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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

Average swimming strategy score in all the intoxicated rats with and without brain lesions following H2S induced coma in non-treated animals (red symbols) and in animals receiving MB (blue symbols).The swimming strategy was scored according to the swimming pattern described in the Fig 1 (the rats unable to swim were scored as zero), the score was averaged over the last 2 days of training. The score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (*P<0.01, see text for further details). The ID numbers of the rats presenting with brain lesions (corresponding to the ID numbers in Table 1) are shown. In all rats but one, lesions were highly predictable from the clinical picture.
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pone.0131340.g014: Average swimming strategy score in all the intoxicated rats with and without brain lesions following H2S induced coma in non-treated animals (red symbols) and in animals receiving MB (blue symbols).The swimming strategy was scored according to the swimming pattern described in the Fig 1 (the rats unable to swim were scored as zero), the score was averaged over the last 2 days of training. The score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (*P<0.01, see text for further details). The ID numbers of the rats presenting with brain lesions (corresponding to the ID numbers in Table 1) are shown. In all rats but one, lesions were highly predictable from the clinical picture.

Mentions: Swimming strategies were scored according to the swimming pattern presented in Fig 1 (from 0 unable to swim to 7 direct swimming). The scores were averaged over the trials performed in the last 2 days. The 13 rats with no brain lesions scored 4.9 ± 0.8, while the 5 rats with severe brain lesions displayed an average score of 1.3 ± 1.9 (Fig 14). Finally, the score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (5.6 ± 0.7 versus 4.4 ± 0.5, P<0.01).


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)

Average swimming strategy score in all the intoxicated rats with and without brain lesions following H2S induced coma in non-treated animals (red symbols) and in animals receiving MB (blue symbols).The swimming strategy was scored according to the swimming pattern described in the Fig 1 (the rats unable to swim were scored as zero), the score was averaged over the last 2 days of training. The score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (*P<0.01, see text for further details). The ID numbers of the rats presenting with brain lesions (corresponding to the ID numbers in Table 1) are shown. In all rats but one, lesions were highly predictable from the clinical picture.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g014: Average swimming strategy score in all the intoxicated rats with and without brain lesions following H2S induced coma in non-treated animals (red symbols) and in animals receiving MB (blue symbols).The swimming strategy was scored according to the swimming pattern described in the Fig 1 (the rats unable to swim were scored as zero), the score was averaged over the last 2 days of training. The score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (*P<0.01, see text for further details). The ID numbers of the rats presenting with brain lesions (corresponding to the ID numbers in Table 1) are shown. In all rats but one, lesions were highly predictable from the clinical picture.
Mentions: Swimming strategies were scored according to the swimming pattern presented in Fig 1 (from 0 unable to swim to 7 direct swimming). The scores were averaged over the trials performed in the last 2 days. The 13 rats with no brain lesions scored 4.9 ± 0.8, while the 5 rats with severe brain lesions displayed an average score of 1.3 ± 1.9 (Fig 14). Finally, the score of the rats reaching the platform was significantly higher in the treated group than in the non-treated animals (5.6 ± 0.7 versus 4.4 ± 0.5, P<0.01).

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