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https://www.readbyqxmd.com/read/29653188/ketamine-reduces-deleterious-consequences-of-spreading-depolarizations
#1
Katelyn M Reinhart, C William Shuttleworth
Recent work has implicated spreading depolarization (SD) as a key contributor the progression of acute brain injuries, however development of interventions selectively targeting SDs has lagged behind. Initial clinical intervention efforts have focused on observations that relatively high doses of the sedative agent ketamine can completely suppress SD. However blocking propagation of SD could theoretically prevent beneficial effects of SD in surrounding brain regions. Selective targeting of deleterious consequences of SD (rather than abolition) could be a useful adjunct approach, and be achieved with lower ketamine concentrations...
April 10, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29607941/gyy4137-an-extended-release-hydrogen-sulfide-donor-reduces-nmda-induced-neuronal-injury-in-the-murine-retina
#2
Kohei Sone, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara
We previously reported that systemic administration with sodium hydrogen sulfide, a rapid-release donor compound of hydrogen sulfide (H2 S), protected retinal neurons against N-methyl-D-aspartic acid (NMDA)-induced injury. For clinical application of H2 S donors for retinal neurodegeneration, topical administration with an extended-release donor compound will be better. In the present study, we histologically investigated whether GYY4137, an extended-release hydrogen sulfide donor, had a protective effect on NMDA-induced retinal injury in the mice in vivo...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29596995/applying-ketamine-to-alleviate-the-ptsd-like-effects-by-regulating-the-hcn1-related-bdnf
#3
Lanwei Hou, Yirui Qi, Hongwei Sun, Gang Wang, Qi Li, Yanyu Wang, Zuoji Zhang, Zhongde Du, Lin Sun
BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived...
March 26, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29576117/a-neurosteroid-analogue-with-t-type-calcium-channel-blocking-properties-is-an-effective-hypnotic-but-is-not-harmful-to-neonatal-rat-brain
#4
N Atluri, S M Joksimovic, A Oklopcic, D Milanovic, J Klawitter, P Eggan, K Krishnan, D F Covey, S M Todorovic, V Jevtovic-Todorovic
BACKGROUND: More than 4 million children are exposed annually to sedatives and general anaesthetics (GAs) in the USA alone. Recent data suggest that common GAs can be detrimental to brain development causing neurodegeneration and long-term cognitive impairments. Challenged by a recent US Food and Drug Administration (FDA) warning about potentially neurotoxic effects of GAs in children, there is an urgent need to develop safer GAs. METHODS: Postnatal Day 7 (P7) rat pups of both sexes were exposed to six (repeated every 2 h) injections of equipotent hypnotic doses of ketamine or the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) for 12 h...
April 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29570499/ketamine-effects-on-mammalian-target-of-rapamycin-signaling-in-the-mouse-limbic-system-depend-on-functional-dopamine-d3-receptors
#5
Cristiano Chiamulera, Marzia di Chio, Laura Cavalleri, Marco Venniro, Laura Padovani, Ginetta Collo
Ketamine is a noncompetitive glutamate N-methyl-D-aspartic acid receptor antagonist. When acutely administered to rodents, it produces a rapid antidepressant effect. There is evidence that N-methyl-D-aspartic acid receptor blockade enhances glutamatergic transmission preferentially engaging α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leading to mTOR (mammalian target of rapamycin) pathways activation, thus resulting into downstream neuroadaptive changes in limbic structures. Recent in-vitro data on primary neuronal cultures showed that ketamine activates mTOR also in dopaminergic neurons, and this activation depends on the presence of functional dopamine D3 receptors...
March 22, 2018: Neuroreport
https://www.readbyqxmd.com/read/29568261/8-o-acetyl-shanzhiside-methylester-from-lamiophlomis-rotata-reduces-neuropathic-pain-by-inhibiting-the-erk-tnf-%C3%AE-pathway-in-spinal-astrocytes
#6
Wei Zhang, Yang Bai, Yu Qiao, Jian Wang, Meng-Ying Li, Jing-Wen Wang, Na Jia, Tao Chen, Yun-Qing Li, Ai-Dong Wen
Lamiophlomis rotata ( L. rotata ; Benth.) Kudo is an effective traditional herb in the clinical treatment of chronic pain syndromes in China. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in L. rotata , possesses potent immunosuppressive activities and favorable analgesic effects. This study was proposed to compare the analgesic effects of 8-OaS with those of lidocaine and ketamine in a spinal nerve ligation (SNL) model by behavioral tests, and then investigated its effects upon the expression of spinal glial fibrillary acidic protein (GFAP), phosphorylated extracellular regulated protein kinases (pERK) and tumor necrosis factor-alpha (TNF-α) via immunofluorescence staining and western blot analyses...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29560119/hcn-channels-contribute-to-the-sensitivity-of-intravenous-anesthetics-in-developmental-mice
#7
Jie Gao, Zhiqiang Hu, Liwei Shi, Na Li, Yeling Ouyang, Shaofang Shu, Shanglong Yao, Xiangdong Chen
It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29559384/region-specific-expression-of-nmda-receptor-glun2c-subunit-in-parvalbumin-positive-neurons-and-astrocytes-analysis-of-glun2c-expression-using-a-novel-reporter-model
#8
Aparna Ravikrishnan, Pauravi J Gandhi, Gajanan P Shelkar, Jinxu Liu, Ratnamala Pavuluri, Shashank M Dravid
Hypofunction of NMDA receptors in parvalbumin (PV)-positive interneurons has been proposed as a potential mechanism for cortical abnormalities and symptoms in schizophrenia. GluN2C-containing receptors have been linked to this hypothesis due to the higher affinity of psychotomimetic doses of ketamine for GluN1/2C receptors. However, the precise cell-type expression of GluN2C subunit remains unknown. We describe the expression of the GluN2C subunit using a novel EGFP reporter model. We observed EGFP(GluN2C) localization in PV-positive neurons in the nucleus reticularis of the thalamus, globus pallidus externa and interna, ventral pallidum and substantia nigra...
March 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29558629/anticonvulsant-effect-of-minocycline-on-pentylenetetrazole-induced-seizure-in-mice-involvement-of-nitric-oxide-and-n-methyl-d-aspartate-receptor
#9
Hossein Amini-Khoei, Nastaran Kordjazy, Arya Haj-Mirzaian, Shayan Amiri, Arvin Haj-Mirzaian, Armin Shirzadian, Amin Hasanvand, Shima Balali-Dehkordi, Mahsa Hassanipoor, Ahmad Reza Dehpour
Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg)...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29532791/mechanisms-of-ketamine-action-as-an-antidepressant
#10
P Zanos, T D Gould
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects...
March 13, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29525411/can-we-increase-the-speed-and-efficacy-of-antidepressant-treatments-part-ii-glutamatergic-and-rna-interference-strategies
#11
REVIEW
F Artigas, P Celada, A Bortolozzi
In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals...
March 7, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29501685/ketamine-induced-neurotoxicity-blocked-by-n-methyl-d-aspartate-is-mediated-through-activation-of-pkc-erk-pathway-in-developing-hippocampal-neurons
#12
Sufang Jiang, Xuze Li, Wei Jin, Xiaofeng Duan, Lijun Bo, Jiangli Wu, Rui Zhang, Ying Wang, Rongtian Kang, Lining Huang
Ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis...
March 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29486299/phase-amplitude-coupling-and-epileptogenesis-in-an-animal-model-of-mesial-temporal-lobe-epilepsy
#13
Soheila Samiee, Maxime Lévesque, Massimo Avoli, Sylvain Baillet
Polyrhythmic coupling of oscillatory components in electrophysiological signals results from the interactions between neuronal sub-populations within and between cell assemblies. Since the mechanisms underlying epileptic disorders should affect such interactions, abnormal level of cross-frequency coupling is expected to provide a signal marker of epileptogenesis. We measured phase-amplitude coupling (PAC), a form of cross-frequency coupling between neural oscillations, in a rodent model of mesial temporal lobe epilepsy...
February 24, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29482596/baden-prevention-and-reduction-of-incidence-of-postoperative-delirium-trial-pride-a-phase-iv-multicenter-randomized-placebo-controlled-double-blind-clinical-trial-of-ketamine-versus-haloperidol-for-prevention-of-postoperative-delirium
#14
Harriet Riegger, Alexa Hollinger, Burkhardt Seifert, Katharina Toft, Andrea Blum, Tatjana Zehnder, Martin Siegemund
BACKGROUND: Delirium is a neurobehavioural syndrome that frequently develops in the postoperative setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 10 to 80% (Schonauer et al., J Pept Sci. 2017). Delirium was first described more than half a century ago in the cardiac surgery population (Blachy and Starr, Am J Psychiatry 121:371-5, 1964), where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality...
February 26, 2018: Trials
https://www.readbyqxmd.com/read/29446381/ketamine-blocks-bursting-in-the-lateral-habenula-to-rapidly-relieve-depression
#15
Yan Yang, Yihui Cui, Kangning Sang, Yiyan Dong, Zheyi Ni, Shuangshuang Ma, Hailan Hu
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine...
February 14, 2018: Nature
https://www.readbyqxmd.com/read/29427922/psychotomimetic-like-behavioral-effects-of-memantine-in-the-mouse
#16
Nobue Kitanaka, Junichi Kitanaka, F Scott Hall, Yoshiro Kubota, Yumi Mimura, Sayaka Ogura, Yukiya Okada, George R Uhl, Motohiko Takemura
A single administration of mice with memantine (1-amino-3,5-dimethyladamantane), a glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, induced stereotyped behaviors in dose- and time-dependent manners. The predominant behavioral component of the stereotypy was a continuous, exaggerated sniffing which was accompanied by persistent locomotion. In contrast, a psychostimulant methamphetamine (METH) predominantly induced a stereotyped biting and other forms of intense stationary stereotypical behaviors...
April 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29427655/nicotinic-acetylcholine-receptors-are-associated-with-ketamine-induced-neuronal-apoptosis-in-the-developing-rat-retina
#17
Lingqi Gao, Junde Han, Jie Bai, Jing Dong, Sen Zhang, Mazhong Zhang, Jijian Zheng
Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development...
February 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29370396/ketamine-induced-prefrontal-serotonin-release-is-mediated-by-cholinergic-neurons-in-the-pedunculopontine-tegmental-nucleus
#18
Haruko Kinoshita, Naoya Nishitani, Yuma Nagai, Chihiro Andoh, Nozomi Asaoka, Hiroyuki Kawai, Norihiro Shibui, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
Background: Ketamine rapidly elicits antidepressive effects in humans and mice, in which serotonergic activity is involved. Although α4β2 nicotinic acetylcholine receptor (α4β2 nAChR) in the dorsal raphe nucleus (DRN) plays a key role in the ketamine-induced prefrontal serotonin release, the source of cholinergic afferents and its role are unclear. Methods: Prefrontal serotonin levels after ketamine injection were measured by microdialysis in rats. Electrolytic lesion of pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) was made with constant direct current...
January 23, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29365093/ketamine-intervention-limits-pathogen-expansion-in-vitro
#19
German Torres, Christopher L Hoehmann, Joshua A Cuoco, Kyle Hitscherich, Charles Pavia, Michael Hadjiargyrou, Joerg R Leheste
Ketamine is one of several clinically important drugs whose therapeutic efficacy is due in part to their ability to act upon ion channels prevalent in nearly all biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we show that ketamine short-circuits the growth and spatial expansion of three microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia burgdorferi at doses efficient at reducing depression-like behaviors in mouse models of clinical depression. Although our findings do not reveal the mechanism(s) by which ketamine mediates its antifungal and antibacterial effects, we hypothesize that a function of L-glutamate signal transduction is associated with the ability of ketamine to limit pathogen expansion...
January 22, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29359413/effects-of-chronic-ketamine-on-hippocampal-cross-frequency-coupling-implications-for-schizophrenia-pathophysiology
#20
Timothy I Michaels, Lauren L Long, Ian H Stevenson, James J Chrobak, Chi-Ming A Chen
Disrupted neuronal oscillations have been identified as a potentially important biomarker for the perceptual and cognitive symptoms of schizophrenia. Emerging evidences suggest that interactions between different frequency bands, cross-frequency coupling (CFC), serve an important role in integrating sensory and cognitive information and may contribute to disease pathophysiology. In this study, we investigated the effects of 14-day consecutive administration of ketamine (30 mg/kg i.p.) vs. saline on alterations in amplitude and changes in the coupling of low-frequency (0-30 Hz) phase and high-frequency (30-115 Hz) amplitude in the CA1 hippocampus of Long Evans rats...
January 23, 2018: European Journal of Neuroscience
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