Neuroprotective Effects of HU-211 on Brain Damage Resulting from Soman-Induced Seizures

• Published in: Annals of the New York Academy of Sciences Vol. 890; no. 1; pp. 505 - 514
• Main Authors: FILBERT, MARGARET G., FORSTER, JEFFRY S., SMITH, C. DAHLEM, BALLOUGH, GERALD P. H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.1999
• Subjects: Animals; Cholinesterase Inhibitors - adverse effects; Dronabinol - analogs & derivatives; Dronabinol - pharmacology; Male; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Seizures - chemically induced; Soman - adverse effects; Temporal Lobe - drug effects; Temporal Lobe - pathology; Time Factors
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.1999.tb08032.x

Neuroprotective effects of HU‐211 (dexanabinol), a synthetic nonpsychotropic analog of tetrahydrocannabinol, on brain damage resulting from soman‐induced seizures were examined in male Sprague‐Dawley rats challenged with 1.6 LD50 soman. At 5 or 40 min after onset of seizures, the rats were given an intraperitoneal injection of 25 mg/kg HU‐211. All rats that received soman showed electrocorticographic (ECoG) evidence of sustained seizures and status epilepticus for 4–6 hr. HU‐211 had no effect on either the strength or duration of seizure activity. Administration of HU‐211 at 5 min after seizure onset reduced median lesion volume 86% (as assessed by microtubule‐associated protein 2 (MAP2)‐negative staining), and when administered 40 min post‐onset, the reduction in necrosis was 81.5% despite the presence of continuous seizures for 4–5 hr. These observations were corroborated by hemotoxylin and eosin (H&E) histopathological assessment that showed a significant reduction in piriform cortical neuronal damage in HU‐211‐treated animals. It is concluded that HU‐211 provides considerable neuroprotection against brain damage produced by soman‐induced seizures.