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Purpose <p>Dexmedetomidine is commonly used for its sedative and neuroprotective effects, but its impact on brain activity and sleep architecture is not fully understood. Emerging evidence suggests it may improve postoperative outcomes, particularly in older adults, by promoting sleep-like states with stable hemodynamics, reducing posttraumatic stress, and decreasing delirium. This study aims to better characterize the neurophysiological profile of dexmedetomidine-induced sedation by comparing it to natural sleep in both young and aged mice.</p> Methods <p>Twelve 4–5&#xa0;month old and six 10–18-month-old C57BL/6&#xa0;J male mice were used. Animals were implanted with electroencephalography/electromyography electrodes. After at least 7&#xa0;days of recovery, animals received intraperitoneal injections of saline or dexmedetomidine (50–400&#xa0;µg/kg) and sleep–wake states were recorded for 5–12&#xa0;h.</p> Results <p>Dexmedetomidine significantly increased delta (0.5–4&#xa0;Hz) power beyond levels observed during natural non-rapid eye movement (NREM) sleep, followed by suppression of both high frequency (&gt; 10&#xa0;Hz) electroencephalography activity and REM sleep in a dose dependent manner. Body posture was sprawled during dexmedetomidine versus curled as during natural sleep. Notably, at the transition into sedation, dexmedetomidine induced high-voltage spikes resembling high-voltage spindles and spike wave discharges. These spikes were more prominent in the prefrontal cortex compared to the parietal cortex and aged animals exhibited more high voltage spikes than young adult animals.</p> Conclusion <p>The combination of elevated delta power, high-voltage spikes, suppression of high-frequency activity, and sprawled body posture during dexmedetomidine-induced sedation indicates a state of unconsciousness that is neurophysiologically distinct from natural NREM sleep in mice. These findings highlight important age-related differential responses to dexmedetomidine and help inform its safe and effective use in vulnerable patient populations.</p>

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Neurophysiological differences between dexmedetomidine sedation and natural sleep across the rodent lifespan: implications for aging and perioperative brain health

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月19日

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  • Morgan J. Siegmann,
  • Daniel P. Zachs,
  • Jonathan D. Kenny,
  • Arianna R. S. Lark,
  • Fayaz A. Mir,
  • Eric D. Melonakos,
  • Mohsen Hozan,
  • Sarah Toledano,
  • Rebecca R. Goldblum,
  • Yang Liu,
  • Michael A. Nolan,
  • Gabriella Cohen,
  • Jinyoung Choi,
  • Christian G. White,
  • Eliza A. Crowley,
  • Abigail Hardy Carpenter,
  • Bryton A. Toro,
  • Channing E. Syme,
  • Emery N. Brown,
  • Christa J. Nehs

摘要

Purpose

Dexmedetomidine is commonly used for its sedative and neuroprotective effects, but its impact on brain activity and sleep architecture is not fully understood. Emerging evidence suggests it may improve postoperative outcomes, particularly in older adults, by promoting sleep-like states with stable hemodynamics, reducing posttraumatic stress, and decreasing delirium. This study aims to better characterize the neurophysiological profile of dexmedetomidine-induced sedation by comparing it to natural sleep in both young and aged mice.

Methods

Twelve 4–5 month old and six 10–18-month-old C57BL/6 J male mice were used. Animals were implanted with electroencephalography/electromyography electrodes. After at least 7 days of recovery, animals received intraperitoneal injections of saline or dexmedetomidine (50–400 µg/kg) and sleep–wake states were recorded for 5–12 h.

Results

Dexmedetomidine significantly increased delta (0.5–4 Hz) power beyond levels observed during natural non-rapid eye movement (NREM) sleep, followed by suppression of both high frequency (> 10 Hz) electroencephalography activity and REM sleep in a dose dependent manner. Body posture was sprawled during dexmedetomidine versus curled as during natural sleep. Notably, at the transition into sedation, dexmedetomidine induced high-voltage spikes resembling high-voltage spindles and spike wave discharges. These spikes were more prominent in the prefrontal cortex compared to the parietal cortex and aged animals exhibited more high voltage spikes than young adult animals.

Conclusion

The combination of elevated delta power, high-voltage spikes, suppression of high-frequency activity, and sprawled body posture during dexmedetomidine-induced sedation indicates a state of unconsciousness that is neurophysiologically distinct from natural NREM sleep in mice. These findings highlight important age-related differential responses to dexmedetomidine and help inform its safe and effective use in vulnerable patient populations.