Inhaled Methane Protects Rats Against Neurological Dysfunction Induced by Cerebral Ischemia and Reperfusion Injury: PI3K/Akt/HO-1 Pathway Involved.

BACKGROUND AND AIMS

Cerebral ischemia and reperfusion (I/R) could produce excess reactive oxygen species (ROS), which in turn induce neurological dysfunction and inflammation in cerebral tissues. This study was designed to study the effect of methane on cerebral I/R injury.

METHODS

Fifty Sprague-Dawley (SD) rats were used to induce an animal model of cerebral I/R injury. Methane was mixed with air to achieve a final concentration of 2.2%. Rats started to inhale methane-air mixture after ischemia and continued it during the reperfusion. The neurological deficits, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the brain tissue were examined. The protein kinase B (Akt) phosphorylation and heme oxygenase-1 (HO-1) expression was measured by Western Blot. The neurological deficits were re-measured after rats were treated with the HO-1 inhibitor Zinc protoporphyrin IX (ZnPP-IX), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine.

RESULTS

Cerebral I/R induced neurological deficit, which was significantly decreased by methane. MDA and TNF-α levels were significantly enhanced by cerebral I/R, while methane caused significant reduction of MDA and TNF-α levels. Methane significantly increased Akt phosphorylation and HO-1 expression. The HO-1 inhibitor ZnPP-IX, PI3K inhibitor LY294002 and Akt inhibitor triciribine all significantly abolished the effect of methane on neurological deficit.

CONCLUSIONS

This finding suggests the possible application of methane for cerebral I/R injury and PI3K/Akt/HO-1 dependent antioxidant pathway may be involved.