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Neuroapoptosis

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https://www.readbyqxmd.com/read/27924651/caffeine-combined-with-sedative-anesthetic-drugs-triggers-widespread-neuroapoptosis-in-a-mouse-model-of-prematurity
#1
Omar Hoseá Cabrera, Shawn David O'Connor, Brant Stephen Swiney, Patricia Salinas-Contreras, Francesca Maria Manzella, George Townsend Taylor, Kevin Kiyoshi Noguchi
OBJECTIVES: Caffeine (CAF) and sedative/anesthetic drugs (SADs) are often coadministered to premature infants in the neonatal intensive care unit (NICU). While SAD neurotoxicity in the developing brain is well established, it is not fully clear whether CAF interacts with SADs and whether this interaction is detrimental. Using a mouse model of prematurity, we hypothesized that CAF would increase apoptotic neurotoxicity when coadministered with SADs. METHODS: Postnatal day 3 mice were treated with vehicle or 80 mg/kg CAF prior to challenge with 6 mg/kg midazolam, 40 mg/kg ketamine, or 40 μg/kg fentanyl...
December 7, 2016: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/27918332/isoflurane-impairs-motor-function-recovery-by-increasing-neuroapoptosis-and-degeneration-during-spinal-ischemia-reperfusion-injury-in-rats
#2
Shih-Yuan Fang, Jung-Shun Lee, Jun-Neng Roan, Yu-Chuan Tsai, Chen-Fuh Lam
BACKGROUND: Spinal cord ischemia (SCI) leads to variable degrees of neurologic deficit in patients undergoing major cardiovascular surgery. The effect of intraoperative neuroprotection against SCI and the subsequent ischemia-reperfusion injury is still limited. Because isoflurane is a commonly used anesthetic agent during major operation, and its neuroprotective and neurotoxicity effects have both been discussed, this study aimed to investigate the effect of isoflurane on the spinal cord's functional recovery in a rat model of cord ischemia...
December 1, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27895665/sugammadex-enhanced-neuronal-apoptosis-following-neonatal-sevoflurane-exposure-in-mice
#3
Maiko Satomoto, Zhongliang Sun, Yushi U Adachi, Koshi Makita
In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity...
2016: Anesthesiology Research and Practice
https://www.readbyqxmd.com/read/27826117/neonatal-inhibition-of-na-k-2cl-cotransporter-prevents-ketamine-induced-spatial-learning-and-memory-impairments
#4
Ryan A Stevens, Brandon D Butler, Saurabh S Kokane, Andrew W Womack, Qing Lin
Prolonged ketamine exposure in neonates at anesthetic doses is known to cause long-term impairments of learning and memory. A current theoretical mechanism explains this phenomenon as being neuro-excitotoxicity mediated by compensatory upregulation of N-methyl-d-aspartate receptors (NMDARs), which then initiates widespread neuroapoptosis. Additionally, the excitatory behavior of GABAergic synaptic transmission mediated by GABAA receptors (GABAARs), occurring during the early neuronal development period, is proposed as contributing to the susceptibility of neonatal neurons to ketamine-induced injury...
November 5, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27820974/oroxylin-a-inhibits-h2o2-induced-oxidative-stress-in-pc12-cells
#5
Qinghe Han, Haiyu Wang, Chong Xiao, Ben-Dong Fu, Chong-Tao Du
Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti-inflammatory and antioxidant effects. However, suppression of oxidative stress and neuroapoptosis by oroxylin A is largely uninvestigated. To investigate the protective effects of oroxylin A, PC12 cells were exposed to oroxylin A and hydrogen peroxide solutions and measured. Oroxylin A significantly reduced the levels of intracellular calcium and reactive oxygen species and increased the levels of CAT and Mn/SOD...
November 7, 2016: Natural Product Research
https://www.readbyqxmd.com/read/27682474/sevoflurane-induced-endoplasmic-reticulum-stress-contributes-to-neuroapoptosis-and-bace-1-expression-in-the-developing-brain-the-role-of-eif2%C3%AE
#6
Bin Liu, Junming Xia, Yali Chen, Jun Zhang
Neonatal exposure to volatile anesthetics causes apoptotic neurodegeneration in the developing brain, possibly leading to neurocognitive deficits in adulthood. Endoplasmic reticulum (ER) stress might be associated with sevoflurane (sevo)-induced neuroapoptosis. However, the signaling pathway regulating sevo-induced neuroapoptosis is not understood. We investigated the effects of neonatal sevo exposure on ER signaling pathway activation. Seven-day-old mouse pups were divided into control (C) and sevo (S; 3 % sevo exposure, 6 h) groups...
September 28, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27604310/selective-cerebral-perfusion-prevents-abnormalities-in-glutamate-cycling-and-neuronal-apoptosis-in-a-model-of-infant-deep-hypothermic-circulatory-arrest-and-reperfusion
#7
Masaki Kajimoto, Dolena R Ledee, Aaron K Olson, Nancy G Isern, Isabelle Robillard-Frayne, Christine Des Rosiers, Michael A Portman
Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. We tested the hypothesis that selective cerebral perfusion modulates glucose utilization, and ameliorates abnormalities in glutamate flux, which occur in association with neuroapoptosis during deep hypothermic circulatory arrest...
November 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27588101/astragaloside-iv-protects-new-born-rats-from-anesthesia-induced-apoptosis-in-the-developing-brain
#8
Jian Sun, Xiao-Ling Chen, Jin-Yu Zheng, Jian-Wei Zhou, Zheng-Liang Ma
Exposure to general anesthesia may cause severe neurotoxicity in developing brain due to neuronal apoptosis. Astragaloside IV (AS IV) has antioxidant and antiapoptosis properties; however, its effects on anesthesia-induced neuroapoptosis have not been studied. In the present study, we determined whether AS IV pre-treatment is able to reduce isoflurane exposure-induced neuroapoptosis in rats. New born rats were pre-treated with AS IV or solvent by oral gavage for three days, then exposed to isoflurane. The results showed that pre-treatment of AS IV significantly inhibited isoflurane-induced neural apoptosis in the hippocampus of new born rats, and such protection was accompanied by reduced levels of caspase-3, nuclear factor-κB activation and phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and increased levels of B-cell lymphoma-2, glycogen synthase kinase-3β, Klotho and phosphorylated protein kinase B...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27586008/isoflurane-anesthesia-exacerbates-learning-and-memory-impairment-in-zinc-deficient-app-ps1-transgenic-mice
#9
Chunsheng Feng, Ya Liu, Ye Yuan, Weiwei Cui, Feng Zheng, Yuan Ma, Meihua Piao
Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1...
December 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27572468/naringenin-pre-treatment-inhibits-neuroapoptosis-and-ameliorates-cognitive-impairment-in-rats-exposed-to-isoflurane-anesthesia-by-regulating-the-pi3-akt-pten-signalling-pathway-and-suppressing-nf-%C3%AE%C2%BAb-mediated-inflammation
#10
Fu-Zhou Hua, Jun Ying, Jing Zhang, Xi-Feng Wang, Yan-Hui Hu, Ying-Ping Liang, Qin Liu, Guo-Hai Xu
The volatile anaesthetic isoflurane is one of the most frequently employed general anaesthetics in neonates, children and adults. Accumulating evidence demonstrated that exposure to anaesthetics is associated with widespread neurodegeneration and cognitive impairment. Thus, the identification and development of compounds capable of preventing or reducing these adverse effects is of great clinical importance. For this purpose, the present study aimed to assess the effects of a flavonoid, naringenin, on isoflurane-induced neuroapoptosis and cognitive impairment...
October 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27537919/from-drug-induced-developmental-neuroapoptosis-to-pediatric-anesthetic-neurotoxicity-where-are-we-now
#11
REVIEW
Catherine E Creeley
The fetal and neonatal periods are critical and sensitive periods for neurodevelopment, and involve rapid brain growth in addition to natural programmed cell death (i.e., apoptosis) and synaptic pruning. Apoptosis is an important process for neurodevelopment, preventing redundant, faulty, or unused neurons from cluttering the developing brain. However, animal studies have shown massive neuronal cell death by apoptosis can also be caused by exposure to several classes of drugs, namely gamma-aminobutyric acid (GABA) agonists and N-methyl-d-aspartate (NMDA) antagonists that are commonly used in pediatric anesthesia...
August 16, 2016: Brain Sciences
https://www.readbyqxmd.com/read/27529322/dexmedetomidine-induced-neuroapoptosis-is-dependent-on-its-cumulative-dose
#12
Jia-Ren Liu, Koichi Yuki, Chongwha Baek, Xiao-Hui Han, Sulpicio G Soriano
BACKGROUND: Dexmedetomidine (DEX) has inherent neuroprotective properties that have been attributed to the activation of prosurvival kinases. However, the impact of supraclinical doses of DEX on neuroapoptosis and neuronal viability has not been determined. METHODS: Rat pups and primary neuronal cells were treated with DEX or ketamine (KET) alone or in combination. Neuroapoptosis was measured by cleaved-caspase-3 expression and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining in brain sections...
October 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27498600/neuroprotective-effects-of-caffeic-acid-phenethyl-ester-against-sevoflurane%C3%A2-induced-neuronal-degeneration-in-the-hippocampus-of-neonatal-rats-involve-mapk-and-pi3k-akt-signaling-pathways
#13
Li-Yan Wang, Zhi-Jun Tang, Yu-Zeng Han
Millions of infants and children are exposed to anesthesia every year during medical care. Sevoflurane is a volatile anesthetic that is frequently used for pediatric anesthesia. However, previous reports have suggested that the administration of sevoflurane promotes neurodegeneration, raising concerns regarding the safety of its usage. The present study aimed to investigate caffeic acid phenethyl ester (CAPE) and its protective effect against sevoflurane‑induced neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20 or 40 mg/kg body weight from postnatal day 1 (P1) to P15...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27497882/neuroprotective-effects-of-kaempferide-7-o-4%C3%A2-o-acetylrhamnosyl-3-o-rutinoside-on-cerebral-ischemia-reperfusion-injury-in-rats
#14
Shuaijun Wang, Huali Xu, Ying Xin, Maowei Li, Wenwen Fu, Yuchen Wang, Zeyuan Lu, Xiaofeng Yu, Dayun Sui
In the present study, we aim to evaluate the potential neuroprotective effect and the underlying mechanism of Kaempferide-7-O-(4″-O-acetylrhamnosyl)-3-O-rutinoside (A-F-B) against cerebral I/R injury. Adult male rats were pretreated with A-F-B by intragastric administration once a day for 3 days. One hour after the third day administration, animals were subjected to 2h of transient middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Neurological deficit, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, apoptosis-related proteins and the expression of pro-inflammator cytokines genes were measured...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27270941/ketamine-midazolam-anesthesia-induces-total-inhibition-of-cortical-activity-in-the-brain-of-newborn-rats
#15
Yu A Lebedeva, A V Zakharova, G F Sitdikova, A L Zefirov, R N Khazipov
The effects of general anesthetics ketamine and midazolam, the drugs that cause neuroapoptosis at the early stages of CNS development, on electrical activity of the somatosensory cortex in newborn rats were studied using extracellular recording of local field potentials and action potentials of cortical neurons. Combined administration of ketamine (40 mg/kg) and midazolam (9 mg/kg) induced surgical coma and almost completely suppressed early oscillatory patterns and neuronal firing. These effects persisted over 3 h after injection of the anesthetics...
May 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27222147/dexmedetomidine-attenuates-repeated-propofol-exposure-induced-hippocampal-apoptosis-pi3k-akt-gsk-3%C3%AE-signaling-disruption-and-juvenile-cognitive-deficits-in-neonatal-rats
#16
Yujie Wang, Changyi Wu, Bin Han, Fei Xu, Mingfeng Mao, Xiangyang Guo, Jun Wang
Propofol is one of the most widely used intravenous anesthetics. However, repeated exposure to propofol may cause neurodegeneration in the developing brain. Dexmedetomidine (Dex), an α2 adrenoceptor agonist, has been previously demonstrated to provide neuroprotection against neuroapoptosis and neurocognitive impairments induced by several anesthetics. Thus, the current study aimed to investigate the effect of Dex on neonatal propofol-induced neuroapoptosis and juvenile spatial learning/memory deficits. Propofol (30 mg/kg) was intraperiotoneally administered to 7‑day‑old Sprague Dawley rats (n=75) three times each day at 90 min intervals for seven consecutive days with or without Dex (75 µg/kg) treatment 20 min prior to propofol injection...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27189477/the-fas-ligand-fas-death-receptor-pathways-contribute-to-propofol-induced-apoptosis-and-neuroinflammation-in-the-brain-of-neonatal-rats
#17
Desanka Milanovic, Vesna Pesic, Natasa Loncarevic-Vasiljkovic, Zeljko Pavkovic, Jelena Popic, Selma Kanazir, Vesna Jevtovic-Todorovic, Sabera Ruzdijic
A number of experimental studies have reported that exposure to common, clinically used anesthetics induce extensive neuroapoptosis and cognitive impairment when applied to young rodents, up to 2 weeks old, in phase of rapid synaptogenesis. Propofol is the most used general anesthetic in clinical practice whose mechanisms of neurotoxicity on the developing brain remains to be examined in depth. This study investigated effects of different exposures to propofol anesthesia on Fas receptor and Fas ligand expressions, which mediate proapoptotic and proinflammation signaling in the brain...
October 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27121046/rno-mir-665-targets-bcl2l1-bcl-xl-and-increases-vulnerability-to-propofol-in-developing-astrocytes
#18
Wen-Chong Sun, Ling Pei
Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno-miR-665 regulation. However, the role of rno-miR-665 during the growth spurt of neonatal rodent brains in vivo is still uncertain. Post-natal day 7 (P7) rats received a single injection of propofol 30 mg/kg intraperitoneally (i.p.), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy...
July 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27069541/dexmedetomidine-alleviates-postoperative-cognitive-dysfunction-by-inhibiting-neuron-excitation-in-aged-rats
#19
Bo Xiong, Qiqing Shi, Hao Fang
The perioperative stress response is one of the factors leading to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) can reduce the stress response and hippocampus neuroapoptosis, but its mechanism of action on POCD remains unknown. This study investigated the protective effect and possible mechanism of Dex on POCD in aged rats. Ninety-six aged male rats were randomly divided into four groups (n = 24 rats per group): a non-surgical control group, a surgical (model) group, a surgical group receiving a high dose of Dex (12 μg/kg), and a surgical group receiving a low dose of Dex (3 μg/kg)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27035665/astaxanthin-reduces-isoflurane-induced%C3%A2-neuroapoptosis-via-the-pi3k-akt-pathway
#20
Chun-Mei Wang, Xiao-Lan Cai, Qing-Ping Wen
Astaxanthin is an oxygen-containing derivative of carotenoids that effectively suppresses reactive oxygen and has nutritional and medicinal value. The mechanisms underlying the effects of astaxanthin on isoflurane‑induced neuroapoptosis remain to be fully understood. The present study was conducted to evaluate the protective effect of astaxanthin to reduce isoflurane‑induced neuroapoptosis and to investigate the underlying mechanisms. The results demonstrated that isoflurane induced brain damage, increased caspase‑3 activity and suppressed the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway in an in vivo model...
May 2016: Molecular Medicine Reports
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