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Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

Sonobe T, Chenuel B, Cooper TK, Haouzi P - PLoS ONE (2015)

Bottom Line: The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals.However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, United States of America.

ABSTRACT

Background: Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.

Methods: NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg i.v.) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7.

Results: Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.

Conclusion: In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

No MeSH data available.


Related in: MedlinePlus

Classification of swimming strategies.A) Schematic drawing of the water maze pool setting showing the location of platform and cues. Animals were placed at either of 3 entries of the pool. The annulus zone and the large circular area around the platform (PTF) were used to identify thigmotaxis, chaining or focal search as previously descried [54]. B) Swimming strategies used by the rats were classified in 8 categories (based on modified criteria proposed by Garthe et al. [54]) and were given a score from 0 to 7. Thigmotaxis, Random search and Scanning are regarded as spatial memory independent, or non-spatial strategies, while Directed, Focal, and Direct search were considered as spatial memory dependent. Chaining was scored separately. A score of 0 was given to the animals unable to swim. The traces are actual swimming patterns observed in our control rats.
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pone.0131340.g001: Classification of swimming strategies.A) Schematic drawing of the water maze pool setting showing the location of platform and cues. Animals were placed at either of 3 entries of the pool. The annulus zone and the large circular area around the platform (PTF) were used to identify thigmotaxis, chaining or focal search as previously descried [54]. B) Swimming strategies used by the rats were classified in 8 categories (based on modified criteria proposed by Garthe et al. [54]) and were given a score from 0 to 7. Thigmotaxis, Random search and Scanning are regarded as spatial memory independent, or non-spatial strategies, while Directed, Focal, and Direct search were considered as spatial memory dependent. Chaining was scored separately. A score of 0 was given to the animals unable to swim. The traces are actual swimming patterns observed in our control rats.

Mentions: Twenty four hours following the episode of NaHS-induced coma, the surviving rats, as well as the control/saline rats, were trained in the reference memory version of the Morris water maze (MWM) task [46–48] to locate a hidden transparent platform (11 cm diameter, 1.5 cm below surface) in a circular pool (1.80 m diameter, 60 cm height). The room was equipped with four extra-maze cues (60 × 70 cm) located on the four directions (S, N, E, W) behind the maze’s wall, to facilitate spatial learning. Water was kept at a temperature of 19–20°C. Each rat was given 4 trials per day for 4 consecutive days with an inter-trial interval of 10 min. Platform position remained constant throughout the study and was located in the SW quadrant (Fig 1). Rats were released from one of three other quadrants and allowed to search the platform up to 120 s. Every day, the starting position was changed in a random manner. On the first day, rats that did not find the platform were guided to the platform and were allowed to remain there for at least 30 sec. Swim paths of each animal on each trial were recorded using a ceiling-mounted digital camera and ANY-maze video tracking software (version 4.99, ANY-maze, Stoelting Co., Wood Dale, IL) for further analysis. On the last day, the fourth trial was replaced by a 120 s probe trial, i.e. with the platform removed. The probe trial provides a measure of retention, which is determined by time and distance swum to reach the site where the platform had been located and the amount of time spent in the enlarged platform area [49].


Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

Sonobe T, Chenuel B, Cooper TK, Haouzi P - PLoS ONE (2015)

Classification of swimming strategies.A) Schematic drawing of the water maze pool setting showing the location of platform and cues. Animals were placed at either of 3 entries of the pool. The annulus zone and the large circular area around the platform (PTF) were used to identify thigmotaxis, chaining or focal search as previously descried [54]. B) Swimming strategies used by the rats were classified in 8 categories (based on modified criteria proposed by Garthe et al. [54]) and were given a score from 0 to 7. Thigmotaxis, Random search and Scanning are regarded as spatial memory independent, or non-spatial strategies, while Directed, Focal, and Direct search were considered as spatial memory dependent. Chaining was scored separately. A score of 0 was given to the animals unable to swim. The traces are actual swimming patterns observed in our control rats.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482667&req=5

pone.0131340.g001: Classification of swimming strategies.A) Schematic drawing of the water maze pool setting showing the location of platform and cues. Animals were placed at either of 3 entries of the pool. The annulus zone and the large circular area around the platform (PTF) were used to identify thigmotaxis, chaining or focal search as previously descried [54]. B) Swimming strategies used by the rats were classified in 8 categories (based on modified criteria proposed by Garthe et al. [54]) and were given a score from 0 to 7. Thigmotaxis, Random search and Scanning are regarded as spatial memory independent, or non-spatial strategies, while Directed, Focal, and Direct search were considered as spatial memory dependent. Chaining was scored separately. A score of 0 was given to the animals unable to swim. The traces are actual swimming patterns observed in our control rats.
Mentions: Twenty four hours following the episode of NaHS-induced coma, the surviving rats, as well as the control/saline rats, were trained in the reference memory version of the Morris water maze (MWM) task [46–48] to locate a hidden transparent platform (11 cm diameter, 1.5 cm below surface) in a circular pool (1.80 m diameter, 60 cm height). The room was equipped with four extra-maze cues (60 × 70 cm) located on the four directions (S, N, E, W) behind the maze’s wall, to facilitate spatial learning. Water was kept at a temperature of 19–20°C. Each rat was given 4 trials per day for 4 consecutive days with an inter-trial interval of 10 min. Platform position remained constant throughout the study and was located in the SW quadrant (Fig 1). Rats were released from one of three other quadrants and allowed to search the platform up to 120 s. Every day, the starting position was changed in a random manner. On the first day, rats that did not find the platform were guided to the platform and were allowed to remain there for at least 30 sec. Swim paths of each animal on each trial were recorded using a ceiling-mounted digital camera and ANY-maze video tracking software (version 4.99, ANY-maze, Stoelting Co., Wood Dale, IL) for further analysis. On the last day, the fourth trial was replaced by a 120 s probe trial, i.e. with the platform removed. The probe trial provides a measure of retention, which is determined by time and distance swum to reach the site where the platform had been located and the amount of time spent in the enlarged platform area [49].

Bottom Line: The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals.However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, United States of America.

ABSTRACT

Background: Acute hydrogen sulfide (H2S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity.

Methods: NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg i.v.) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7.

Results: Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.

Conclusion: In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.

No MeSH data available.


Related in: MedlinePlus