Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice
Blood–brain barrier (BBB) dysfunction, e.g., increase in BBB permeability, has been reported to contribute to cognitive impairment. However, the effects of anesthesia and surgery on BBB permeability, the underlying mechanisms, and associated cognitive function remain largely to be determined. Here,...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2017-08-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00902/full |
id |
doaj-16e8ee04924b450ead591b447b7faa10 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siming Yang Siming Yang Changping Gu Changping Gu Emiri T. Mandeville Yuanlin Dong Elga Esposito Yiying Zhang Guang Yang Yuan Shen Xiaobing Fu Eng H. Lo Zhongcong Xie |
spellingShingle |
Siming Yang Siming Yang Changping Gu Changping Gu Emiri T. Mandeville Yuanlin Dong Elga Esposito Yiying Zhang Guang Yang Yuan Shen Xiaobing Fu Eng H. Lo Zhongcong Xie Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice Frontiers in Immunology anesthesia/surgery interleukin-6 blood–brain barrier age cognition |
author_facet |
Siming Yang Siming Yang Changping Gu Changping Gu Emiri T. Mandeville Yuanlin Dong Elga Esposito Yiying Zhang Guang Yang Yuan Shen Xiaobing Fu Eng H. Lo Zhongcong Xie |
author_sort |
Siming Yang |
title |
Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice |
title_short |
Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice |
title_full |
Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice |
title_fullStr |
Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice |
title_full_unstemmed |
Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice |
title_sort |
anesthesia and surgery impair blood–brain barrier and cognitive function in mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-08-01 |
description |
Blood–brain barrier (BBB) dysfunction, e.g., increase in BBB permeability, has been reported to contribute to cognitive impairment. However, the effects of anesthesia and surgery on BBB permeability, the underlying mechanisms, and associated cognitive function remain largely to be determined. Here, we assessed the effects of surgery (laparotomy) under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h on BBB permeability, levels of junction proteins and cognitive function in both 9- and 18-month-old wild-type mice and 9-month-old interleukin (IL)-6 knockout mice. BBB permeability was determined by dextran tracer (immunohistochemistry imaging and spectrophotometric quantification), and protein levels were measured by Western blot and cognitive function was assessed by using both Morris water maze and Barnes maze. We found that the anesthesia/surgery increased mouse BBB permeability to 10-kDa dextran, but not to 70-kDa dextran, in an IL-6-dependent and age-associated manner. In addition, the anesthesia/surgery induced an age-associated increase in blood IL-6 level. Cognitive impairment was detected in 18-month-old, but not 9-month-old, mice after the anesthesia/surgery. Finally, the anesthesia/surgery decreased the levels of β-catenin and tight junction protein claudin, occludin and ZO-1, but not adherent junction protein VE-cadherin, E-cadherin, and p120-catenin. These data demonstrate that we have established a system to study the effects of perioperative factors, including anesthesia and surgery, on BBB and cognitive function. The results suggest that the anesthesia/surgery might induce an age-associated BBB dysfunction and cognitive impairment in mice. These findings would promote mechanistic studies of postoperative cognitive impairment, including postoperative delirium. |
topic |
anesthesia/surgery interleukin-6 blood–brain barrier age cognition |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00902/full |
work_keys_str_mv |
AT simingyang anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT simingyang anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT changpinggu anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT changpinggu anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT emiritmandeville anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT yuanlindong anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT elgaesposito anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT yiyingzhang anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT guangyang anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT yuanshen anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT xiaobingfu anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT enghlo anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice AT zhongcongxie anesthesiaandsurgeryimpairbloodbrainbarrierandcognitivefunctioninmice |
_version_ |
1725644969965780992 |
spelling |
doaj-16e8ee04924b450ead591b447b7faa102020-11-24T22:59:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00902287753Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in MiceSiming Yang0Siming Yang1Changping Gu2Changping Gu3Emiri T. Mandeville4Yuanlin Dong5Elga Esposito6Yiying Zhang7Guang Yang8Yuan Shen9Xiaobing Fu10Eng H. Lo11Zhongcong Xie12Key Laboratory of Wound Repair and Regeneration of PLA, College of Life Sciences, General Hospital of PLA, Medical College of PLA, Beijing, ChinaGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesDepartment of Anesthesiology, Shandong Provincial Qianfoshan Hospital, Jinan, ChinaNeuroprotection Research, Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesNeuroprotection Research, Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesDepartment of Anesthesiology, Perioperative Care and Pain Medicine, New York University School of Medicine, New York, NY, United StatesDepartment of Psychiatry, Tenth People’s Hospital of Tongji University, Shanghai, ChinaKey Laboratory of Wound Repair and Regeneration of PLA, College of Life Sciences, General Hospital of PLA, Medical College of PLA, Beijing, ChinaNeuroprotection Research, Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesGeriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United StatesBlood–brain barrier (BBB) dysfunction, e.g., increase in BBB permeability, has been reported to contribute to cognitive impairment. However, the effects of anesthesia and surgery on BBB permeability, the underlying mechanisms, and associated cognitive function remain largely to be determined. Here, we assessed the effects of surgery (laparotomy) under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h on BBB permeability, levels of junction proteins and cognitive function in both 9- and 18-month-old wild-type mice and 9-month-old interleukin (IL)-6 knockout mice. BBB permeability was determined by dextran tracer (immunohistochemistry imaging and spectrophotometric quantification), and protein levels were measured by Western blot and cognitive function was assessed by using both Morris water maze and Barnes maze. We found that the anesthesia/surgery increased mouse BBB permeability to 10-kDa dextran, but not to 70-kDa dextran, in an IL-6-dependent and age-associated manner. In addition, the anesthesia/surgery induced an age-associated increase in blood IL-6 level. Cognitive impairment was detected in 18-month-old, but not 9-month-old, mice after the anesthesia/surgery. Finally, the anesthesia/surgery decreased the levels of β-catenin and tight junction protein claudin, occludin and ZO-1, but not adherent junction protein VE-cadherin, E-cadherin, and p120-catenin. These data demonstrate that we have established a system to study the effects of perioperative factors, including anesthesia and surgery, on BBB and cognitive function. The results suggest that the anesthesia/surgery might induce an age-associated BBB dysfunction and cognitive impairment in mice. These findings would promote mechanistic studies of postoperative cognitive impairment, including postoperative delirium.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00902/fullanesthesia/surgeryinterleukin-6blood–brain barrieragecognition |