Neuroprotective effects of HU-211 on brain damage resulting from soman-induced seizures.
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.
Filbert
M G
MG
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USA. Margaret.Filbert@AMEDD.Army.Mil
Forster
J S
JS
Smith
C D
CD
Ballough
G P
GP
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000009:adverse effects; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced; D012999:Soman / Q000009:adverse effects; D013702:Temporal Lobe / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D013759:Dronabinol; D012999:Soman; C062018:HU 211