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Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.

Ling-Sha Ju1, Jiepei Zhu1, Jason O Brant2

  • 1Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, Florida.

Anesthesiology
|January 13, 2023
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Summary

Traumatic brain injury combined with anesthesia in male rats can cause long-term neurobehavioral issues and epigenetic changes, affecting their male offspring. This suggests a risk for intergenerational perioperative neurocognitive disorder in males.

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Area of Science:

  • Neuroscience
  • Toxicology
  • Genetics

Background:

  • Traumatic brain injury (TBI), surgery, and sevoflurane anesthesia may interact to cause neurobehavioral problems.
  • This study models intergenerational perioperative neurocognitive disorder in rats.

Purpose of the Study:

  • To test if TBI, surgery, and sevoflurane interact to cause neurobehavioral abnormalities in adult male rats and their offspring.
  • To investigate the underlying molecular and epigenetic mechanisms.

Main Methods:

  • Adult male Sprague-Dawley rats (F0) received TBI with craniectomy and sevoflurane anesthesia.
  • Control, surgery-only, and sevoflurane-only groups were established for comparison.
  • F0 males were mated with control females to produce F1 offspring, whose neurobehavior and hippocampal gene expression were analyzed.

Main Results:

  • F0 injury rats showed acute increases in stress hormones and inflammatory markers, and long-term deficits in behavior and hippocampal gene expression (Nr3c1, BDNF).
  • Male F1 offspring exhibited similar neurobehavioral and epigenetic abnormalities (Nr3c1 promoter hypermethylation), while females were unaffected.
  • These changes were linked to elevated corticosterone, interleukin-1β, and -6 levels.

Conclusions:

  • Young adult male rats experiencing TBI and anesthesia are at risk for developing perioperative neurocognitive disorder.
  • This risk extends to their male offspring, indicating an intergenerational effect.
  • Epigenetic modifications, specifically Nr3c1 promoter hypermethylation, may mediate these transgenerational effects.