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Neurotoxicology. 2018 May;66:170-178. doi: 10.1016/j.neuro.2017.11.009. Epub 2017 Nov 26.

A magnetic resonance imaging study of early brain injury in a rat model of acute DFP intoxication.

Author information

1
Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA, 95616, United States. Electronic address: bahobson@ucdavis.edu.
2
Center for Molecular and Genomic Imaging, University of California, Davis, College of Engineering, Davis, CA, 95616, United States. Electronic address: djrowland@ucdavis.edu.
3
Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA, 95616, United States. Electronic address: ssupasai@ucdavis.edu.
4
Department of Public Health Sciences, University of California, Davis, School of Medicine, Davis, CA, 95616, United States. Electronic address: djharvey@ucdavis.edu.
5
Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA, 95616, United States. Electronic address: pjlein@ucdavis.edu.
6
Biomedical Magnetic Resonance Laboratory, Mallinckrodt Institute of Radiology, School of Medicine,Washington University in St. Louis, St. Louis, MO, 63110, United States. Electronic address: garbow@wustl.edu.

Abstract

Current treatments for seizures induced by organophosphates do not protect sufficiently against progressive neurodegeneration or delayed cognitive impairment. Developing more effective therapeutic approaches has been challenging because the pathogenesis of these delayed consequences is poorly defined. Using magnetic resonance imaging (MRI), we previously reported brain lesions that persist for months in a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP). However, the early spatiotemporal progression of these lesions remains unknown. To address this data gap, we used in vivo MRI to longitudinally monitor brain lesions during the first 3 d following acute DFP intoxication. Adult male Sprague Dawley rats acutely intoxicated with DFP (4mg/kg, sc) were MR imaged at 6, 12, 18, 24, 48, 72h post-DFP, and their brains then taken for correlative histology to assess neurodegeneration using FluoroJade C (FJC) staining. Acute DFP intoxication elicited moderate-to-severe seizure activity. T2-weighted (T2w) anatomic imaging revealed prominent lesions within the thalamus, piriform cortex, cerebral cortex, hippocampus, corpus striatum, and substantia nigra that corresponded to neurodegeneration, evident as bands of FJC positive cells. Semi-quantitative assessment of lesion severity demonstrated significant regional variation in the onset and progression of injury, and suggested that lesion severity may be modulated by isoflurane anesthesia. These results imply that the timing of therapeutic intervention for attenuating brain injury following OP intoxication may be regionally dependent, and that longitudinal assessment of OP-induced damage by MRI may be a powerful tool for assessing therapeutic response.

KEYWORDS:

In vivo imaging; Neuropathology; Organophosphate; Seizure; T2-weighted MRI

PMID:
29183789
PMCID:
PMC5940565
DOI:
10.1016/j.neuro.2017.11.009
[Indexed for MEDLINE]
Free PMC Article

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