Delayed Environmental Enrichment Reverses Sevoflurane-induced Memory Impairment in Rats

Abstract

Background Anesthesia given to immature rodents causes cognitive decline raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury. Methods 7-day old rats underwent sevoflurane anesthesia (1 MAC, 4 hours) with or without tail clamping. At 4 weeks, rats were randomized to environmental enrichment or normal housing. At 8 weeks rats underwent neurocognitive testing, which consisted of fear conditioning, spatial reference memory and water maze-based memory consolidation tests, that interrogated working memory, short term memory and early long term memory. Results Sevoflurane-treated rats had a greater escape latency when the delay between memory acquisition and memory retrieval was increased from 1 minute to 1 hour, indicating that short term memory was impaired. Delayed environmental enrichment reversed the effects of sevoflurane on short term memory and generally improved many tested aspects of cognitive function, both in sevoflurane-treated and control animals. The performance of tail clamped rats did not differ from those rats receiving anesthesia alone. Conclusion Sevoflurane-induced cognitive decline in rats is treatable. Delayed environmental enrichment rescued the sevoflurane-induced impairment in short-term memory. Tissue injury did not worsen the anesthesia-induced memory impairment. These findings may have relevance to neonatal and pediatric anesthesia.

Early‐life single‐episode sevoflurane exposure impairs social behavior and cognition later in life

“…Previously, two groups conducted learning and memory behavioral tests on neonatal sevo‐treated rats without tail clamping (Shih et al. 2012; Stratmann et al. 2014).…”

“…Long treatment duration indicates potential physiologically intolerable toxicity; this resulted in decreased survival rates from 92% to 67% between the 2 and 4 h (Shih et al. 2012). The present study demonstrated for the first time a single‐episode, 2‐h treatment by sevo alone during the neonatal period impairs both social interaction and cognition.…”

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

“…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). …”

“…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).…”

“…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).…”