Effects of vitamin C on inhalation anesthetic isoflurane-induced developmental, neuronal apoptosis in neonatal rats

Abstract

Research ArticleEffects of vitamin C on inhalation anesthetic isoflurane-induced developmental, neuronal apoptosis in neonatal rats BJP IntroductionAbout 200 million patients worldwide are exposed to anesthesia and undergo surgery each year (Weiser et al., 2008;Moonesinghe et al., 2011). Volatile anesthetics such as isoflurane and sevoflurane are used in millions of young children each year during surgical procedures and imaging studies (Istaphanous and Loepke, 2009). Exposure to anesthetic cocktails (Yon et al., 2005;Lu et al., 2006;Sanders et al., 2009) or volatile agents such as isoflurane even as a single anesthetic (Yon et al., 2005;Ma et al., 2007) has been reported to be associated with widespread apoptotic neurodegeneration in the developing brains and contributes to the post-operative cognitive dysfunction (POCD) (Jevtovic-Todorovic et al., 2003;Satomoto et al., 2009;Brambrink et al., 2010;Kong et al., 2011;Paule et al., 2011; Li et al., 2013a,b).In rodent models, the effects of anesthesia have been evaluated following exposure during a time of peak brain development and synaptogenesis, typically at postnatal day 7 (P7) (Jevtovic-Todorovic et al., 2003;Stratmann et al., 2009b;Shih et al., 2012). Apoptosis has been observed to occur acutely in the period immediately following anesthesia (Jevtovic-Todorovic et al., 2003;Istaphanous et al., 2011;Shih et al., 2012), and the thalamus and hippocampus are known areas susceptible to extensive neurodegeneration (JevtovicTodorovic et al., 2003;Satomoto et al., 2009;Shih et al., 2012). AbstractDevelopmental abnormalities, neuronal apoptosis and associated cognitive impairment following isoflurane exposure in neonatal rodents have been reported. The study was undertaken to investigate the effect of vitamin C supplementation against isoflurane-induced neurotoxicity. Seven day old rats were exposed to 1.1% isoflurane, or air for 6 hours. Treatment groups were administered with vitamin C (30 mg/kg, orally) from postnatal day 1 (P1) to P10 and were exposed to isoflurane on P7. Isoflurane exposure induced apoptosis was determined by Fluoro-Jade C and terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay. Vitamin C considerably improved memory and learning impairments, modulated neuroapoptosis and improved expressions of brain-derived neurotrophic factor, nerve growth factor, Bcl-xL and decreased activated caspase-3 expressions. Thus, vitamin C effectively offered protection against isoflurane-induced neuronal apoptosis, learning and memory disturbances. Article Info