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Updated: Jan 21, 2026

Intranasal Administration of CNS Therapeutics to Awake Mice
Published on: April 8, 2013
Intranasal Administration of Insulin Reduces Chronic Behavioral Abnormality and Neuronal Apoptosis Induced by General
Hengchang Li1,2, Chun-Ling Dai1, Jin-Hua Gu1,3
1Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, United States.
Insights
General anesthesia may harm developing brains, causing learning and behavioral issues. Intranasal insulin prevented these anesthesia-induced neurotoxic effects in neonatal mice, offering a potential protective strategy.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Repeated exposure to general anesthetics, like sevoflurane, poses a neurotoxic risk to the developing brain.
- Anesthesia during critical developmental periods may lead to long-term learning disabilities and behavioral deficits.
- Currently, no established treatments exist to prevent anesthesia-induced neurotoxicity in children.
Purpose of the Study:
- To investigate the long-term behavioral and neurobiological consequences of sevoflurane anesthesia in neonatal mice.
- To evaluate the potential of intranasal insulin administration as a protective intervention against anesthesia-induced neurotoxicity.
Main Methods:
- Neonatal mice (postnatal day 7) were exposed to sevoflurane anesthesia for 3 hours daily over three consecutive days.
- Behavioral assessments included novel object recognition, Morris water maze, and fear conditioning tests.
- Biochemical and immunohistochemical analyses measured postsynaptic density 95 (PSD95) levels and neuronal apoptosis.
Main Results:
- Sevoflurane anesthesia induced mild, long-term behavioral abnormalities in neonatal mice.
- Anesthesia exposure led to decreased brain PSD95 levels and increased neuronal apoptosis.
- Intranasal insulin administration prior to anesthesia prevented behavioral deficits, PSD95 reduction, and apoptosis.
Conclusions:
- Sevoflurane anesthesia causes lasting neurodevelopmental and behavioral impairments in neonatal mice.
- Intranasal insulin shows promise as a neuroprotective agent against anesthesia-induced brain damage.
- This study highlights a potential therapeutic strategy to mitigate anesthesia risks in the developing brain.
Abstract:
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.
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