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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

Frequency distribution of the strategies used during the MWM test.Panel A: Coding color showing the search strategy used by the Control group (top), H2S group (middle), and H2S-MB group (bottom) (based on coding proposed by Garthe et al. [54]). Of note, is that the two rats in the H2S group unable to swim (#16 and 38, see Table 1) are identified with the dotted line after D2, as they were euthanized at 48 hours. Also in the H2S-MB group, 2 rats, although able to swim were only showing a thigmotaxis pattern during the 4 days of training are identified. Panel B: Radar chart displaying the relative frequency of the various strategies used at D4 by the 3 groups. In the H2S group, the animals used a significantly less effective pattern consisting in higher occurrence of scanning strategy to find the platform when compared to the treated group.
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pone.0131340.g007: Frequency distribution of the strategies used during the MWM test.Panel A: Coding color showing the search strategy used by the Control group (top), H2S group (middle), and H2S-MB group (bottom) (based on coding proposed by Garthe et al. [54]). Of note, is that the two rats in the H2S group unable to swim (#16 and 38, see Table 1) are identified with the dotted line after D2, as they were euthanized at 48 hours. Also in the H2S-MB group, 2 rats, although able to swim were only showing a thigmotaxis pattern during the 4 days of training are identified. Panel B: Radar chart displaying the relative frequency of the various strategies used at D4 by the 3 groups. In the H2S group, the animals used a significantly less effective pattern consisting in higher occurrence of scanning strategy to find the platform when compared to the treated group.

Mentions: In the H2S group, two rats with an obvious motor or visual deficit were unable to swim (Fig 7). All the 7 other rats could swim and their latency to reach platform was not different from the control group averaging 53.7 ± 41.5 sec on the first day (Fig 5). The total swimming distance was 13.4 ± 9.6 m and path efficiency averaged 0.15 ± 0.15, which were similar to the control group, including during the probe trial (Figs 5 and 6). The latency and total distance decreased day by day but this difference was only significant for the distance at D3 and D4, and the path efficiency at D4, due to the large standard deviations.


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)

Frequency distribution of the strategies used during the MWM test.Panel A: Coding color showing the search strategy used by the Control group (top), H2S group (middle), and H2S-MB group (bottom) (based on coding proposed by Garthe et al. [54]). Of note, is that the two rats in the H2S group unable to swim (#16 and 38, see Table 1) are identified with the dotted line after D2, as they were euthanized at 48 hours. Also in the H2S-MB group, 2 rats, although able to swim were only showing a thigmotaxis pattern during the 4 days of training are identified. Panel B: Radar chart displaying the relative frequency of the various strategies used at D4 by the 3 groups. In the H2S group, the animals used a significantly less effective pattern consisting in higher occurrence of scanning strategy to find the platform when compared to the treated group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g007: Frequency distribution of the strategies used during the MWM test.Panel A: Coding color showing the search strategy used by the Control group (top), H2S group (middle), and H2S-MB group (bottom) (based on coding proposed by Garthe et al. [54]). Of note, is that the two rats in the H2S group unable to swim (#16 and 38, see Table 1) are identified with the dotted line after D2, as they were euthanized at 48 hours. Also in the H2S-MB group, 2 rats, although able to swim were only showing a thigmotaxis pattern during the 4 days of training are identified. Panel B: Radar chart displaying the relative frequency of the various strategies used at D4 by the 3 groups. In the H2S group, the animals used a significantly less effective pattern consisting in higher occurrence of scanning strategy to find the platform when compared to the treated group.
Mentions: In the H2S group, two rats with an obvious motor or visual deficit were unable to swim (Fig 7). All the 7 other rats could swim and their latency to reach platform was not different from the control group averaging 53.7 ± 41.5 sec on the first day (Fig 5). The total swimming distance was 13.4 ± 9.6 m and path efficiency averaged 0.15 ± 0.15, which were similar to the control group, including during the probe trial (Figs 5 and 6). The latency and total distance decreased day by day but this difference was only significant for the distance at D3 and D4, and the path efficiency at D4, due to the large standard deviations.

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