Magnetic resonance imaging reveals progressive brain injury in rats acutely intoxicated with diisopropylfluorophosphate

Brad A. Hobson, Sílvia Sisó, Douglas J. Rowland, Danielle J Harvey, Donald A. Bruun, Joel R. Garbow, Pamela J Lein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for 1 month after acute intoxication with diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im) exhibited moderate-to-severe seizure behavior. T2-weighted and diffusion-weighted MR imaging prior to DFP exposure and at 3, 7, 14, 21, or 28 days postexposure revealed prominent lesions, tissue atrophy, and ventricular enlargement in discrete brain regions. Lesions varied in intensity and/or extent over time, with the overall magnitude of injury strongly influenced by seizure severity. Importantly, lesions detected by MRI correlated spatially and temporally with histological evidence of brain pathology. Analysis of histogram parameters extracted from frequency distributions of regional apparent diffusion coefficient (ADC) values identified the standard deviation and 90th percentile of the ADC as robust metrics for quantifying persistent and progressive neuropathological changes. The interanimal and interregional variations observed in lesion severity and progression, coupled with potential reinjury following spontaneous recurrent seizures, underscore the advantages of using in vivo imaging to longitudinally monitor neuropathology and, ultimately, therapeutic response, following acute OP intoxication.

Original languageEnglish (US)
Pages (from-to)342-353
Number of pages12
JournalToxicological Sciences
Volume157
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Isoflurophate
Magnetic resonance imaging
Brain Injuries
Organophosphates
Rats
Brain
Seizures
Magnetic Resonance Imaging
Imaging techniques
Magnetic resonance
Pyridostigmine Bromide
Pathology
Atropine
Status Epilepticus
Wounds and Injuries
Mood Disorders
Atrophy
Sprague Dawley Rats
Tissue
Neuropathology

Keywords

  • Diffusion-weighted MRI
  • In vivo imaging
  • Organophosphate
  • T2-weighted MRI

ASJC Scopus subject areas

  • Toxicology

Cite this

Magnetic resonance imaging reveals progressive brain injury in rats acutely intoxicated with diisopropylfluorophosphate. / Hobson, Brad A.; Sisó, Sílvia; Rowland, Douglas J.; Harvey, Danielle J; Bruun, Donald A.; Garbow, Joel R.; Lein, Pamela J.

In: Toxicological Sciences, Vol. 157, No. 2, 2017, p. 342-353.

Research output: Contribution to journalArticle

Hobson, Brad A. ; Sisó, Sílvia ; Rowland, Douglas J. ; Harvey, Danielle J ; Bruun, Donald A. ; Garbow, Joel R. ; Lein, Pamela J. / Magnetic resonance imaging reveals progressive brain injury in rats acutely intoxicated with diisopropylfluorophosphate. In: Toxicological Sciences. 2017 ; Vol. 157, No. 2. pp. 342-353.
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