Fei Luan, Peng Guo, Yi-Hang Li, Yong Liu, Su-Hua Qi
It has been demonstrated that Src could modulate NMDA receptor, and PAR1 could also affect NMDAR signaling. However, whether PAR1 could regulate NMDAR through Src under ICH has not yet been investigated. In this study, we demonstrated the role of Src-PSD95-GluN2A signaling cascades in rat ICH model and in vitro thrombin challenged model. Using the PAR1 agonist SFLLR, antagonist RLLFS and Src inhibitor PP2, electrophysiological analysis showed that PAR1 regulated NMDA-induced whole-cell currents (INMDA) though Src in primary cultured neurons...
2016: Scientific Reports
Eunkyung Lee, So-Young Choi, Jae-Ho Yang, Youn Ju Lee
Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC)...
July 2016: Korean Journal of Physiology & Pharmacology
William M Armstead, John Riley, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines
BACKGROUND AND PURPOSE: The sole Food and Drug Administration-approved treatment for stroke is tissue-type plasminogen activator (tPA), but its brief therapeutic window and complications of treatment constrain its use. One limitation may be its potential to exacerbate impairment of cerebral autoregulation after stroke. Vasodilation is maintained by elevations in cAMP. However, cAMP levels fall after stroke because of overactivation of N-methyl-d-aspartate receptors by toxic levels of glutamate, an effect that is exacerbated by tPA...
August 2016: Stroke; a Journal of Cerebral Circulation
Xian-Qing Ren, Rong Ma, Chang-Quan Yang, Quan-Hui Liu, Ju Jiao, Xi-Lian Zhang, Ping Rong
PURPOSE: To investigate the effects and mechanisms of Kangxian (KX) capsules on hippocampal neuron convulsive injuries. METHODS: An epileptic discharge model was prepared with hippocampal neurons and divided into groups that were subjected to control, Mg-free, MK801, or anti-epilepsy (KX) interventions for 6 or 24h. The N-methyl-d-aspartate (NMDA) receptor channel current was recorded with a whole-cell patch-clamp technique, and the decay tau was determined from the receptor channel attenuation...
August 2016: Seizure: the Journal of the British Epilepsy Association
Seira Doi, Tomohisa Mori, Naoki Uzawa, Takamichi Arima, Tomoyuki Takahashi, Masashi Uchida, Ayaka Yawata, Michiko Narita, Yasuhito Uezono, Tsutomu Suzuki, Minoru Narita
BACKGROUND: Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment...
2016: Molecular Pain
Andréia S Cunha, Filipe C Matheus, Morgana Moretti, Tuane B Sampaio, Anicleto Poli, Danúbia B Santos, Dirleise Colle, Mauricio P Cunha, Carlos H Blum-Silva, Louis P Sandjo, Flávio H Reginatto, Ana Lúcia S Rodrigues, Marcelo Farina, Rui D Prediger
Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i...
October 1, 2016: Behavioural Brain Research
Yuniesky Andrade-Talavera, Paloma Duque-Feria, Ole Paulsen, Antonio Rodríguez-Moreno
Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t-LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12-P18) mouse hippocampus...
August 2016: Cerebral Cortex
Yumi Takemoto
Elevated L-homocysteine concentrations in the plasma and cerebrospinal fluid are related to cardiovascular and neuronal diseases, and could contribute to disease development. However, the central cardiovascular actions of L-homocysteine in two important autonomic regulating areas remain unknown: the rostral ventrolateral medulla (RVLM), including pre-sympathetic neurons, and the caudal ventrolateral medulla (CVLM), including interneurons projecting to pre-sympathetic neurons in the RVLM. Therefore, the aim of the current study was to examine the influence of L-homocysteine microinjected into the RVLM and CVLM areas on changes in arterial blood pressure (ABP) and heart rate (HR) of anesthetized rats, as well as the influence of ionotropic excitatory amino acid (iEAA) receptors on the central actions of L-homocysteine...
September 2016: Amino Acids
Mari Sild, Marion R Van Horn, Anne Schohl, Dantong Jia, Edward S Ruthazer
UNLABELLED: Radial glia in the developing optic tectum extend highly dynamic filopodial protrusions within the tectal neuropil, the motility of which has previously been shown to be sensitive to neural activity and nitric oxide (NO) release. Using in vivo two-photon microscopy, we performed time-lapse imaging of radial glial cells and measured filopodial motility in the intact albino Xenopus laevis tadpole. Application of MK801 to block neuronal NMDA receptor (NMDAR) currents confirmed a significant reduction in radial glial filopodial motility...
May 11, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zhen Li, Fang Fang, Yuanyin Wang, Liecheng Wang
Ischemic stroke is a primary cause of mortality and disability in the aged population. Resveratrol (Res), a natural polyphenol enriched in plants, presents diverse biological activities, e.g., antiinflammatory and anti-oxidation effects. Here, we evaluated whether Res pretreatment influenced focal cerebral ischemia-induced cognitive impairment, and we explored the underlying mechanisms in rats. The results showed that a single administration of Res (30mg/kg, i.p.) at 1 or 4h, but not at 24h before focal cerebral ischemia exerted significant neuroprotective effects, including a reduction in hippocampal CA1 neuronal death and spatial cognition deficits caused by ischemia...
July 2016: Pharmacology, Biochemistry, and Behavior
Cunyan Li, Yamei Tang, Jingjing Yang, Xianghui Zhang, Yong Liu, Aiguo Tang
It has been reported that specific environmental influences during the postpartum period might contribute to the development of schizophrenia (SZ). Administration of MK801 during early development led to persistent brain pathology. Glutamate decarboxylase 1 (GAD67) and parvalbumin (PV), and neuregulin 1 (NRG1)/ErbB4 signaling were closely associated with SZ pathology. We postulated therefore that NMDA receptor antagonists exposure during the postpartum period may be associated with expression dysregulation of some of the SZ candidate proteins...
August 2016: Neurochemical Research
Xue Wen Wei, Ling Yun Hao, Su Hua Qi
S-nitrosylation, the nitric oxide-derived post-translational modification of proteins, plays critical roles in various physiological and pathological functions. In this present study, a rat model of cerebral ischemia and reperfusion by four-vessel occlusion was generated to assess MKK4 S-nitrosylation. Immunoprecipitation and immunoblotting were performed to evaluate MKK4 S-nitrosylation and phosphorylation. Neuronal loss was observed using histological detection. These results indicated that endogenous NO promoted the S-nitrosylation of MKK4...
June 2016: Brain Research Bulletin
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