Abstract | INTRODUCTION: Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post- poisoning cognitive dysfunction. METHODS: Sprague-Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 - no central antidotal treatment (n=10); group 2 - treated with midazolam (MID) at 30 min after poisoning (n=9), group 3 - treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel (1)H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. RESULTS: All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID+SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24h after poisoning. MID and MID+SCOP prevented much of the 3h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings ( brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4-0.75 (p<0.05). CONCLUSIONS:
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Authors | Shai Shrot, Maya Tauber, Arthur Shiyovich, Nadav Milk, Yossi Rosman, Arik Eisenkraft, Tamar Kadar, Michael Kassirer, Yoram Cohen |
Journal | Neurotoxicology
(Neurotoxicology)
Vol. 48
Pg. 206-16
(May 2015)
ISSN: 1872-9711 [Electronic] Netherlands |
PMID | 25912464
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Cholinesterase Reactivators
- Neuroprotective Agents
- Aspartic Acid
- Obidoxime Chloride
- Atropine
- N-acetylaspartate
- Scopolamine
- Creatine
- Choline
- Paraoxon
- Midazolam
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Topics |
- Animals
- Aspartic Acid
(analogs & derivatives, metabolism)
- Atropine
(pharmacology)
- Behavior, Animal
- Brain
(drug effects, metabolism, pathology)
- Brain Edema
(chemically induced, drug therapy, metabolism, pathology, physiopathology, psychology)
- Choline
(metabolism)
- Cholinesterase Reactivators
(pharmacology)
- Cognition
- Creatine
(metabolism)
- Disease Models, Animal
- Drug Therapy, Combination
- Early Diagnosis
- Magnetic Resonance Imaging
- Male
- Maze Learning
- Midazolam
(pharmacology)
- Neuroprotective Agents
(pharmacology)
- Obidoxime Chloride
(pharmacology)
- Organophosphate Poisoning
(drug therapy, metabolism, pathology, physiopathology, psychology)
- Paraoxon
- Predictive Value of Tests
- Proton Magnetic Resonance Spectroscopy
- Rats, Sprague-Dawley
- Scopolamine
(pharmacology)
- Time Factors
- Weight Loss
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