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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

GFAP staining by DAB chromagen with hematoxylin counterstain in one rat exposed to saline (control) and one rat intoxicated with H2S with normal recovery.There was no difference in astrocyte density or morphology between the 2 animals.
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pone.0131340.g012: GFAP staining by DAB chromagen with hematoxylin counterstain in one rat exposed to saline (control) and one rat intoxicated with H2S with normal recovery.There was no difference in astrocyte density or morphology between the 2 animals.

Mentions: For the H2S group, in the 7 rats that presented no clinical deficit, no brain lesions (necrotic or apoptotic neurons) were found (Fig 10A-1, 10B-1 and 10C-1). In contrast, the two rats that had to be euthanized at 48 hours following the NaHS injection due to their inability to eat and persistent motor deficit, presented extensive necrotic lesions consisting in severe bilaterally symmetric, multifocal neuronal necrosis of the superficial and middle laminae of the frontal, parietal, temporal and occipital lobes of the cerebral cortex and cingulate gyrus, with sparing of the deepest laminae (Fig 10A-2, 10B-2 and 10C-2). Neuronal necrosis was also present but more variable in the caudate putamen, amygdala and thalamus (Table 1). The piriform cortex, cerebellar Purkinje cell layer and hippocampal (CA1-3 and dentate gyrus) neuronal populations were completely unaffected. The white matter tracts in the cortex were also unaffected. Examples are shown in Figs 10 and 11, while Table 1 summarizes the location of the various lesions. The brains from all four rats that received H2S, but that displayed no necrotic lesions were negative for cleaved caspase-3. The number of GFAP positive astrocytes and Iba1 positive microglia was not different from the control animals, (Fig 12).


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)

GFAP staining by DAB chromagen with hematoxylin counterstain in one rat exposed to saline (control) and one rat intoxicated with H2S with normal recovery.There was no difference in astrocyte density or morphology between the 2 animals.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131340.g012: GFAP staining by DAB chromagen with hematoxylin counterstain in one rat exposed to saline (control) and one rat intoxicated with H2S with normal recovery.There was no difference in astrocyte density or morphology between the 2 animals.
Mentions: For the H2S group, in the 7 rats that presented no clinical deficit, no brain lesions (necrotic or apoptotic neurons) were found (Fig 10A-1, 10B-1 and 10C-1). In contrast, the two rats that had to be euthanized at 48 hours following the NaHS injection due to their inability to eat and persistent motor deficit, presented extensive necrotic lesions consisting in severe bilaterally symmetric, multifocal neuronal necrosis of the superficial and middle laminae of the frontal, parietal, temporal and occipital lobes of the cerebral cortex and cingulate gyrus, with sparing of the deepest laminae (Fig 10A-2, 10B-2 and 10C-2). Neuronal necrosis was also present but more variable in the caudate putamen, amygdala and thalamus (Table 1). The piriform cortex, cerebellar Purkinje cell layer and hippocampal (CA1-3 and dentate gyrus) neuronal populations were completely unaffected. The white matter tracts in the cortex were also unaffected. Examples are shown in Figs 10 and 11, while Table 1 summarizes the location of the various lesions. The brains from all four rats that received H2S, but that displayed no necrotic lesions were negative for cleaved caspase-3. The number of GFAP positive astrocytes and Iba1 positive microglia was not different from the control animals, (Fig 12).

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