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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

Daily evolution of the spatial dependent and non-dependent strategies used during the MWM test.Data of the Control group (top), H2S group (middle), and H2S-MB group (bottom) are displayed. All groups showed a progression towards more spatial patterns during the training phase, but spatial strategy was used much less often in the H2S group.
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pone.0131340.g008: Daily evolution of the spatial dependent and non-dependent strategies used during the MWM test.Data of the Control group (top), H2S group (middle), and H2S-MB group (bottom) are displayed. All groups showed a progression towards more spatial patterns during the training phase, but spatial strategy was used much less often in the H2S group.

Mentions: In the H2S groups, the rats showed typical thigmotaxis swimming pattern on the 1st day of training, like the control group. Spatial strategies were used in 11% of trial at D1 and in 54% of trials at D4 of the rats able to swim, when the analysis included all the rats that received H2S, comprising the rats unable to swim as one of the pattern of responses (zero score), only 42% of the rats exposed to H2S and surviving the coma were actually able to find a platform using a spatial strategy (Figs 7 and 8) at D4 (P<0.01, by Fisher’s exact test). In addition, the H2S exposed rats showed a clear preference for scanning (33% of trials) at D4 in contrast to 16% in the control group (P<0.01, by Fisher’s exact test). Finally, in major contrast to the control group, direct search was used in only 11% of trials in the H2S group.


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)

Daily evolution of the spatial dependent and non-dependent strategies used during the MWM test.Data of the Control group (top), H2S group (middle), and H2S-MB group (bottom) are displayed. All groups showed a progression towards more spatial patterns during the training phase, but spatial strategy was used much less often in the H2S group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g008: Daily evolution of the spatial dependent and non-dependent strategies used during the MWM test.Data of the Control group (top), H2S group (middle), and H2S-MB group (bottom) are displayed. All groups showed a progression towards more spatial patterns during the training phase, but spatial strategy was used much less often in the H2S group.
Mentions: In the H2S groups, the rats showed typical thigmotaxis swimming pattern on the 1st day of training, like the control group. Spatial strategies were used in 11% of trial at D1 and in 54% of trials at D4 of the rats able to swim, when the analysis included all the rats that received H2S, comprising the rats unable to swim as one of the pattern of responses (zero score), only 42% of the rats exposed to H2S and surviving the coma were actually able to find a platform using a spatial strategy (Figs 7 and 8) at D4 (P<0.01, by Fisher’s exact test). In addition, the H2S exposed rats showed a clear preference for scanning (33% of trials) at D4 in contrast to 16% in the control group (P<0.01, by Fisher’s exact test). Finally, in major contrast to the control group, direct search was used in only 11% of trials in the H2S group.

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