Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension.
BACKGROUND
Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia.


METHODS
Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia.


RESULTS
Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension.


CONCLUSIONS
In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.
Li
Min
M
Department of Anesthesiology and Critical Care, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Bertout
Jessica A
JA
Ratcliffe
Sarah J
SJ
Eckenhoff
Maryellen F
MF
Simon
M Celeste
MC
Floyd
Thomas F
TF
D000208:Acute Disease; D000375:Aging / Q000523:psychology*; D000740:Anemia / Q000150:complications* / Q000523:psychology*; D000758:Anesthesia; D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D015687:Cell Hypoxia; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology* / Q000523:psychology*; D006438:Hemodilution; D006973:Hypertension / Q000150:complications* / Q000523:psychology*; D002534:Hypoxia, Brain / Q000209:etiology* / Q000523:psychology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers
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