Abstract
Increasing numbers of children undergo surgery and are exposed to anesthesia that raises concerns regarding the safety of frequently employed anesthetics. Isoflurane, often used in pediatric anesthesia, has been reported to cause neurodegeneration in animal models. The study investigates the effectiveness of pterostilbene on neurodegeneration caused by isoflurane. Separate groups of neonatal mice were administered with pterostilbene at 10, 20 or 40 mg/kg from post natal day 1 (P1) to P15. On P7, rats received isoflurane at 0.75% for 6 hours. Control rats received no anesthesia or pterostilbene. Neuroapoptosis following isoflurane exposure were markedly reduced by pterostilbene , further pterostilbene down-regulated the expre-ssions of caspase-3, Bad, phospho-JNK and phospho-c-Jun and as well improved the expressions of Bcl-xL, JNK, phospho-Bad and phospho-Akt. Pterostilbene enhanced the performance of rats in Morris water maze tests. The observations suggest that pterostilbene was able to effectively reduce isoflurane-induced neurodegeneration.
Highlights
Isoflurane is a commonly used volatile anesthetic in pediatric surgeries (Istaphanous and Loepke, 2009)
Values are represented as mean ± SD, n=6. arepresents statistical significance at p
While anesthetic-induced neurodegeneration has been observed in many brain regions, we focused on hippocampus, as many previous reports have demonstrated that isoflurane-treated neonatal rats present normal short-term memory, a function predominantly involving the prefrontal cortex, but have an abnormal response to contextual fear conditioning, indicating severe hippocampal lesions (Sanders et al, 2009)
Summary
Isoflurane is a commonly used volatile anesthetic in pediatric surgeries (Istaphanous and Loepke, 2009). Prolonged exposure to volatile anesthetics causes neuronal apoptosis and degeneration in develop -ing brains leading to learning and memory deficits (Satomoto et al, 2009; Brambrink et al, 2010; Kong et al, 2011; Li et al, 2013a,b). Recent investigations in children less than 4 years of age, exposed to anaesthesia more than once, present to have greater risks of developing cognitive disabilities (DiMaggio et al, 2011; Ing et al, 2012) raising serious concerns on possible detrimental effects of anesthetics. Isoflurane-induced neuronal apoptosis and degeneration has been observed to occur via JNK pathway and through disruption of intracellular calcium homeostasis and hyperactivation of inositol 1,4,5-trisphosphate (IP3) receptors (Li et al.,2013b; Wei et al, 2008; Yang et al, 2008; Zhao et al, 2011). Isoflurane-induced Ca2+ overload activates mitochondrial apoptosis pathway (Wei et al, 2005; Yon et al, 2005) and causes activation of c-Jun N-terminal kinase (Brambrink et al, 2010)
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