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Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline.

Publication ,  Journal Article
Terrando, N; Gómez-Galán, M; Yang, T; Carlström, M; Gustavsson, D; Harding, RE; Lindskog, M; Eriksson, LI
Published in: FASEB J
September 2013

Hospitalization for major surgery or critical illness often associates with cognitive decline. Inflammation and dysregulation of the innate immune system can exert broad effects in the periphery and central nervous system (CNS), yet the mechanisms underlying memory impairment after surgery remain poorly understood and without effective therapy. Endogenous regulation of acute inflammation is providing novel approaches to treat several disease states including sepsis, pain, obesity and diabetes. Resolvins are potent endogenous lipid mediators biosynthesized during the resolution phase of acute inflammation that display immunoresolvent actions. Here, using a mouse model of surgery-induced cognitive decline we report that orthopedic surgery affects hippocampal neuronal-glial function, including synaptic transmission and plasticity. Systemic prophylaxis with aspirin-triggered resolvin D1 (AT-RvD1: 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, as little as 100 ng dose per mouse) improved memory decline following surgery and abolished signs of synaptic dysfunction. Moreover, delayed administration 24 h after surgery also attenuated signs of neuronal dysfunction postoperatively. AT-RvD1 also limited peripheral damage by modulating the release of systemic interleukin (IL)-6 and improved other clinical markers of tissue injury. Collectively, these results demonstrate a novel role of AT-RvD1 in modulating the proinflammatory milieu after aseptic injury and protecting the brain from neuroinflammation, synaptic dysfunction and cognitive decline. These findings provide novel and safer approaches to treat postoperative cognitive decline and potentially other forms of memory dysfunctions.

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

September 2013

Volume

27

Issue

9

Start / End Page

3564 / 3571

Location

United States

Related Subject Headings

  • Superoxides
  • Postoperative Complications
  • Mice
  • Male
  • Macrophages, Peritoneal
  • Long-Term Potentiation
  • Locomotion
  • In Vitro Techniques
  • Immunohistochemistry
  • Electrophysiology
 

Citation

APA
Chicago
ICMJE
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Terrando, N., Gómez-Galán, M., Yang, T., Carlström, M., Gustavsson, D., Harding, R. E., … Eriksson, L. I. (2013). Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. FASEB J, 27(9), 3564–3571. https://doi.org/10.1096/fj.13-230276
Terrando, Niccolò, Marta Gómez-Galán, Ting Yang, Mattias Carlström, Daniel Gustavsson, Ralph E. Harding, Maria Lindskog, and Lars I. Eriksson. “Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline.FASEB J 27, no. 9 (September 2013): 3564–71. https://doi.org/10.1096/fj.13-230276.
Terrando N, Gómez-Galán M, Yang T, Carlström M, Gustavsson D, Harding RE, et al. Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. FASEB J. 2013 Sep;27(9):3564–71.
Terrando, Niccolò, et al. “Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline.FASEB J, vol. 27, no. 9, Sept. 2013, pp. 3564–71. Pubmed, doi:10.1096/fj.13-230276.
Terrando N, Gómez-Galán M, Yang T, Carlström M, Gustavsson D, Harding RE, Lindskog M, Eriksson LI. Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline. FASEB J. 2013 Sep;27(9):3564–3571.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

September 2013

Volume

27

Issue

9

Start / End Page

3564 / 3571

Location

United States

Related Subject Headings

  • Superoxides
  • Postoperative Complications
  • Mice
  • Male
  • Macrophages, Peritoneal
  • Long-Term Potentiation
  • Locomotion
  • In Vitro Techniques
  • Immunohistochemistry
  • Electrophysiology