Format

Send to

Choose Destination
Neurotoxicol Teratol. 2016 Jul-Aug;56:81-86. doi: 10.1016/j.ntt.2016.05.002. Epub 2016 May 17.

Pharmacological blockade of the calcium plateau provides neuroprotection following organophosphate paraoxon induced status epilepticus in rats.

Author information

1
Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
2
Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.
3
Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: Robert.DeLorenzo@vcuhealth.org.

Abstract

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10mg/kg, i.m.) and carisbamate (90mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival.

KEYWORDS:

Calcium; Carisbamate; Cell death; Dantrolene; Paraoxon; Status epilepticus

PMID:
27224207
PMCID:
PMC4935577
DOI:
10.1016/j.ntt.2016.05.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center