Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus

Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.


Background: Postoperative cognitive dysfunction is being increasingly reported as a complication. The authors investigated the role of cytokine-mediated inflammation within the central nervous system in the development of cognitive dysfunction in a rat model.

Methods: Adult rats were subjected to neuroleptic anesthesia (20 microg/kg fentanyl plus 500 microg/kg droperidol, intraperitoneal) for splenectomy or no surgery. On postanesthetic days 1, 3, and 7, cognitive function was assessed in a Y maze. To evaluate the immune response in the hippocampus, the authors measured glial activation, as well as transcription and expression of key proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. To determine propensity for apoptosis, they measured expression of Bax and Bcl-2.

Results: Cognitive function in splenectomized animals was impaired at days 1 and 3 after surgery compared with cognitive function in nonanesthetized rats. At all times, anesthetized rats that were not subjected to surgery were no different from control rats. Glial activation was observed in the hippocampus only in splenectomized rats at postsurgery days 1 and 3. Interleukin-1beta messenger RNA (mRNA) was significantly increased at postsurgery days 1 and 3, with an increase in protein expression detected on day 1. There was a significant increase in tumor necrosis factor-alpha mRNA on day 1 after surgery, although this was not associated with an increase in protein expression. The ratio of Bcl-2:Bax was significantly decreased in the splenectomized animals.

Conclusion: These results suggest that splenectomy performed during neuroleptic anesthesia triggers a cognitive decline that is associated with a hippocampal inflammatory response that seems to be due to proinflammatory cytokine-dependent activation of glial cells.

MeSH terms

  • Adjuvants, Anesthesia / adverse effects
  • Analgesics, Opioid / adverse effects
  • Animals
  • Cognition Disorders / etiology*
  • Cognition Disorders / immunology
  • Cytokines / immunology*
  • Disease Models, Animal
  • Droperidol / adverse effects
  • Fentanyl / adverse effects
  • Hippocampus / drug effects*
  • Hippocampus / immunology
  • Inflammation / etiology*
  • Inflammation / immunology
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / immunology
  • Male
  • Maze Learning / drug effects
  • Neuroglia / drug effects
  • Neuroglia / immunology
  • Neuroleptanalgesia / adverse effects*
  • Polymerase Chain Reaction / methods
  • Postoperative Complications / etiology*
  • Postoperative Complications / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Splenectomy / adverse effects*
  • Time Factors
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / immunology


  • Adjuvants, Anesthesia
  • Analgesics, Opioid
  • Cytokines
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Droperidol
  • Fentanyl