Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.
BACKGROUND
Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies.


METHODS
In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6.


RESULTS
On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test.


CONCLUSIONS
Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
Xiaomei
X
Feng
Vincent
V
Degos
Lauren G
LG
Koch
Steven L
SL
Britton
Yinggang
Y
Zhu
Susana
S
Vacas
Niccolò
N
Terrando
Jeffrey
J
Nelson
Xiao
X
Su
Mervyn
M
Maze
D000704:Analysis of Variance; D000768:Anesthesia, General; D000818:Animals; D003072:Cognition Disorders / Q000150:complications / Q000523:psychology*; D003213:Conditioning, Psychological; D003463:Cues; D005239:Fear / Q000523:psychology; D007109:Immunity / Q000502:physiology; D007249:Inflammation / Q000473:pathology; D008297:Male; D018782:Maze Learning; D057567:Memory, Long-Term / Q000502:physiology; D024821:Metabolic Syndrome / Q000150:complications / Q000523:psychology*; D009043:Motor Activity / Q000502:physiology; D011183:Postoperative Complications / Q000209:etiology / Q000523:psychology*; D051381:Rats; D012420:Running / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D013550:Swimming / Q000523:psychology; D013978:Tibial Fractures / Q000523:psychology / Q000601:surgery