Sarin-induced neuropathology in rats

Kadar, Tamar; Shapira, Shlomo; Cohen, Giora; Sahar, Rita; Alkalay, David; Raveh, Lily

doi:10.1177/096032719501400304

Cited by 112 publications

(64 citation statements)

References 14 publications

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“…This idea, however, requires further testing, including histopathological studies to determine that memory deficits can be correlated to damage, specifically in the hippocampus. Previous studies in rats [29], in Gulf War Veterans [30,31] and in victims of the Tokyo subway sarin attack [2] have demonstrated that a single exposure to sarin results in reduced volumes of specific hippocampal areas, supporting the idea that the memory deficits in our rats is likely due to structural changes in the hippocampus. DFP was used in this investigation due to its similarity to sarin, which has greater volatility and has been used as both a military nerve gas and in terrorist attacks.…”

Section: Discussionsupporting

confidence: 82%

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

2015

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Humans and rats poisoned with sarin develop chronic neurological disabilities that are not prevented with standardized antidotal therapy. We hypothesized that rats poisoned with the sarin analogue diisopropylfluorophosphate (DFP) and resuscitated with atropine and pralidoxime would have long-term memory deficits that were preventable with naltrexone treatment. Long Evans rats (250-275 g) were randomized to: DFP (N=8): single subcutaneous (SC) injection of DFP (5 mg/kg). Treatment (N=9): DFP (5 mg/kg) followed by chronic naltrexone (5 mg/kg/day × 12 weeks). Control (N= 12): single SC injection of isopropyl alcohol, (DFP vehicle) followed by chronic naltrexone (5 mg/kg/day). If toxicity developed after injection, antidotal therapy was initiated with atropine (2 mg/kg) and pralidoxime (25 mg/kg) and repeated as needed. After 12 weeks, rats underwent testing for place learning (acquisition) across 5 days of training using the Morris Water Maze. On day 6 a memory retention test was performed. Statistical analysis was performed using IBM SPSS Statistics. Rats receiving DFP rapidly developed toxicity requiring antidotal rescue. No differences in acquisition were seen between the DFP vs. DFP+naltrexone rats. During memory testing, DFP-poisoned rats spent significantly less time (29.4±2.11 versus 38.5±2.5 s, p<0.05) and traveled less distance (267±24.6 versus 370±27.5 cm, p<0.05) in the target quadrant compared to the treatment group. Treatment rats performed as well as control rats (p>0.05) on the test for memory retention. Poisoning with DFP induced impaired memory retention. Deficits were not prevented by acute rescue with atropine and pralidoxime. Chronic naltrexone treatment led to preserved memory after DFP poisoning.

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Section: Discussionsupporting

confidence: 82%

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

2015

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“…This agent immediately and strongly inhibits acetylcholinesterase activity, and causes disturbances of autonomic transmission at the muscarinic and nicotinic acetylcholine receptors 1) . In Japan, we have experienced two terrorist attacks with sarin.…”

mentioning

confidence: 99%

Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack

Miyaki

Nishiwaki

Maekawa

et al. 2005

Journal of Occupational Health

133

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Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack: Koichi MIYAKI, et al. Department of Preventive Medicine and PublicHealth, School of Medicine, Keio University-This study was designed to assess the after effects of sarin exposure on the nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20 March, 1995. We performed a similar study 3 yr after the disaster. This time, we newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power. New subjects consisted of 23 male exposed subjects and 13 referent subjects matched for age and working types. Neurobehavioral tests for psychomotor function and memory, stabilometry, and Benton visual retention test were performed. As reported previously, the exposed group performed significantly less well in the psychomotor function test (tapping) than the referent group (117.8 ± 1.2 vs. 105.6 ± 1.2 msec). Using merged data, this phenomenon was also observed in a dose-dependent manner and the exposed group performed significantly less well in the backward digit span test (4.47 ± 1.17 vs. 5.11 ± 1.65 digits). These results indicate that chronic decline of psychomotor function and memory function still exist 7 yr after the sarin exposure. (J Occup Health 2005; 47: 299-304)

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“…Changes were more pronounced in the cerebral cortex with the formation of vacuoles due to the aggregation of cytoplasm in rat pretreated with Bocopa monnieri followed by acephate. Kedar et al [31] observed lesions with dose of sarin in the hippocampus, pyriform cortex and thalamus of rat. They further, observed significant decline in the area of CA1 and CA3 hippocampal cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Potential of Acephate and Ethanol Extract of Bacopa Monnieri on AChE in Rat Cortex and Hippocampus

Tembhre¹,

Ahirwar²,

Gour³

et al. 2015

IJBBB

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Abstract:The objective of present study was to evaluate the in vivo effect of Bacopa monnieri leaf extract (100 mg/kg) and acephate (37.8 mg/kg) on Acetylcholinesterase (AChE) activity, kinetics and histology of cerebral cortex and hippocampus of brain of male albino rat. AChE activity was measured spectrophotometrically according to the method of Ellman et al.. The acephate inhibited AChE activity strongly in cerebral cortex (72.5%; P < 0.02) than in hippocampus (55.6%; P < 0.02). Bacopa monnieri similarly elicited higher AChE inhibition in cerebral cortex (51.6%; P < 0.05) than in hippocampus (38%; P < 0.01). However, synergistic inhibitory effect was recorded in rats pretreated with Bacopa monnieri followed by acephate exposure. Kinetic study of treated groups demonstrated competitive AChE inhibition in the brain regions, which was evident by increased Km and unchanged Vmax values against the control group. The histopathological examinations showed degeneration of pyramidal cells, deformity of neurocytes and vacuole formation in cytoplasm. These changes were pronounced with acephate. Our result shows that Bacopa monnieri has anti-cholinesterase potential hence it could provide novel pharmacological leads of potential benefit to the treatment of Alzheimer's disease and therefore warrant further investigation.

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Sarin-induced neuropathology in rats

Cited by 112 publications

References 14 publications

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack

Inhibitory Potential of Acephate and Ethanol Extract of Bacopa Monnieri on AChE in Rat Cortex and Hippocampus

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