Open AccessSurgery Upregulates High Mobility Group Box‐1 and Disrupts the Blood–Brain Barrier causing Cognitive Dysfunction in Aged Rats
Author(s) -
He HuiJuan,
Wang Yi,
Le Yuan,
Duan KaiMing,
Yan XueBin,
Liao Qin,
Liao Yan,
Tong JianBin,
Terrando Niccolò,
Ouyang Wen
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12018
Subject(s) - postoperative cognitive dysfunction , morris water navigation task , medicine , proinflammatory cytokine , blood–brain barrier , rage (emotion) , hippocampus , anesthesia , isoflurane , inflammation , glycation , cognition , psychology , receptor , central nervous system , neuroscience , psychiatry
Summary Aim Postoperative cognitive dysfunction ( POCD ) is a growing and largely underestimated problem without defined etiology. Herein, we sought to determine the relationship between cognitive decline, blood–brain barrier ( BBB ) permeability, and inflammation, namely high mobility group box‐1 ( HMGB 1), after surgery in aged rats. Methods Aged rats were randomly assigned as surgery group (n = 45, splenectomy under general anesthesia), anesthesia (n = 45, 2% isoflurane for 2 h), and naïve control (n = 15). Markers of inflammation were measured in plasma and brain. Blood–brain barrier ultrastructure and permeability were measured by transmission electron microscope ( TEM ) and I g G immunohistochemistry. Cognitive function was assessed in a reversal learning version of the Morris water maze ( MWM ). Results Surgical trauma under general anesthesia caused distinct changes in systemic and central proinflammatory cytokines. Levels of HMGB 1 and the receptor for advanced glycation end products ( RAGE ) were significantly upregulated in the hippocampus of operated animals. Immunohistochemistry and TEM showed BBB disruption induced by surgery and anesthesia. These molecular changes were associated with cognitive impairment in latency with the MWM up to postoperative day 3. Conclusions HMGB 1 and RAGE signaling appear pivotal mediators of surgery‐induced cognitive decline and may contribute to the changes in BBB permeability after peripheral surgical trauma.