The Role Of Melatonnin In Neurogenic Pulmonary Edema After Subarachnoid Hemorrhage In Rats

PurposeNeurogenic pulmonary edema (NPE) is a serious non-neurological complication that can occur after a subarachnoid hemorrhage (SAH) and is associated with decreased survival and a poor neurological outcome. Melatonin is a strong antioxidant that has beneficial effects against SAH in rats, including reduced mortality and reduced neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model, however, have not been clearly identified. This study was undertaken to determine the influence of melatonin on SAH-induced NPE and the potential mechanism of these effects.MethodsSeventy-five Sprague-Dawley rats were randomly divided into sham+vehicle, SAH+melatonin, and SAH+vehicle groups. The SAH model was induced by endovascular perforation. After 24 h of SAH, the amount of the NPE criteria, Lung Histopathology and TUNEL staining assay, lung water content, and expression of MPO,Caspase-1, IL-l?, MMP 9, ZO-1, Occludin, cleaved caspase-3 in all groups were assayed. Mortality and neurological scores were recorded after 24 h of SAH.ResultsCompared with the sham+vehicle group, the SAH+vehicle group animals have significantly upregulated expressions of MMP 9, ZO-1, Occludin and MPO,Caspase-1, IL-1?,cleaved caspase-3, in addition to the increased cell apoptosis, alveolar-capillary barrier dysfunctions, neutrophilic infiltration, lung edema and neurological function deficit. Treatment with melatonin suppressed the expression of MMP 9, ZO-1, Occludin and MPO, Caspase-1, IL-1?, cleaved caspase-3 and reduced cell apoptosis, neutrophilic infiltration, lung edema and neurological function deficit.ConclusionTaken together, these findings show that administration of melatonin attenuates NPE by preventing alveolar-capillary barrier dysfunctions via repressing the inflammatory response and by anti-apoptosis effects after SAH..