Intranasal Administration of Insulin Reduces Chronic Behavioral Abnormality and Neuronal Apoptosis Induced by General Anesthesia in Neonatal Mice

Autor: Fei Liu, Jian Li, Qian Yu, Khalid Iqbal, Chun-ling Dai, Hengchang Li, Shengwei Peng, Jin-hua Gu, Cheng-Xin Gong
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Neuroscience, Vol 13 (2019)
Frontiers in Neuroscience
DOI: 10.3389/fnins.2019.00706/full
Popis: Children, after multiple exposures to general anesthesia, appear to be at an increased risk of developing learning disabilities. Almost all general anesthetics-including sevoflurane, which is commonly used for children-are potentially neurotoxic to the developing brain. Anesthesia exposure during development might also be associated with behavioral deficiencies later in life. To date, there is no treatment to prevent anesthesia-induced neurotoxicity and behavioral changes. In this study, we anesthetized 7-day-old neonatal mice with sevoflurane for 3 h per day for three consecutive days and found that the anesthesia led to mild behavioral abnormalities later in life that were detectable by using the novel object recognition test, Morris water maze, and fear conditioning test. Biochemical and immunohistochemical studies indicate that anesthesia induced a decrease in brain levels of postsynaptic density 95 (PSD95), a postsynaptic marker, and marked activation of neuronal apoptosis in neonatal mice. Importantly, insulin administered through intranasal delivery prior to anesthesia was found to prevent the anesthesia-induced long-term behavioral abnormalities, reduction of PSD95, and activation of neuronal apoptosis. These findings suggest that intranasal insulin administration could be an effective approach to prevent the increased risk of neurotoxicity and chronic damage caused by anesthesia in the developing brain.
Databáze: OpenAIRE