Limits...
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

Body weight following H2S induced coma.Body weight decreased gradually over the 4 days of training in the control group. In the H2S group, body weight significantly dropped at D1 day (significantly different from control group, P<0.05), and then did not change thereafter. Note that the 2 rats unable to eat that were euthanized are not included in this computation. In the H2S-MB group, weight also significantly dropped at D1 (significantly different from control group, P<0.05) then remained below baseline until D4. Values are shown as mean ± SD. *significantly different from control at P<0.05. # Significantly different from baseline (day 0) at P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482667&req=5

pone.0131340.g004: Body weight following H2S induced coma.Body weight decreased gradually over the 4 days of training in the control group. In the H2S group, body weight significantly dropped at D1 day (significantly different from control group, P<0.05), and then did not change thereafter. Note that the 2 rats unable to eat that were euthanized are not included in this computation. In the H2S-MB group, weight also significantly dropped at D1 (significantly different from control group, P<0.05) then remained below baseline until D4. Values are shown as mean ± SD. *significantly different from control at P<0.05. # Significantly different from baseline (day 0) at P<0.05.

Mentions: The three groups of rats had a weight that was not significantly different at baseline. The weight of the surviving rats of the H2S group, that were able to swim, decreased from 471 ± 106 g to 457 ± 99 g at D1 (-2.6 ± 2.2% of the initial body weight, P<0.05 vs baseline and versus control group, Fig 4). The body weight of the 9 surviving rats in the H2S-MB group also decreased from 459 ± 52 g to 447 ± 51 g at D1 (-2.7 ± 1.6% of the initial body weight, P<0.05 vs baseline and vs control group, Fig 4). There was no further significant loss of weight after that. Of note is that the 21 rats that were used as control receiving saline injection (4 ml/kg, IP) displayed a light but significant progressive decrease in body weight from 484 ± 81 g to 476 ± 75 g at D4 of MWM testing (P<0.01, Fig 4).


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)

Body weight following H2S induced coma.Body weight decreased gradually over the 4 days of training in the control group. In the H2S group, body weight significantly dropped at D1 day (significantly different from control group, P<0.05), and then did not change thereafter. Note that the 2 rats unable to eat that were euthanized are not included in this computation. In the H2S-MB group, weight also significantly dropped at D1 (significantly different from control group, P<0.05) then remained below baseline until D4. Values are shown as mean ± SD. *significantly different from control at P<0.05. # Significantly different from baseline (day 0) at P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g004: Body weight following H2S induced coma.Body weight decreased gradually over the 4 days of training in the control group. In the H2S group, body weight significantly dropped at D1 day (significantly different from control group, P<0.05), and then did not change thereafter. Note that the 2 rats unable to eat that were euthanized are not included in this computation. In the H2S-MB group, weight also significantly dropped at D1 (significantly different from control group, P<0.05) then remained below baseline until D4. Values are shown as mean ± SD. *significantly different from control at P<0.05. # Significantly different from baseline (day 0) at P<0.05.
Mentions: The three groups of rats had a weight that was not significantly different at baseline. The weight of the surviving rats of the H2S group, that were able to swim, decreased from 471 ± 106 g to 457 ± 99 g at D1 (-2.6 ± 2.2% of the initial body weight, P<0.05 vs baseline and versus control group, Fig 4). The body weight of the 9 surviving rats in the H2S-MB group also decreased from 459 ± 52 g to 447 ± 51 g at D1 (-2.7 ± 1.6% of the initial body weight, P<0.05 vs baseline and vs control group, Fig 4). There was no further significant loss of weight after that. Of note is that the 21 rats that were used as control receiving saline injection (4 ml/kg, IP) displayed a light but significant progressive decrease in body weight from 484 ± 81 g to 476 ± 75 g at D4 of MWM testing (P<0.01, Fig 4).

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