Beneficial Outcome of Urethane Treatment Following Status Epilepticus in a Rat Organophosphorus Toxicity Model

ENeuro
Asheebo RojasRaymond Dingledine

Abstract

The efficacy of benzodiazepines to terminate electrographic status epilepticus (SE) declines the longer a patient is in SE. Therefore, alternative methods for ensuring complete block of SE and refractory SE are necessary. We compared the ability of diazepam and a subanesthetic dose of urethane to terminate prolonged SE and mitigate subsequent pathologies. Adult Sprague Dawley rats were injected with diisopropylfluorophosphate (DFP) to induce SE. Rats were administered diazepam (10 mg/kg, ip) or urethane (0.8 g/kg, s.c.) 1 h after DFP-induced SE and compared to rats that experienced uninterrupted SE. Large-amplitude and high-frequency spikes induced by DFP administration were quenched for at least 46 h in rats administered urethane 1 h after SE onset as demonstrated by cortical electroencephalography (EEG). By contrast, diazepam interrupted SE but seizures with high power in the 20- to 70-Hz band returned 6-10 h later. Urethane was more effective than diazepam at reducing hippocampal neurodegeneration, brain inflammation, gliosis and weight loss as measured on day 4 after SE. Furthermore, rats administered urethane displayed a 73% reduction in the incidence of spontaneous recurrent seizures after four to eight weeks and a 90% re...Continue Reading

Citations

May 16, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Brad A HobsonPamela J Lein
Feb 11, 2020·Annals of the New York Academy of Sciences·Marson PutraThimmasettappa Thippeswamy
Sep 23, 2020·Annals of the New York Academy of Sciences·Laxmikant S DeshpandeRobert J DeLorenzo
Jan 8, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Asheebo RojasThota Ganesh
Aug 31, 2019·ACS Chemical Neuroscience·Asheebo RojasRaymond Dingledine

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Methods Mentioned

BETA
protein assay
ELISA
PCR
pharmacotherapy
sedation

Software Mentioned

AxioVision AC
Python
OriginLab
NicoletOne reader
R
GraphPad Prism
Origin
GraphPad
NicoletOne recorder
Spike2

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