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. 2008 Sep;43(9):840-6.
doi: 10.1016/j.exger.2008.06.004. Epub 2008 Jun 19.

Neuroinflammation and cognitive function in aged mice following minor surgery

Affiliations

Neuroinflammation and cognitive function in aged mice following minor surgery

H A Rosczyk et al. Exp Gerontol. 2008 Sep.

Abstract

Following surgery, elderly patients often suffer from postoperative cognitive dysfunction (POCD) which can persist long after physical recovery. It is known that surgery-induced tissue damage activates the peripheral innate immune system resulting in the release of inflammatory mediators. Compared to adults, aged animals demonstrate increased neuroinflammation and microglial priming that leads to an exaggerated proinflammatory cytokine response following activation of the peripheral immune system. Therefore, we sought to determine if the immune response to surgical trauma results in increased neuroinflammation and cognitive impairment in aged mice. Adult and aged mice underwent minor abdominal surgery and 24h later hippocampal cytokines were measured and working memory was assessed in a reversal learning version of the Morris water maze. While adult mice showed no signs of neuroinflammation following surgery, aged mice had significantly increased levels of IL-1beta mRNA in the hippocampus. Minor surgery did not result in severe cognitive impairment although aged mice that underwent surgery did tend to perseverate in the old target during reversal testing suggesting reduced cognitive flexibility. Overall these results suggest that minor surgery leads to an exaggerated neuroinflammatory response in aged mice but does not result in significantly impaired performance in the Morris water maze.

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Figures

Fig. 1
Fig. 1
Surgery increases IL-1β mRNA levels in the hippocampus of aged mice. IL-1β (A), IL-6 (B), and TNF-α (C) mRNA levels were measured in the hippocampus of adult and aged mice 24 h following surgery. Bars represent means ±S.E.M. Means with different letters (a, b, or c) are significantly different (p <0.05) from each other.
Fig. 2
Fig. 2
Locomotor activity is not depressed in adult or aged mice following surgery. Locomotor behavior (lines crossed) was measured both immediately before (0 h) and 24 h after surgery in adult and aged mice. Bars represent means ±S.E.M. Means with different letters (a or b) are significantly different (p <0.05) from each other.
Fig. 3
Fig. 3
Performance of adult and aged mice during a 6 day acquisition phase in the Morris water maze. (A) Distance swam to platform across testing days. (B) Latency to find the platform across testing days. (C) Swim speed across testing days. Data are represented as means ±S.E.M. Means with * are significantly different (p <0.05).
Fig. 4
Fig. 4
Surgery does not impair basic performance parameters in the Morris water maze. After 6-days of acquisition training, mice were evaluated in a reversal test 24 h after surgery. (A) Distance swam to platform during reversal testing. (B) Latency to find the platform during reversal testing. (C) Swim speed during reversal testing. Bars represent means ±S.E.M. Means with different letters (a or b) are significantly different (p <0.05) from each other.
Fig. 5
Fig. 5
Effects of surgery on performance of adult and aged mice during reversal testing in the Morris water maze. (A) Aged mice that underwent surgery spent significantly more time perseverating in the old target quadrant than adult mice that underwent the same procedure. (B) In addition, aged surgical mice spent significantly less time in the new target quadrant compared to their age-matched controls. Data are represented as means ±S.E.M. Means with * are significantly different (p <0.05).

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