TY - JOUR
T1 - Postoperative cognitive dysfunction
T2 - Involvement of neuroinflammation and neuronal functioning
AU - Hovens, Iris B.
AU - Schoemaker, Regien G.
AU - van der Zee, Eddy A.
AU - Absalom, Anthony R.
AU - Heineman, Erik
AU - van Leeuwen, Barbara L.
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/5
Y1 - 2014/5
N2 - Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3 months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation. BDNF and neurogenesis were assessed at 1, 2 and 3 weeks following surgery.Rats displayed changes in exploratory activity shortly after surgery, associated with postoperatively elevated IL-6 plasma levels. Spatial learning and memory were temporarily impaired in the first 2 weeks following surgery, whereas non-spatial cognitive functions seemed unaffected. Analysis of brain tissue revealed increased neuroinflammation (IL-1B and microgliosis) 7 days following surgery, decreased BDNF levels on postoperative day 14 and 21, and decreased neurogenesis until at least 21 days following surgery.These findings indicate that in young adult rats only spatial learning and memory is affected by surgery, suggesting hippocampal dependent cognition is especially vulnerable to surgery-induced impairment. The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact. (C) 2014 Elsevier Inc. All rights reserved.
AB - Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3 months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation. BDNF and neurogenesis were assessed at 1, 2 and 3 weeks following surgery.Rats displayed changes in exploratory activity shortly after surgery, associated with postoperatively elevated IL-6 plasma levels. Spatial learning and memory were temporarily impaired in the first 2 weeks following surgery, whereas non-spatial cognitive functions seemed unaffected. Analysis of brain tissue revealed increased neuroinflammation (IL-1B and microgliosis) 7 days following surgery, decreased BDNF levels on postoperative day 14 and 21, and decreased neurogenesis until at least 21 days following surgery.These findings indicate that in young adult rats only spatial learning and memory is affected by surgery, suggesting hippocampal dependent cognition is especially vulnerable to surgery-induced impairment. The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact. (C) 2014 Elsevier Inc. All rights reserved.
KW - Postoperative cognitive dysfunction
KW - Surgery
KW - Learning and memory
KW - Exploratory behavior
KW - Neuroinflammation
KW - Brain-derived neurotrophic factor
KW - Neurogenesis
KW - ANTIINFLAMMATORY RESPONSE SYNDROME
KW - HIPPOCAMPAL MEMORY CONSOLIDATION
KW - C-REACTIVE PROTEIN
KW - MORRIS WATER MAZE
KW - INFLAMMATORY RESPONSE
KW - NEUROTROPHIC FACTOR
KW - NONCARDIAC SURGERY
KW - OBJECT RECOGNITION
KW - BEHAVIORAL-CHANGES
KW - IMMUNE-RESPONSE
U2 - 10.1016/j.bbi.2014.02.002
DO - 10.1016/j.bbi.2014.02.002
M3 - Article
C2 - 24517920
SN - 0889-1591
VL - 38
SP - 202
EP - 210
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -