PROPOFOL INHIBITION OF LITHIUM-PILOCARPINE-INDUCED STATUS EPILEPTICUS
Abstract number :
1.046
Submission category :
Year :
2002
Submission ID :
1455
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Steven L. Peterson, Rebecca S. Purvis, James W. Griffith. College of Pharmacy, University of New Mexico, Albuquerque, NM; Comparative Medicine, Penn St. Milton S. Hershey Medical Center, Hershey, PA
RATIONALE: The status epilepticus (SE) induced by lithium-pilocarpine (Li-pilo) treatment in rats produces neuropathology similar to that of the organophosphrous (OP) nerve agents. Since ongoing cholinergic convulsions are difficult to arrest with current treatments, this study was designed to determine the efficacy of the nonbarbiturate anesthetic propofol against Li-pilo-induced SE.
METHODS: Anesthetized Sprague Dawley rats were implanted with ECoG electrodes. After 7-10 days of recovery, they were administered 3 mmol/kg LiCl s.c. followed 20-24 hours later by 25 mg/kg pilocarpine s.c. Propofol was administered i.p. either immediately following pilocarpine exposure, after 5 minutes of SE or after 3 hours of SE as defined by continuous, high amplitude ECoG activity. Animals were sacrificed 24 hours following pilocarpine and the brains sectioned for hematoxylin and eosin (H&E) stain.
RESULTS: All animals survived the 24-hour period following 3 hours of SE when treated with 55 mg/kg propofol, only half (3/6) survived following 50 mg/kg propofol. All subsequent experiments tested 55 mg/kg propofol. Propofol prevented SE onset after pilocarpine exposure and terminated all seizure activity when administered during SE. The latency to inhibit SE was longer following 3 hour SE than 5 minute SE (20.8 min vs. 12.8 min, t-test, P[lt]0.05). Rats experiencing 3 hour SE had substantial neuropathology in the perirhinal and especially the piriform cortex with all animals demonstrating greater than 40 % necrotic or malacic tissue in that area. Significantly less neuropathology was found in the perirhinal and piriform cortex of rats treated with propofol following 5 minutes of SE as determined by histopathology rating (Mann-Whitney U test, P[lt]0.025) and optical density measurements (t-test, P[lt]0.01) of H&E stained sections.
CONCLUSIONS: This study is the first to demonstrate that propofol effectively terminates ongoing Li-pilo-induced SE and decreases neuropathology associated with those seizures. Propofol may serve as effective treatment of OP nerve exposure.
[Supported by: This work was supported by Department of Army award no. DAMD 17-01-1-0794. The US Army Medical Research Acquisition Activiy, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding and administering acquisition office.]