Abstract：
:The chemical warfare nerve agent, soman irreversibly inhibits acetylcholinesterase (AChE) leading to hypercholinergy and seizures which trigger glutamate toxicity and status epilepticus ultimately resulting in neuropathology and neurobehavioral deficits. The standard emergency treatment comprising of anticholinergic, AChE reactivator and anticonvulsant does not completely protect against soman toxicity. We have evaluated imidazenil, a new anticonvulsant imidazo benzodiazepine with high affinity and intrinsic efficacy at α5-, α2-, and α3- but low intrinsic efficacy at α1-containing GABA(A) receptors and is devoid of cardiorespiratory depression, sedative/hypnoitc and amnestic actions and does not elicit tolerance and dependence liabilities unlike diazepam, for protection against soman toxicity. Guinea pigs implanted with bipotential radiotelemetry probes for recording EEG and ECG were administered with 26 μg/kg pyridostigmine bromide 30 min prior to 2× LD(50) soman exposure and 1 min later treated with a combination of 2mg/kg atropine sulfate and 25mg/kg 2-pralidoxime and various doses of imidazenil. Intramuscular administration of imidazenil, dose-dependently protected against 2× LD(50) of soman toxicity up to 1mg/kg. Further increase in the dose of imidazenil to 2.5mg/kg was less effective than 1mg/kg probably due to non-specific actions at sites other than GABA(A) receptors. Compared to vehicle group, 1mg/kg imidazenil treatment showed optimal increase in survival rate, reduction in behavioral manifestations and high power of EEG spectrum as well as neuronal necrosis. These data suggest that imidazenil is an effective anticonvulsant for medical countermeasure against soman-induced toxicity.
journal_name
Neurotoxicologyjournal_title
Neurotoxicologyauthors
Wang Y,Oguntayo S,Wei Y,Wood E,Brown A,Jensen N,Auta J,Guiodotti A,Doctor BP,Nambiar MPdoi
10.1016/j.neuro.2011.12.018subject
Has Abstractpub_date
2012-03-01 00:00:00pages
169-77issue
2eissn
0161-813Xissn
1872-9711pii
S0161-813X(12)00002-2journal_volume
33pub_type
杂志文章相关文献
NEUROTOXICOLOGY文献大全abstract：:Neurofilament (NF) protein crosslinking has been proposed as the ultimate pathogenetic mechanism underlying the neuropathies caused by the gamma-diketones 2,5-hexanedione (HD) and 3,4-dimethyl-2,5-hexanedione (DMHD). Mammalian models have been used to investigate this hypothesis, but alternative experimental models ar...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Exposure to anesthetic gases is known to alter certain structures and functions of the central nervous system. As the effects of long-term exposure on balance control mechanisms have been the subject of few investigations, these were evaluated in 53 operating room personnel exposed to anesthetic gases and in 53 non-ex...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2004.11.002
更新日期：2005-03-01 00:00:00
abstract：:The time dependent tissue/organ distribution of Pb resulting from repeated intragastric exposure of the preweanling rat to Pb acetate was investigated. On the day of parturition, 12 dams were assigned randomly either to control (nonhandled) or Pb-treated groups and their litters were culled to 8 pups. On days 6, 9, 12...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:Rats were anesthetized with urethane, implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, and exposed to different doses of lindane. Analysis of evoked field potential responses indicated that lindane exposure resulted in consistent, dose-dependent changes. Two separable effect...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Although it is well known that lead (Pb2+0 acutely blocks voltage-gated calcium currents (VGCCs) in mammalian neurons, little is known about the long-term effects of continuous exposure to this metal on VGCCs. In the present study, the effects of chronic lead exposure on VGCCs (with barium ions as the charge carrier) ...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:Methylmercury has been designated a "behavioral teratogen" because of its ability to evoke abnormalities in the absence of gross morphological damage to the developing brain. Recent work indicates that exposure to doses of methylmercury associated with neurobehavioral actions causes early alterations in brain ornithin...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：
更新日期：1987-04-01 00:00:00
abstract：BACKGROUND:The organophosphate insecticide chlorpyrifos (CPF), widely used for agricultural purposes, has been linked to neurodevelopmental deficits. Possible motor effects at low to moderate levels of exposure have not been evaluated. METHODS:Prenatal exposure to CPF was measured in umbilical cord blood in a sample o...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2015.09.004
更新日期：2015-12-01 00:00:00
abstract：:Low-to-moderate level developmental and adult lead exposure produces retinal dysfunction and/or degeneration in humans and experimental animals. Although high level in vivo or in vitro lead disrupts blood-brain-barrier tight junctions and increases its permeability, the blood-retinal-barrier (BRB) has not been examine...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2016.09.013
更新日期：2016-12-01 00:00:00
abstract：:Olfactory transport of represents an important mechanism for direct delivery of certain metals to the central nervous system (CNS). The objective of this study was to determine whether inhaled tungsten (W) undergoes olfactory uptake and transport to the rat brain. Male, 16-week-old, Sprague-Dawley rats underwent a sin...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2009.02.004
更新日期：2009-05-01 00:00:00
abstract：:3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cult...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2018.06.002
更新日期：2018-07-01 00:00:00
abstract：:Glial cells and their interactions with neurons play vital roles during the ontogeny of the nervous system and in the adult brain. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in uter...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：10.1016/s0161-813x(01)00037-7
更新日期：2001-10-01 00:00:00
abstract：BACKGROUND:Prenatal exposure to p,p'-DDE is associated with impairments in motor development during the first year of life, with no related repercussions on mental or motor development at 12-30 months and with impairments in cognitive areas, but not in perceptual and motor areas at preschool age. However, its associati...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2014.12.011
更新日期：2015-03-01 00:00:00
abstract：:Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are becoming widespread environmental pollutants, as indicated by studies on sentinel animal species, as well as humans. Of particular concern are the reported increasingly high levels of PBDEs in human milk, as should be given that almos...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：10.1016/S0161-813X(03)00020-2
更新日期：2003-06-01 00:00:00
abstract：:Gulf War Illness (GWI) manifests a multitude of symptoms, including neurological and immunological, and approximately a third of the 1990-1991 Gulf War (GW) veterans suffer from it. This study sought to characterize the acute neurochemical (monoamine) and neuroinflammatory profiles of two established GWI animal models...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2019.12.012
更新日期：2020-03-01 00:00:00
abstract：:N-Butylbenzenesulfonamide (NBBS) is widely used as a plasticizer in polyacetals, polyamides, and polycarbonates and has been found in ground water and effluent from wastewater treatment sites. The compound is lipophilic and distributes rapidly to the brain but also clears rapidly and shows little evidence of accumulat...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2012.07.002
更新日期：2012-12-01 00:00:00
abstract：:In the past six years, our research group has investigated the relationship between lead exposure and mental and behavioural development. This has been carried out through studies in children and animals. Earlier studies in children have shown that associations might be expected between environmental exposure to lead ...
journal_title：Neurotoxicology
pub_type： 杂志文章,评审
doi：
更新日期：1986-07-01 00:00:00
abstract：:The effects of lead (0.0, 0.1, or 1 microM) on subcellular sites in primary astroglial cultures were quantitated with the use of vital fluorescent probes (fluorescence bioassays). Evaluation of cellular glutathione levels with monochlorobimane revealed a reduction in glutathione content after only 7 hr of Pb treatment...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：OBJECTIVE:To investigate the nature of parkinsonism associated with liver cirrhosis, which entails examination of the integrity of the nigrostriatal dopaminergic system. METHODS:Consecutive patients who had concurrent liver cirrhosis and parkinsonism were investigated with MRI and dopamine transporter (DAT) single-pho...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2010.05.002
更新日期：2010-08-01 00:00:00
abstract：:Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed ...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2013.02.008
更新日期：2013-05-01 00:00:00
abstract：:Sevoflurane, a commonly used inhaled anesthetic, can induce neuronal apoptosis in the developing rodent brain and correlate with functional neurological impairment later in life. However, the mechanisms underlying these deleterious effects of sevoflurane remain unclear and no effective treatment is currently available...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2014.11.003
更新日期：2015-01-01 00:00:00
abstract：:Prediction of neurotoxic effects is a key feature in the toxicological profile of many compounds and therefore is required by regulatory testing schemes. Nowadays neurotoxicity assessment required by the OECD and EC test guidelines is based solely on in vivo testing, evaluating mainly effects on neurobehavior and neur...
journal_title：Neurotoxicology
pub_type：
doi：10.1016/j.neuro.2008.02.008
更新日期：2008-05-01 00:00:00
abstract：:1-Bromopropane (1-BP) has been widely used as a substitute for chlorofluorocarbon that destroys the ozone layer. Although the central neurotoxicity of 1-BP has been recently reported, a molecular mechanism is not clear. In particular, the effects on cells in brain have not been fully analyzed. Here, we studied the eff...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2006.05.015
更新日期：2007-03-01 00:00:00
abstract：:The authors carried out neurological examination, visual evoked potentials (VEP) examination, and electromyography (EMG) on 77 workers, aged 21-61 yrs, who were exposed occupationally to Hgo vapors for 1-20 yrs (mean 9 yrs). The mean air-borne concentration of Hgo was 0.25 mg/m3 (range 0.02-1.00 mg m3), and the mean H...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：BACKGROUND:Long-term exposure to organic solvents may lead to chronic solvent induced encephalopathy (CSE) in painters. In combination with reduction of exposure, a workers' health surveillance programme was developed, resulting in a three-stage CSE screening procedure for early neurobehavioural changes possibly predic...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2012.05.015
更新日期：2012-08-01 00:00:00
abstract：:Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempter...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2020.11.002
更新日期：2021-01-01 00:00:00
abstract：:Given the well-known antioxidant and neuroprotective properties of quercetin, the aim of this work was to evaluate the effects of quercetin stabilized by microencapsulation at two doses (10 mg kg-1 and 100 mg kg-1) on the oxidative/antioxidant status, number and morphological features of ICC, nitrergic neurons and M2-...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2020.01.011
更新日期：2020-03-01 00:00:00
abstract：:The N-oxide of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the major metabolite found in vivo and excreted in urine after the parenteral administration of the neurotoxicant, MPTP. In mice (C57BL/6), stereotaxic injection of MPTP N-oxide (15 micrograms) into the neostriatum produced dopamine (DA) depletion s...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:Kainic acid (KA) was injected intraperitoneally into rats at a dose (9 mg/kg) which produced status epilepticus in approximately 50% of the animals. Rats were categorized into groups that displayed status epilepticus, partial seizures or no effect in the 4 hr following kainic acid injection. Behavioral and morphologic...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Manganese (Mn) may produce neurotoxicity in man through inhalation of Mn dust. Animals exposed to excessive Mn develop neurological abnormalities, and neuropathological lesions in the brain mainly in the globus pallidus with decreased concentrations of the neurotransmitter, dopamine (DA), in the brain. Monkeys exposed...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:For the diagnosis of patients suspected of chronic solvent-induced encephalopathy (CSE), it would be helpful if the applied cognitive tests show a characteristic profile of impairment in this disease. We investigated the existence of such a profile. In 1997-2006 two expert teams in The Netherlands systematically exami...
journal_title：Neurotoxicology
pub_type： 杂志文章
doi：10.1016/j.neuro.2012.06.005
更新日期：2012-08-01 00:00:00
