Perioperative Medicine  |   December 2016
Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity
Author Notes
  • From the Department of Anesthesia, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China (Y.J., Q.L.); Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China, (D.T.); Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (Y.J., D.T., R.D.H., A.W.L., S.C.D.); and Departments of Anesthesia and Pediatrics (A.W.L., S.C.D.) and Neuroscience Graduate Program (R.D.H., A.W.L., S.C.D.), University of Cincinnati, Cincinnati, Ohio.
  • Submitted for publication October 5, 2016. Accepted for publication August 2, 2016.
    Submitted for publication October 5, 2016. Accepted for publication August 2, 2016.×
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • Corresponding article on page 1090.
    Corresponding article on page 1090.×
  • Address correspondence to Dr. Danzer: Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, ML 2001, Cincinnati, Ohio 45229. steve.danzer@cchmc.org. Dr. Lian can be reached at lianqingquanmz@163.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   December 2016
Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity
Anesthesiology 12 2016, Vol.125, 1159-1170. doi:10.1097/ALN.0000000000001358
Anesthesiology 12 2016, Vol.125, 1159-1170. doi:10.1097/ALN.0000000000001358
Abstract

Background: Exposure to isoflurane increases apoptosis among postnatally generated hippocampal dentate granule cells. These neurons play important roles in cognition and behavior, so their permanent loss could explain deficits after surgical procedures.

Methods: To determine whether developmental anesthesia exposure leads to persistent deficits in granule cell numbers, a genetic fate-mapping approach to label a cohort of postnatally generated granule cells in Gli1-CreERT2::GFP bitransgenic mice was utilized. Green fluorescent protein (GFP) expression was induced on postnatal day 7 (P7) to fate map progenitor cells, and mice were exposed to 6 h of 1.5% isoflurane or room air 2 weeks later (P21). Brain structure was assessed immediately after anesthesia exposure (n = 7 controls and 8 anesthesia-treated mice) or after a 60-day recovery (n = 8 controls and 8 anesthesia-treated mice). A final group of C57BL/6 mice was exposed to isoflurane at P21 and examined using neurogenesis and cell death markers after a 14-day recovery (n = 10 controls and 16 anesthesia-treated mice).

Results: Isoflurane significantly increased apoptosis immediately after exposure, leading to cell death among 11% of GFP-labeled cells. Sixty days after isoflurane exposure, the number of GFP-expressing granule cells in treated animals was indistinguishable from control animals. Rates of neurogenesis were equivalent among groups at both 2 weeks and 2 months after treatment.

Conclusions: These findings suggest that the dentate gyrus can restore normal neuron numbers after a single, developmental exposure to isoflurane. The authors’ results do not preclude the possibility that the affected population may exhibit more subtle structural or functional deficits. Nonetheless, the dentate appears to exhibit greater resiliency relative to nonneurogenic brain regions, which exhibit permanent neuron loss after isoflurane exposure.