Abstract
BackgroundMany studies have reported that sevoflurane can increase neuronal apoptosis and result in cognitive deficits in rodents. Although neurotoxicity may be associated with mitochondrial dysfunction and oxidative stress, the exact mechanism remains unclear. In order to evaluate potential treatment therapies, we studied the effects of hemin on neurotoxicity of neonatal rat sevoflurane exposure.MethodsPostnatal day (P) seven rats were assigned randomly to four groups; (1) group C: non-anesthesia, (2) group H: intraperitoneal hemin (50 mg kg−1) treatment on days 5 and 6, (3) group S: 3% sevoflurane exposure for 4 h, and (4) group SH: hemin treatment + sevoflurane exposure. The expression of neuroglobin in neonatal hippocampus was determined by western blot and immunohistochemistry. Neuroglobin was localized by immunofluorescence. Western blot for the expression of cleaved caspase-3 and TUNEL were used to detect neonatal hippocampal apoptosis, and cytochrome c was used to evaluate mitochondrial function. Drp-1 and Mfn-2 immunoblotting were used to assess mitochondrial dynamics. The Morris water maze test was performed to detect cognitive function in the rats on P30.ResultsExposure to sevoflurane increased the expression of cleaved caspase-3, cytochrome c, and Drp1 in the neonatal hippocampus and resulted in cognitive deficiency but decreased expression of Mfn2. Hemin reduced apoptosis, improved mitochondrial dynamics and ameliorated the cognitive impairment caused by sevoflurane exposure.ConclusionHemin reduced neuronal apoptosis, improved mitochondrial dynamics and protected against cognitive deficits induced by sevoflurane in neonatal rats. This neuroprotective effect may be achieved by increasing the expression of neuroglobin.
Highlights
Every year thousands of infants and young children receive general anesthesia
In this study, we investigated the effect of hemin on mitochondrial dynamic mechanism of sevoflurane neurotoxicity and whether hemin as an inducer of Ngb protects against cognitive dysfunction induced by exposing neonatal rats to sevoflurane
Western blotting was used to detect the expression of cleaved caspase-3 and cytochrome c in the hippocampus of rats to evaluate the effect of sevoflurane on apoptosis in the hippocampus of neonatal rats exposed to 3% sevoflurane for 4 h
Summary
Whether general anesthesia has a detrimental effect on children’s neurodevelopment and cognitive function has attracted much attention in recent years and is controversial (Sun L.S. et al, 2016). Several possibilities have been proposed, including oxidative injury and neuronal apoptosis, the neurotoxic mechanisms remain unclear. Many studies have looked for ways to alleviate the neurotoxicity of neonatal rats caused by exposure to anesthetics (Yonamine et al, 2013; Liao et al, 2014; Pellegrini et al, 2014; Ji et al, 2015; Sun Z. et al, 2016; Perez-Zoghbi et al, 2017; Xia et al, 2017; Xu et al, 2017). In order to evaluate potential treatment therapies, we studied the effects of hemin on neurotoxicity of neonatal rat sevoflurane exposure
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