title: Using MRI for the assessment of paraoxon-induced brain damage and efficacy of antidotal treatment.
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.
authors.affiliation: CBRN Medicine Branch, Medical Corps HQ, IDF, Israel. rosmanyossi@gmail.com
authors.forename: Yossi
authors.initials: Y
authors.lastname: Rosman
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
authors.forename: Amir
authors.initials: A
authors.lastname: Krivoy
authors.forename: Ophir
authors.initials: O
authors.lastname: Schein
authors.forename: Igor
authors.initials: I
authors.lastname: Makarovski
authors.forename: Shai
authors.initials: S
authors.lastname: Shrot
authors.forename: Erez
authors.initials: E
authors.lastname: Ramaty
authors.forename: Eugenia Bloch
authors.initials: EB
authors.lastname: Shilderman
authors.forename: Joseph
authors.initials: J
authors.lastname: Kapon
authors.forename: Eran
authors.initials: E
authors.lastname: Gilat
authors.forename: Tamar
authors.initials: T
authors.lastname: Kadar
authors.forename: Stephan
authors.initials: S
authors.lastname: Maier
authors.forename: Dianne
authors.initials: D
authors.lastname: Daniels
authors.forename: Ran
authors.initials: R
authors.lastname: Shneor
authors.forename: Sharona
authors.initials: S
authors.lastname: Salomon
authors.forename: Gregori
authors.initials: G
authors.lastname: Tamar
authors.forename: David
authors.initials: D
authors.lastname: Last
authors.forename: Yael
authors.initials: Y
authors.lastname: Mardor
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009768:Obidoxime Chloride / Q000494:pharmacology; D010261:Paraoxon / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D000931:Antidotes; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018757:GABA Modulators; D009768:Obidoxime Chloride; D001285:Atropine; D012601:Scopolamine; D010261:Paraoxon; D008874:Midazolam