Magnetic resonance imaging reveals that galantamine prevents structural brain damage induced by an acute exposure of guinea pigs to soman

• Published in: Neurotoxicology (Park Forest South) Vol. 31; no. 1; pp. 67 - 76
• Main Authors: Gullapalli, Rao P., Aracava, Yasco, Zhuo, Jiachen, Neto, Edward Helal, Wang, Jiazheng, Makris, George, Merchenthaler, Istvan, Pereira, Edna F.R., Albuquerque, Edson X.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 2010; Elsevier
• Subjects: Alzheimer's disease; Animals; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain Mapping; Chemical and industrial products toxicology. Toxic occupational diseases; Cholinesterase Inhibitors - toxicity; Dose-Response Relationship, Drug; Female; Galantamine; Galantamine - therapeutic use; Gas, fumes; Gene Expression Regulation - drug effects; Guinea Pigs; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medical sciences; Neurodegeneration; Neurogranin - genetics; Neurogranin - metabolism; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - prevention & control; Nootropic Agents - therapeutic use; Organophosphorus compounds; RNA, Messenger - metabolism; Soman - toxicity; Time Factors; Toxicology; Organophosphorus compounds; Magnetic resonance imaging; Galantamine; Neurodegeneration; Guinea pigs; Benzazepine derivatives; Esterases; Acetylcholinesterase; Prevention; Chemical warfare agent; Alkaloid; Guinea pig; Anticholinesterase agent; Soman; Toxic gas; Nervous system diseases; Enzyme; Acute; Rodentia; Enzyme inhibitor; Exposure; Antialzheimer agent; Nuclear magnetic resonance imaging; Carboxylic ester hydrolases; Parasympathomimetic; Cerebral disorder; Vertebrata; Mammalia; Animal; Central nervous system disease; Hydrolases
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2009.09.004

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 μg/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 7 h 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.