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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

Examples of swimming strategies in 2 intoxicated rats treat with MB.The recordings in the upper panels where obtained from a rat with no brain lesions while those in the lower panels were obtained in the rat #92, (Table 1) that was later found to have neuronal cortical necrosis. The latter rat was unable to find the platform even though its behavior was normal during open field test.
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pone.0131340.g009: Examples of swimming strategies in 2 intoxicated rats treat with MB.The recordings in the upper panels where obtained from a rat with no brain lesions while those in the lower panels were obtained in the rat #92, (Table 1) that was later found to have neuronal cortical necrosis. The latter rat was unable to find the platform even though its behavior was normal during open field test.

Mentions: In the H2S-MB group, two rats that could not find the platform at D1 and D2 were still unable to find the platform and to engage into any search strategy at the end of the 4th day. These 2 rats also displayed on a few occasions irregular spiral (repetitive looping) swimming patterns (Fig 9). The 7 remaining rats that could find the platform used spatial strategies with a significantly higher occurrence than in the H2S group; even after including the animals unable to find the platform, these strategies were present in 69% of trials at D4 (P<0.05 vs H2S group). When all the surviving animals were included, the rats presented 19% of direct, 30% of focal, and 19% of directed swimming strategy as spatial memory-dependent strategies during the 4th day, and only 4% of scanning swimming strategy (Fig 7), which was the most frequently used in the H2S group (P<0.0001).


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)

Examples of swimming strategies in 2 intoxicated rats treat with MB.The recordings in the upper panels where obtained from a rat with no brain lesions while those in the lower panels were obtained in the rat #92, (Table 1) that was later found to have neuronal cortical necrosis. The latter rat was unable to find the platform even though its behavior was normal during open field test.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g009: Examples of swimming strategies in 2 intoxicated rats treat with MB.The recordings in the upper panels where obtained from a rat with no brain lesions while those in the lower panels were obtained in the rat #92, (Table 1) that was later found to have neuronal cortical necrosis. The latter rat was unable to find the platform even though its behavior was normal during open field test.
Mentions: In the H2S-MB group, two rats that could not find the platform at D1 and D2 were still unable to find the platform and to engage into any search strategy at the end of the 4th day. These 2 rats also displayed on a few occasions irregular spiral (repetitive looping) swimming patterns (Fig 9). The 7 remaining rats that could find the platform used spatial strategies with a significantly higher occurrence than in the H2S group; even after including the animals unable to find the platform, these strategies were present in 69% of trials at D4 (P<0.05 vs H2S group). When all the surviving animals were included, the rats presented 19% of direct, 30% of focal, and 19% of directed swimming strategy as spatial memory-dependent strategies during the 4th day, and only 4% of scanning swimming strategy (Fig 7), which was the most frequently used in the H2S group (P<0.0001).

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