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Ketamine brain damage

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https://www.readbyqxmd.com/read/29030243/the-inhibition-of-the-kynurenine-pathway-prevents-behavioral-disturbances-and-oxidative-stress-in-the-brain-of-adult-rats-subjected-to-an-animal-model-of-schizophrenia
#1
Gislaine Z Réus, Indianara R T Becker, Giselli Scaini, Fabricia Petronilho, Jean P Oses, Rima Kaddurah-Daouk, Luciane B Ceretta, Alexandra I Zugno, Felipe Dal-Pizzol, João Quevedo, Tatiana Barichello
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
October 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28988615/mechanism-of-synergistic-action-on-behavior-oxidative-stress-and-inflammation-following-co-treatment-with-ketamine-and-different-antidepressant-classes
#2
Gislaine Z Réus, Beatriz I Matias, Amanda L Maciel, Helena M Abelaira, Zuleide M Ignácio, Airam B de Moura, Danyela Matos, Lucineia G Danielski, Fabricia Petronilho, André F Carvalho, João Quevedo
BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist...
May 6, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28840469/early-exposure-to-ketamine-impairs-axonal-pruning-in-developing-mouse-hippocampus
#3
Aleksandar Lj Obradovic, Navya Atluri, Lorenza Dalla Massara, Azra Oklopcic, Nikola S Todorovic, Gaurav Katta, Hari P Osuru, Vesna Jevtovic-Todorovic
Mounting evidence suggests that prolonged exposure to general anesthesia (GA) during brain synaptogenesis damages the immature neurons and results in long-term neurocognitive impairments. Importantly, synaptogenesis relies on timely axon pruning to select axons that participate in active neural circuit formation. This process is in part dependent on proper homeostasis of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF). We set out to examine how GA may modulate axon maintenance and pruning and focused on the role of BDNF...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28687197/opioid-receptor-activation-is-involved-in-neuroprotection-induced-by-trpv1-channel-activation-against-excitotoxicity-in-the-rat-retina
#4
Kenji Sakamoto, Taiyo Kuroki, Tomonori Sagawa, Hiroko Ito, Asami Mori, Tsutomu Nakahara, Kunio Ishii
Recently, we reported that capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, protected against excitotoxicity induced by intravitreal N-methyl-D-aspartic acid (NMDA) in the rats in vivo. It has been reported that morphine, an opioid receptor agonist, ameliorated excitotoxicity induced by ischemia-reperfusion in the retina, and that capsaicin-induced neuroprotection was reduced by naloxone, an opioid receptor antagonist in the brain. The aim of the present study is to clarify whether activation of opioid receptors is involved in the capsaicin-induced neuroprotection in the retina...
July 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433652/ketamine-potentiates-oxidative-stress-and-influences-behavior-and-inflammation-in-response-to-lipolysaccharide-lps-exposure-in-early-life
#5
Gislaine Z Réus, Lutiana R Simões, Gabriela D Colpo, Giselli Scaini, Jean P Oses, Jaqueline S Generoso, Alan R Prossin, Rima Kaddurah-Daouk, João Quevedo, Tatiana Barichello
Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, levels of cytokines, and the locomotor activity of IA in a schizophrenia animal model in which neonatal male Wistar rats were administered with an injection of LPS (50μg/kg) on postnatal day 3 and different doses of ketamine (5, 15 and 25mg/kg) for 7days during adulthood...
April 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28391017/pretreatment-with-minocycline-restores-neurogenesis-in-the-subventricular-zone-and-subgranular-zone-of-the-hippocampus-after-ketamine-exposure-in-neonatal-rats
#6
Yang Lu, P K Giri, Shan Lei, Juan Zheng, Weisong Li, Ning Wang, Xinlin Chen, Haixia Lu, Zhiyi Zuo, Yong Liu, Pengbo Zhang
Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28286284/pre-clinical-investigation-of-diabetes-mellitus-as-a-risk-factor-for-schizophrenia
#7
Alexandra S Almeida Heylmann, Lara Canever, Katia Gress, Sarah T Gomes, Isadora Fachim, Carolina Michels, Geórgia C Stopassoli, Gustavo A Mastella, Amanda V Steckert, Adriani P Damiani, Vanessa M de Andrade, João Quevedo, Alexandra I Zugno
This study investigated the behavioral and biochemical parameters of DM1 as a risk factor in an animal model of schizophrenia (SZ). All groups: 1 Control (saline+saline); 2 Alloxan (alloxan+saline); 3 Ketamine (saline+ketamine); 4 (Alloxan+Ketamine) were fasted for a period of 18h before the subsequent induction of DM via a single intraperitoneal (i.p) injection of alloxan (150mg/kg). From the 4th to the 10th days, the animals were injected i.p with ketamine (25mg/kg) or saline, once a day, to induce a model of SZ and 30min after the last administration were subjected to behavioral testing...
March 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27981535/remote-ischemic-preconditioning-provides-neuroprotection-impact-on-ketamine-induced-neuroapoptosis-in-the-developing-rat-brain
#8
W Ma, Y-Y Cao, S Qu, S-S Ma, J-Z Wang, L-Q Deng, W-J Yuan, J-H Meng
OBJECTIVE: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. MATERIALS AND METHODS: To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27914827/inhibition-of-long-non-coding-rna-igf2as-protects-apoptosis-and-neuronal-loss-in-anesthetic-damaged-mouse-neural-stem-cell-derived-neurons
#9
Chengwei Song, Chengjun Song, Kui Chen, Xiangdong Zhang
BACKGROUND: In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells. METHODS: Murine E18.5 brain-derived neural stem cells were cultured in vitro. During neural differentiation stage, ketamine-induced gene expression changes of IGF2 and IGF2AS were recorded by qRT-PCR...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27769874/preventive-effects-of-blueberry-extract-on-behavioral-and-biochemical-dysfunctions-in-rats-submitted-to-a-model-of-manic-behavior-induced-by-ketamine
#10
Gabriela Debom, Marta Gazal, Mayara Sandrielly Pereira Soares, Carlus Augustu Tavares do Couto, Bruna Mattos, Claiton Lencina, Manuella Pinto Kaster, Gabriele Codenonzi Ghisleni, Rejane Tavares, Elizandra Braganhol, Vitor Clasen Chaves, Flávio Henrique Reginatto, Francieli Stefanello, Roselia Maria Spanevello
The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus...
October 18, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27590136/ketamine-exhibits-different-neuroanatomical-profile-after-mammalian-target-of-rapamycin-inhibition-in-the-prefrontal-cortex-the-role-of-inflammation-and-oxidative-stress
#11
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Lucineia G Danielski, Fabricia Petronilho, André F Carvalho, João Quevedo
Studies indicated that mammalian target of rapamycin (mTOR), oxidative stress, and inflammation are involved in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been identified as a novel MDD therapy; however, the antidepressant mechanism is not fully understood. In addition, the effects of ketamine after mTOR inhibition have not been fully investigated. In the present study, we examined the behavioral and biochemical effects of ketamine in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens after inhibition of mTOR signaling in the PFC...
September 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27443555/reactive-oxygen-species-mediated-loss-of-phenotype-of-parvalbumin-interneurons-contributes-to-long-term-cognitive-impairments-after-repeated-neonatal-ketamine-exposures
#12
Hui Zhang, Xiao-Ru Sun, Jing Wang, Zhen-Zhen Zhang, Hong-Ting Zhao, Hui-Hui Li, Mu-Huo Ji, Kuan-Yu Li, Jian-Jun Yang
Ketamine, a common anesthetic used for pediatric patients, has been shown to induce neurotoxicity and alter adolescent behaviors in rats when administered during neonatal period. However, the mechanisms underlying this kind of neurotoxicity remain largely to be determined. Herein, we studied whether the reactive oxygen species (ROS) due to the increased NOX2 mediates loss of phenotype of PV interneurons and thus contributes to long-term cognitive impairments after repeated ketamine exposures. Sprague-Dawley male rat pups received a daily administration of ketamine intraperitoneally (75 mg/kg) from postnatal day 6 (P6) to P8 for three consecutive days...
November 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27367209/effect-of-folic-acid-on-oxidative-stress-and-behavioral-changes-in-the-animal-model-of-schizophrenia-induced-by-ketamine
#13
Alexandra I Zugno, Lara Canever, Alexandra S Heylmann, Patrícia G Wessler, Amanda Steckert, Gustavo A Mastella, Mariana B de Oliveira, Louyse S Damázio, Felipe D Pacheco, Octacílio P Calixto, Flávio P Pereira, Tamires P Macan, Thayara H Pedro, Patrícia F Schuck, João Quevedo, Josiane Budni
Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid...
October 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27329284/evaluation-of-acetylcholine-seizure-activity-and-neuropathology-following-high-dose-nerve-agent-exposure-and-delayed-neuroprotective-treatment-drugs-in-freely-moving-rats
#14
Cindy Acon-Chen, Jeffrey A Koenig, Garrett R Smith, Amber R Truitt, Thaddeus P Thomas, Tsung-Ming Shih
Organophosphorus nerve agents such as soman (GD) inhibit acetylcholinesterase, producing an excess of acetylcholine (ACh), which results in respiratory distress, convulsions and status epilepticus that leads to neuropathology. Several drugs (topiramate, clobazam, pregnanolone, allopregnanolone, UBP 302, cyclopentyladenosine [CPA], ketamine, midazolam and scopolamine) have been identified as potential neuroprotectants that may terminate seizures and reduce brain damage. To systematically evaluate their efficacy, this study employed in vivo striatal microdialysis and liquid chromatography to respectively collect and analyze extracellular ACh in freely moving rats treated with these drugs 20 min after seizure onset induced by a high dose of GD...
June 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27250524/neuroprotective-effects-of-the-ethanol-stem-bark-extracts-of-terminalia-ivorensis-in-ketamine-induced-schizophrenia-like-behaviors-and-oxidative-damage-in-mice
#15
Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Abayomi Mayowa Ajayi, Ezekiel Oluwagbenga Iwalewa
CONTEXT: Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice. OBJECTIVE: This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice...
December 2016: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27165402/bdnf-erk1-2-signaling-pathway-in-ketamine-associated-lower-urinary-tract-symptoms
#16
Xiaolong Wang, Biwen Peng, Chang Xu, Zhengyan Gao, Yuanfei Cao, Zhao Liu, Tongzu Liu
OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment. METHODS: Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group...
September 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27132109/relationship-between-ketamine-induced-developmental-neurotoxicity-and-nmda-receptor-mediated-calcium-influx-in-neural-stem-cell-derived-neurons
#17
Cheng Wang, Fang Liu, Tucker A Patterson, Merle G Paule, William Slikker
Ketamine, a noncompetitive NMDA receptor antagonist, is used as a general anesthetic and recent data suggest that general anesthetics can cause neuronal damage when exposure occurs during early brain development. To elucidate the underlying mechanisms associated with ketamine-induced neurotoxicity, stem cell-derived models, such as rodent neural stem cells harvested from rat fetuses and/or neural stem cells derived from human induced pluripotent stem cells (iPSC) can be utilized. Prolonged exposure of rodent neural stem cells to clinically-relevant concentrations of ketamine resulted in elevated NMDA receptor levels as indicated by NR1subunit over-expression in neurons...
April 27, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27033443/ketamine-decreases-inflammatory-and-immune-pathways-after-transient-hypoxia-in-late-gestation-fetal-cerebral-cortex
#18
Eileen I Chang, Miguel A Zárate, Maria B Rabaglino, Elaine M Richards, Thomas J Arndt, Maureen Keller-Wood, Charles E Wood
Transient hypoxia in pregnancy stimulates a physiological reflex response that redistributes blood flow and defends oxygen delivery to the fetal brain. We designed the present experiment to test the hypotheses that transient hypoxia produces damage of the cerebral cortex and that ketamine, an antagonist ofNMDAreceptors and a known anti-inflammatory agent, reduces the damage. Late gestation, chronically catheterized fetal sheep were subjected to a 30-min period of ventilatory hypoxia that decreased fetal PaO2from 17 ± 1 to 10 ± 1 mmHg, or normoxia (PaO217 ± 1 mmHg), with or without pretreatment (10 min before hypoxia/normoxia) with ketamine (3 mg/kg, i...
March 2016: Physiological Reports
https://www.readbyqxmd.com/read/26813465/mechanisms-of-propofol-attenuation-of-ketamine-induced-neonatal-brain-injury
#19
C-H Zhao, G-H Li, Q Wang, B Zhao, Z-B Wang
OBJECTIVE: We studied the mechanisms of protective effects of propofol on ketamine-induced damage to neonatal cognitive function. MATERIALS AND METHODS: We utilized a rat model of ketamine anaesthesia. Eighty neonatal rats (7 days after birth) were divided into four groups: normal saline group, ketamine group, and low- and high-dose propofol combined with ketamine groups. Six hours after anaesthesia, we obtained hippocampal tissue, and quantified apoptotic index and total protein concentration, and assessed global proteomics changes induced by two tested drugs...
2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/26476838/anesthetic-ketamine-induced-dna-damage-in-different-cell-types-in-vivo
#20
Daniela Dimer Leffa, Bruno Nunes Bristot, Adriani Paganini Damiani, Gabriela Daminelli Borges, Francine Daumann, Gabriela Maria Zambon, Gabriela Elibio Fagundes, Vanessa Moraes de Andrade
The use of a combination of ketamine and xylazine is broadly used either for anesthesia or euthanasia in rodent animal models in research. However, the genotoxicity and mutagenic effects of these drugs are unknown. Therefore, the aim of this study was to evaluate these effects to help the understanding of elevated values in negative controls in genotoxic/mutagenic assays. Sixty CF-1 mice were divided into ten groups of six mice per group: negative control (saline), positive control (doxorubicin, 40 mg/kg), ketamine at 80 mg/kg and xylazine at 10 mg/kg, ketamine at 100 mg/kg and xylazine at 10 mg/kg, ketamine at 140 mg/kg and xylazine at 8 mg/kg, ketamine at 80 mg/kg, ketamine at 100 mg/kg, ketamine at 140 mg/kg, xylazine at 8 mg/kg, and xylazine at 10 mg/kg...
October 2016: Molecular Neurobiology
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