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Ketamine brain damage

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
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
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
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 2, 2016: Molecular Neurobiology
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
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
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
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
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
Cheng Wang, Fang Liu, Tucker A Patterson, Merle G Paule, William Slikker 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
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
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
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
Imran Imran, Markus H Hillert, Jochen Klein
The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures...
December 2015: Journal of Neurochemistry
Yao Fang, Xuefeng Wang
Status epilepticus (SE) is an acute and severe illness of the central nervous system, and prolonged SE can lead to brain damage and even death. Ketamine is a noncompetitive antagonist of glutamatergic N-methyl-d-aspartate (NMDA) receptors. During prolonged seizures, the numbers and activities of GABA receptors gradually decrease; thus, the commonly used first-line and second-line antiepileptic drugs gradually fail. Simultaneously, the numbers and activities of glutamatergic NMDA receptors increase, often causing refractory status epilepticus (RSE) and thus providing the possibility of the use of ketamine to treat RSE...
August 2015: Seizure: the Journal of the British Epilepsy Association
Kenji Sakamoto, Aya Mizuta, Kyosuke Fujimura, Yuki Kurauchi, Asami Mori, Tsutomu Nakahara, Kunio Ishii
High-mobility group Box-1 (HMGB1) is known to be released from injured cells and to induce an inflammatory response. Although HMGB1 was reported to mediate ischemia-reperfusion injury of the brain, its role in glutamate excitotoxicity of the retina remains controversial. Here, the authors demonstrated the evidence that HMGB1 is involved in the retinal damage induced by NMDA. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal injection of NMDA (200 nmol/eye) or HMGB1 protein derived from bovines (5-15 μg/eye)...
August 2015: Experimental Eye Research
Stepani Bendel, Dirk Springe, Adriano Pereira, Denis Grandgirard, Stephen L Leib, Alessandro Putzu, Jannis Schlickeiser, Stephan M Jakob, Jukka Takala, Matthias Haenggi
BACKGROUND: Different anesthesia regimes are commonly used in experimental models of cardiac arrest, but the effects of various anesthetics on clinical outcome parameters are unknown. We conducted a study in which we subjected rats to cardiac arrest under medetomidine/ketamine or sevoflurane/fentanyl anesthesia. METHODS: Asystolic cardiac arrest for 8 minutes was induced in 73 rats with a mixture of potassium chloride and esmolol. Daily behavioral and neurological examination included the open field test (OFT), the tape removal test (TRT) and a neurodeficit score (NDS)...
2015: BMC Anesthesiology
Gislaine Z Réus, Anelise S Carlessi, Stephanie E Titus, Helena M Abelaira, Zuleide M Ignácio, Jaine R da Luz, Beatriz I Matias, Livia Bruchchen, Drielly Florentino, Andriele Vieira, Fabricia Petronilho, João Quevedo
Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived+saline; nondeprived+S-ketamine (15 mg/kg); deprived+saline; deprived+S-ketamine (15 mg/kg)...
November 2015: Developmental Neurobiology
T A Juratli, S E Stephan, A E Stephan, S B Sobottka
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and permanent disability and a common and important global problem. The contribution of secondary posttraumatic brain damage to overall disability in TBI is significant, underlining the importance of prompt and comprehensive treatment for affected patients. METHODS: This article focuses on current concepts of prehospital and emergency room management of patients with severe TBI to prevent secondary brain injuries...
February 2015: Der Anaesthesist
Renán Sánchez-Porras, Zelong Zheng, Oliver W Sakowitz
Spreading depolarization (SD) is a wave of almost complete depolarization of the neuronal and glial cells. Nowadays there is sufficient evidence demonstrating its pathophysiological effect in migraine with aura, transient global amnesia, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. In these cases, occurrence of SD has been associated with functional neuronal damage, neuronal necrosis, neurological degeneration, and poor clinical outcome. Animal models show that SD can be modulated by drugs that interfere with its initiation and propagation...
2015: Acta Neurochirurgica. Supplement
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