Neuroprotection from soman-induced seizures in the rodent: evaluation with diffusion- and T2-weighted magnetic resonance imaging.
Exposure to the organophosphate nerve agent soman produces seizures that in turn lead to neuropathology. This study describes the temporal and spatial evolution of brain pathology following soman-induced convulsions and the attenuation of these alterations after neuroprotective intervention with magnetic resonance imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and thalamus exhibited significant decreases (23%) in apparent diffusion coefficients (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements declined significantly at 12 h (37%) returning to near normal values by 24 h. Histopathological analyses confirmed moderate cell loss within the hippocampus and piriform cortex. Together these findings suggest that initial cell death was resolved through regional cellular remodeling. Pharmacological countermeasures were administered in the form of diazepam, a benzodiazepine anticonvulsant, or gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied immediately after soman exposure prevented acute ADC changes. However the presence of edema, using T2 measurements, was detected at 3 h within the retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34% below normal). GK-11 therapy appeared to prevent most of these changes. However at 7 days after soman, a decrease (17%) in ADC was observed in the piriform cortex. Pathology was confined to the piriform cortex suggesting that this region is more difficult to protect. This is the first report that provides temporal and spatial resolution using MRI with histological correlation of pharmacological interventions against soman-mediated seizure-induced neuropathology.
Department of Medical Imaging, College of Medicine, Royal University Hospital, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Sask., Canada.
Yusuf A
YA
Bhagat
André
A
Obenaus
Murray G
MG
Hamilton
John
J
Mikler
Edward J
EJ
Kendall
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D016923:Cell Death; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D053138:Cyclohexenes; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use*; D038524:Diffusion Magnetic Resonance Imaging; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D012999:Soman; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000927:Anticonvulsants; D003510:Cyclohexanes; D053138:Cyclohexenes; D018696:Neuroprotective Agents; D010880:Piperidines; C070707:gacyclidine; D012999:Soman; D003975:Diazepam