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Spatial and temporal alterations of developing oligodendrocytes induced by repeated sevoflurane exposure in neonatal mice. | LitMetric

AI Article Synopsis

  • - The study investigates how repeated exposure to sevoflurane, a type of general anesthesia, affects oligodendrocytes (cells that support and insulate nerve cells) and cognitive functions like executive function and motor skills in developing brains.
  • - Researchers found that while the overall number of oligodendrocytes remained stable after anesthesia exposure, there were significant structural issues and a reduction in mature oligodendrocytes, particularly in regions of the brain linked to learning and memory.
  • - Treatment with clemastine, which promotes the development of oligodendrocytes and myelin, improved cognitive performance, suggesting potential therapeutic approaches to address cognitive impairments associated with early anesthetic exposure.

Article Abstract

The general anesthesia associated with long-term cognitive impairment has been causing the concern of the whole society. In particular, repeated anesthetic exposures may affect executive function, processing speed, and fine motor skills, which all directly depended on the functions of oligodendrocytes, myelin, and axons. However, the underlying mechanisms are still largely unknown. To investigate the spatial and temporal alterations in oligodendrocytes in the corpus callosum (CC) and hippocampus following repeated sevoflurane exposures (3%, for 2 h) from postnatal day 6 (P6) to P8, we used immunofluorescence, Western blot, and a battery of behavioral tests. As previously stated, we confirmed that early anesthetic exposures hampered both cognitive and motor performance during puberty in the rotarod and banes tests. Intriguingly, we discovered that the proliferation of oligodendrocyte progenitor cells (OPCs) was immediately enhanced after general anesthesia in the CC and hippocampus from P8 to P32. From P8 through P15, the overall oligodendrocyte population remained constant. However, along with the structural myelin abnormalities, the matured oligodendrocytes statistically reduced in the CC (from P15) and hippocampus (from P32). Administration of clemastine, which could induce OPC differentiation and myelin formation, significantly increased matured oligodendrocytes and promoted myelination and cognition. Collectively, we first demonstrated the bi-directional influence of early sevoflurane exposures on oligodendrocyte maturation and proliferation, which contributes to the cognitive impairment induced by general anesthesia. These findings illustrated the dynamic changes in oligodendrocytes in the developing brain following anesthetic exposures, as well as possible therapeutic strategies for multiple general anesthesia associated cognitive impairment.

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Source
http://dx.doi.org/10.1016/j.bbrc.2022.11.105DOI Listing

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