Magnetic resonance imaging reveals that galantamine prevents structural brain damage induced by an acute exposure of guinea pigs to soman.
Galantamine, a drug used to treat Alzheimer's disease, has recently emerged as a potential medical countermeasure against the toxicity of organophosphorus (OP) compounds, including the nerve agent soman. Here, magnetic resonance imaging (MRI) was used to characterize the neurotoxic effects of soman and the ability of galantamine to prevent these effects in guinea pigs, the best non-primate model to predict the effectiveness of antidotes against OP toxicity in humans. The brains of treated and untreated guinea pigs were imaged using a clinical 3.0 Tesla MRI scanner at 48 h before and 6-7 h, 48 h and 7 days after their challenge with 1.0xLD50 soman (26.6 microg/kg, sc). Significant brain atrophy was observed among all untreated animals at 7 days after their challenge with soman. In mildly intoxicated animals, significant shortening of spin-spin relaxation times (T2) was observed in the thalamus and amygdala at 7h after the challenge. In severely intoxicated animals, T2 values and T2-weighted signal intensities increased significantly in the piriform cortex, hippocampus, thalamus and amygdala; in most regions, changes were long-lasting. Voxel-based morphometric analysis of the images revealed that other brain regions were also damaged in these animals. Neuronal loss was confirmed histopathologically. In animals that were treated with galantamine (8 mg/kg, im) 30 min prior to the exposure to soman, T2, T2-weighted signal intensities, and CSF volumes were largely unaffected. It is, therefore, concluded that galantamine can effectively prevent the structural brain damage induced by an acute exposure to soman.
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Rao P
RP
Gullapalli
Yasco
Y
Aracava
Jiachen
J
Zhuo
Edward
E
Helal Neto
Jiazheng
J
Wang
George
G
Makris
Istvan
I
Merchenthaler
Edna F R
EF
Pereira
Edson X
EX
Albuquerque
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001931:Brain Mapping; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005702:Galantamine / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D008279:Magnetic Resonance Imaging / Q000379:methods; D051579:Neurogranin / Q000235:genetics / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D018697:Nootropic Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012999:Soman / Q000633:toxicity*; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D012333:RNA, Messenger; D005702:Galantamine; D051579:Neurogranin; D012999:Soman