Publications by authors named "Grauer E"

Background: Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.

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The COVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models included the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of human COVID-19. A group activity of animals in their home cage continuously monitored by the HCMS100 (Home cage Monitoring System 100) was used as a sensitive marker of disease, successfully detecting morbidity symptoms of SARS-CoV-2 infection in hamsters and in K18-hACE2 mice.

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The development of refractory status epilepticus (SE) induced by sarin intoxication presents a therapeutic challenge. In our current research we evaluate the efficacy of a delayed combined triple treatment in ending the abnormal epileptiform seizure activity (ESA) and the ensuing of long-term neuronal insult. SE was induced in male Sprague-Dawley rats by exposure to 1.

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Large numbers of rodents are often used in the study of disease progression and in the evaluation of its potential treatments. To avoid subjective observation and to minimize home cage interference, we developed a computerized home cage monitoring system (HCMS100) based on a standard cage rack adapted with a single laser beam and a detector mounted on each cage, enabling to monitor mice movements based on laser beam interruptions. This retrofit system provided continuous and uninterrupted monitoring of spontaneous movement of a group of mice in a home cage.

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Background: Sarin is an irreversible organophosphate cholinesterase inhibitor. Following toxic signs, an extensive long-term brain damage is often reported. Thus, we evaluated the efficacy of a novel anticonvulsant drug retigabine, a modulator of neuronal voltage gated K channels, as a neuroprotective agent following sarin exposure.

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The La-related protein 7 (LARP7) forms a complex with the nuclear 7SK RNA to regulate RNA polymerase II transcription. It has been implicated in cancer and the Alazami syndrome, a severe developmental disorder. Here, we report a so far unknown role of this protein in RNA modification.

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Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic, volatile warfare agent. Rats and guinea pigs exposed to sarin display cholinergic excitotoxicity which includes hyper-salivation, respiratory distress, tremors, seizures, and death. Here we focused on the characterization of the airways injury induced by direct exposure of the lungs to sarin vapor and compared it to that induced by the intramuscularly route.

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A common consequence of exposure to organophosphate nerve agents is the centrally mediated seizure activity that appears even after conventional treatment with atropine and oximes. We have previously demonstrated a major inflammatory response with subsequent brain damage which was correlated with the duration of the sarin-induced seizures (Chapman et al., 2006).

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Objective: Posttraumatic stress disorder (PTSD) is frequently associated with depression and anxiety, but the nature of the relationship is unclear. By removing mood and anxiety diagnostic criteria, the 11th edition of the International Classification of Diseases (ICD-11) aims to delineate a distinct PTSD phenotype. We examined the effect of implementing ICD-11 criteria on rates of codiagnosed depression and anxiety in survivors with recent PTSD.

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This work focused on sex differences in rats exposed to sarin. Females were found to be more sensitive to sarin toxicity (LD50 67 μg/kg) than males (88 μg/kg), showed less acute hypothermic effects than males (at 120 min post sarin, 3.1 ± 1.

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Eye exposure to organophosphate (OP) irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. The aim of this study was to find an anticholinergic antidote, which would counteract miosis and visual impairment induced by the nerve agents sarin and VX with minimal untoward side-effects. Rat pupil width and light reflex were evaluated from 15 min up to 2 weeks following topical OP exposure with or without topical ocular treatment of atropine or homatropine or with a combined intramuscular treatment of trimedoxime (TMB-4) and atropine (TA).

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Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g.

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The antidotal treatment of organophosphates (OP) nerve agents (NA) poisoning is based on anticholinergics (e.g. atropine) combined with oxime reactivators (e.

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Rivastigmine, a reversible cholinesterase inhibitor, approved as a remedy in Alzheimer's disease, was suggested as pretreatment against nerve agents poisoning. We evaluated the pharmacokinetic, pharmacodynamic, physiologic, cognitive and emotional effects of repeated rivastigmine in young healthy male adults, in a double blind, placebo controlled crossover trial. Three groups completed 3 treatment periods: 0, 1.

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Sarin poisoned rats display a hyper-cholinergic activity including hypersalivation, tremors, seizures and death. Here we studied the time and dose effects of midazolam treatment following nerve agent exposure. Rats were exposed to sarin (1.

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Eye exposure to the extremely toxic organophosphorus sarin results in long-term miosis and visual impairment. As current treatment using atropine or homatropine eye drops may lead to considerable visual side effects, alternative combined treatments of intramuscular (im) oximes (16.8 µmol/kg, im) with atropine (0.

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Objective: Exposure to organophosphates (OP) may lead to a life threatening cholinergic crisis with death attributed to a rapidly progressive respiratory failure. In a toxicological mass casualty event involving organophosphate exposure, many of the victims may depend on immediate short-term ventilation to overcome the respiratory distress which may exhaust life supporting resources. In addition, the mandatory use of personal protective gear by first responders emphasizes the need for a noninvasive, easy-to-operate ventilation device.

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Sarin, a potent organophosphate cholinesterase inhibitor, induces an array of toxic effects including convulsions. Many antidotal treatments contain anticonvulsants to block seizure activity and the ensuing brain damage. Magnesium sulfate (MGS) is used to suppress eclamptic seizures in pregnant women with hypertension and was shown to block kainate-induced convulsions.

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Highly emotional, stress reactive BALB/c mice secrete more corticosterone in response to fear conditioning than the low stress reactive C57BL/6J mice. Fear memory to cue and context differs between the strains. We injected corticosterone at physiological concentrations (250 μg/kg i.

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The main injuries among victims of the terrorist act in the Tokyo subway resulted from sub-lethal inhalation and whole body exposure to sarin vapor. In order to study the long term effects of such exposure and to simulate these conditions, freely moving rats were exposed to sarin vapor (27.2±1.

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Alterations of nitric oxide (NO) metabolism in the brain have been associated with modifications of stress-related behavior in animal models. It has been generally assumed that these behavioral changes are due to the neuronal nitrosative activity. On the other hand, glial NO production has been demonstrated mainly as a slow reaction to brain insults through the activity of an inducible nitric oxide synthase (NOS) isoform (NOS2).

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The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult.

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Severe poisoning by inhibitors of cholinesterase (ChE) enzymes is often associated with prolonged central or peripheral neuronal damage. Oxotremorine is a cholinergic agonist known to induce acute hypothermia. Central and peripheral cholinergic signaling is involved in the induction of hypothermia as well as in its recovery.

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Background: It has been well accepted that glial cells in the central nervous system (CNS) produce nitric oxide (NO) through the induction of a nitric oxide synthase isoform (NOS2) only in response to various insults. Recently we described rapid astroglial, NOS2-dependent, NO production in the neocortex of healthy mice on a time scale relevant to neuronal activity. To explore a possible role for astroglial NOS2 in normal brain function we investigated a NOS2 knockout mouse (B6;129P2-Nos2(tm1Lau)/J, Jackson Laboratory).

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