Editors' ChoiceAnesthesiology

Shocking Memories After Surgery

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Science Translational Medicine  13 Apr 2011:
Vol. 3, Issue 78, pp. 78ec51
DOI: 10.1126/scitranslmed.3002482

Amnesia is a good thing during general anesthesia and occurs at low anesthetic concentrations. However, when memory is impaired beyond the events of an operation, it becomes a disorder in its own right. Postoperative cognitive dysfunction, defined as impairment of mental capacities that persists for at least three months after surgery, is a serious health problem. Developing useful animal models and elucidating underlying mechanisms of this serious complication of surgery are key goals for the field; the current work by Vizcaychipi and colleagues contributes to both of these aims by introducing a mouse model in which they show that up-regulation of a heat shock protein can protect against postoperative memory impairment.

The investigators describe a new mouse model of orthopedic surgery under general anesthesia; they trained the mice beforehand on a fear-conditioning task and tested their memory of the learned task afterward. The authors found that surgery under isoflurane anesthesia, as well as anesthesia alone, resulted in impairment of postoperative memory, both for tasks that required the hippocampus and for those that did not. What did they learn about the mechanism? To test whether a protective cellular function could prevent the memory deficit, Vizcaychipi and colleagues compared the effects of anesthesia in wild-type mice with those in a transgenic line overexpressing heat shock protein 72 (Hsp72), a protein induced during stress that performs numerous cell-protective functions and plays a role in learning and memory. Brain levels of Hsp72 were approximately 10 times higher than normal in this transgenic strain; remarkably, the mice overexpressing Hsp72 showed no evidence of memory impairment after surgery or after anesthesia alone. The authors were unable to correlate these findings with reduced numbers of activated microglia (the brain’s immune cells) in the hippocampus, suggesting that there is an alternative mechanism.

Vizcaychipi et al. present an animal model for postoperative cognitive dysfunction that is sensitive to the effects of both anesthesia and surgery. Their results implicate stress responses in the brain as modifiers of this memory impairment. Further translational research is needed to clarify mechanisms of impairment and to identify therapeutic targets.

M. P. Vizcaychipi et al., Heat shock protein 72 overexpression prevents early postoperative memory decline after orthopedic surgery under general anesthesia in mice. Anesthesiology 114, 891–900 (2011). [Abstract]

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