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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

Experimental design and outcomes.Twenty-one control rats received saline IP injection and were assigned to behavior test (control rats). A first series of 32 rats received H2S injection, 8 rats did not present a coma. The 24 rats that presented a coma, were separated into a non-treatment (H2S) group (12 rats) and methylene blue treated (H2S-MB) group (12 rats). In the H2S group, 8 died immediately (*1 out of 8 rats died within 12 h) and 4 survived from a coma (one these 4 rats was however unable to swim). Meanwhile 9 survived in the H2S-MB group, they were all able to swim. Therefore, to match the number of surviving rats between the 2 groups, a second series of 10 rats received NaHS: 5 died and 5 survived. The 5 surviving rats were added to the H2S group, one of them could not swim. Out of 9 surviving rats in the H2S group, 7 could therefore complete the behavior test, while the 2 rats unable to swim were euthanized within 48 h. Out of 9 surviving rats in the H2S-MB group, 9 completed the behavior test.
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pone.0131340.g002: Experimental design and outcomes.Twenty-one control rats received saline IP injection and were assigned to behavior test (control rats). A first series of 32 rats received H2S injection, 8 rats did not present a coma. The 24 rats that presented a coma, were separated into a non-treatment (H2S) group (12 rats) and methylene blue treated (H2S-MB) group (12 rats). In the H2S group, 8 died immediately (*1 out of 8 rats died within 12 h) and 4 survived from a coma (one these 4 rats was however unable to swim). Meanwhile 9 survived in the H2S-MB group, they were all able to swim. Therefore, to match the number of surviving rats between the 2 groups, a second series of 10 rats received NaHS: 5 died and 5 survived. The 5 surviving rats were added to the H2S group, one of them could not swim. Out of 9 surviving rats in the H2S group, 7 could therefore complete the behavior test, while the 2 rats unable to swim were euthanized within 48 h. Out of 9 surviving rats in the H2S-MB group, 9 completed the behavior test.

Mentions: The overall immediate outcomes are displayed in Fig 2.


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)

Experimental design and outcomes.Twenty-one control rats received saline IP injection and were assigned to behavior test (control rats). A first series of 32 rats received H2S injection, 8 rats did not present a coma. The 24 rats that presented a coma, were separated into a non-treatment (H2S) group (12 rats) and methylene blue treated (H2S-MB) group (12 rats). In the H2S group, 8 died immediately (*1 out of 8 rats died within 12 h) and 4 survived from a coma (one these 4 rats was however unable to swim). Meanwhile 9 survived in the H2S-MB group, they were all able to swim. Therefore, to match the number of surviving rats between the 2 groups, a second series of 10 rats received NaHS: 5 died and 5 survived. The 5 surviving rats were added to the H2S group, one of them could not swim. Out of 9 surviving rats in the H2S group, 7 could therefore complete the behavior test, while the 2 rats unable to swim were euthanized within 48 h. Out of 9 surviving rats in the H2S-MB group, 9 completed the behavior test.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g002: Experimental design and outcomes.Twenty-one control rats received saline IP injection and were assigned to behavior test (control rats). A first series of 32 rats received H2S injection, 8 rats did not present a coma. The 24 rats that presented a coma, were separated into a non-treatment (H2S) group (12 rats) and methylene blue treated (H2S-MB) group (12 rats). In the H2S group, 8 died immediately (*1 out of 8 rats died within 12 h) and 4 survived from a coma (one these 4 rats was however unable to swim). Meanwhile 9 survived in the H2S-MB group, they were all able to swim. Therefore, to match the number of surviving rats between the 2 groups, a second series of 10 rats received NaHS: 5 died and 5 survived. The 5 surviving rats were added to the H2S group, one of them could not swim. Out of 9 surviving rats in the H2S group, 7 could therefore complete the behavior test, while the 2 rats unable to swim were euthanized within 48 h. Out of 9 surviving rats in the H2S-MB group, 9 completed the behavior test.
Mentions: The overall immediate outcomes are displayed in Fig 2.

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