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October 13, 2012
8:00:00 AM - 9:30:00 AM
Room 103B
Forced Wakefulness Enhances Neuroinflammation in Postoperative Mice
Susana Vacas, M.D., Vincent Degos, M.D.,Ph.D., Mervyn Maze, M.B.,Ch.B.
University of California San Francisco, San Francisco, California, United States

Sleep restores and repairs several mechanisms related to learning and memory. Within the brain, the slow wave activity, weakens the synaptic strengthening that occurs during wakefulness1 and restores the brain to a state that is subsequently capable of appropriately processing sensory input in the succeeding period of wakefulness2. Surgery (Sx) activates the innate immune system, inducing neuroinflammatory changes that interferes with cognition3. Sleep disruption, as occurs frequently in surgical patients, impairs learning and memory as well as the immune system4,5. Here we have investigated the contribution of wakefulness, either pre- or post-operatively, to the neuroinflammatory and cognitive responses to Sx.


C57BL/6J wild-type mice underwent stabilized tibial fracture operation (under analgesia and general anesthesia) and were sleep deprived for 24h (either pre or post operatively). Separate cohorts of mice were tested for either memory, using the trace-fear conditioning paradigm, or hippocampal inflammation, using transcription of pro-inflammatory cytokines.


Sleep deprivation (SD) and Sx caused hippocampal-dependent memory impairment (p<0.05) (fig.1). One day after either SD or Sx there was a significant increase in IL6, and TNF-alpha mRNA. These increments were more pronounced when either pre or post operative SD was combined with Sx. Memory impairment was not exacerbated by combining SD with Sx (fig. 1).


Sleep deprivation and surgery alone induce significant changes that underlie memory impairment. While perioperative sleep deprivation induced significant neuroinflammatory changes, these did not translate into worse memory impairment. The dissociation between neuroinflammation and cognitive decline may relate to our use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.


1.Tononi, G et al, Sleep Med Rev 10, 49-62 (2006)

2.Fenn, KM,et al, Nature 425, 614-616 (2003)

3.Cibelli, M, et a, Ann Neurol 68, 360-368 (2010)

4.Majde, JA et al,J Allergy Clin Immunol 116, 1188-1198 (2005).

5.Mullington, JM et al, Prog Cardiovasc Dis 51, 294-302 (2009).

Supported in part by a grant from the Programme for Advanced Medical Education, Portugal (to Dr. Vacas).

Figure 1

Copyright © 2012 American Society of Anesthesiologists