Using MRI for the assessment of paraoxon-induced brain damage and efficacy of antidotal treatment

• Published in: Journal of applied toxicology 2012-06, Vol.32 (6), p.409-416
• Main Authors: Rosman, Yossi, Eisenkraft, Arik, Krivoy, Amir, Schein, Ophir, Makarovski, Igor, Shrot, Shai, Ramaty, Erez, Shilderman, Eugenia Bloch, Kapon, Joseph, Gilat, Eran, Kadar, Tamar, Maier, Stephan, Daniels, Dianne, Shneor, Ran, Salomon, Sharona, Tamar, Gregori, Last, David, Mardor, Yael
• Format: Article
• Language: English
• Subjects: Animals; Antidotes - pharmacology; Assessments; Atropine - pharmacology; Biological and medical sciences; Brain; Brain - drug effects; Brain - pathology; Brain damage; Brain Diseases - chemically induced; Brain Diseases - diagnosis; Brain Diseases - metabolism; Cholinergic Antagonists - pharmacology; Cholinesterase Inhibitors - toxicity; Cholinesterase Reactivators - pharmacology; DWMRI; Effectiveness; GABA Modulators - pharmacology; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical sciences; midazolam; Midazolam - pharmacology; MRI; Obidoxime Chloride - pharmacology; organophosphate; Organophosphates; paraoxon; Paraoxon - toxicity; Pesticides, fertilizers and other agrochemicals toxicology; Poisoning; Rats; Rats, Sprague-Dawley; scopolamine; Scopolamine Hydrobromide - pharmacology; Toxicology
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1715

ABSTRACT Organophosphate intoxication induces neural toxicity as demonstrated in histological analysis of poisoned animals. Diffusion‐weighted magnetic resonance imaging (DWMRI) enables early noninvasive characterization of biological tissues based on their water diffusion characteristics. Our objectives were to study the application of MRI for assessment of paraoxon‐induced brain damage and the efficacy of antidotal treatments. Seventy‐six rats were poisoned with paraoxon followed by treatment with atropine and obidoxime. The rats were then divided into five treatment groups consisting of midazolam after 1 or 30 min, scopolamine after 1 or 30 min and a no anticonvulsant treatment group. Five untreated rats served as controls. Animals underwent MRI on days 1, 8, 15, 29 and 50 post poisoning. Histological evaluation was performed on representative rat brains. Acute DWMRI effects, such as enhancement of temporal brain regions, and chronic effects such as ventricular enlargement and brain atrophy, depicted on T2‐weighted MRI, were significantly more prominent in late anticonvulsant treatment groups. There was no significant difference between the neuroprotective effects of midazolam and scopolamine as shown by DWMRI. Early MRI abnormalities were found to correlate significantly with histological analysis of samples obtained 15 days post treatment. In conclusion, our results demonstrate the feasibility of using DWMRI for depiction of early cytotoxic response to paraoxon and T2‐weighted MRI for later changes, thus enabling assessment of early/late brain damage as well as treatment efficacy in rats. The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning. Copyright © 2011 John Wiley & Sons, Ltd. This work demonstrates the feasibility of using DWMRI for depiction of early cytotoxic response to Paraoxon and T2‐weighted MRI for later changes, thus enabling assessment of early/late brain damage as well as treatment efficacy in rats. The ability to depict these changes early and noninvasively may be applied clinically in the acute phase of organophosphate poisoning.