Early brain magnetic resonance imaging can predict short and long-term outcomes after organophosphate poisoning in a rat model

•Paraoxon was used to induce status epilepticus and brain damage in a rat model.•MRI showed in vivo alterations in brain structure and function after acute poisoning.•Weight loss and MWM were used to assess post-poisoning clinical deterioration.•We found a correlation between early imaging parameters and clinical outcomes.•Delayed treatment provides only transient neuroprotection against the neuronal damage. 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. 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 30min after poisoning (n=9), group 3 – treated with a combination of MID and scopolamine (SCOP) at 30min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel 1H 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. All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3h 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