Cerebral cortical gene expression in acutely anemic rats: a microarray analysis.
OBJECTIVE
Hemodilution in perioperative patients has been associated with neurological morbidity and increased mortality by undefined mechanisms. This study assesses whether hemodilutional anemia up-regulated inflammatory cerebral gene expression (microarray) to help define the mechanism.


METHODS
Hemodilution was performed in anesthetized rats by exchanging 50% of the estimated blood volume (30 mL kg(-1)) with pentastarch. Two groups of control animals were utilized, i.e., a non-anesthetized control (Normal Control) and an anesthetized control group (Anesthesia Control). Blood pressure, hemoglobin concentration, and arterial blood gas analysis were performed before and after hemodilution. Cerebral cortex was harvested from isoflurane-anesthetized rats (n = 6) after 6 and 24 hr of recovery and was used to perform complimentary DNA (cDNA) microarray analyses. Pro-inflammatory chemokine and cytokine protein levels were also measured.


RESULTS
Microarray analysis demonstrated up-regulation of 72 and 27 genes (6 and 24 hr, respectively) in anemic cerebral cortex. These genes were involved in a number of biological functions, including (1) inflammatory responses; (2) angiogenesis; (3) vascular homeostasis; (4) cellular biology; and (5) apoptosis. Chemokine ribonucleic acid (RNA) expression (CXCL-1, -10, and -11) was highest in anemic brain tissue (P < 0.0125 for each). Protein measurements demonstrated a significant increase in interleukin-6, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 (P < 0.05 for each).


CONCLUSIONS
This study utilizes microarray technology to elucidate changes in cerebral cortical gene expression in response to acute hemodilution. These findings demonstrate an increase in pro-inflammatory chemokines (RNA, protein) and cytokines (protein). An improved understanding of the inflammatory response to anemia may help to minimize associated morbidity and mortality.
Department of Anaesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Françoise
F
Briet
C David
CD
Mazer
Albert K Y
AK
Tsui
Haibo
H
Zhang
Julie
J
Khang
Victoria
V
Pang
Andrew J
AJ
Baker
Gregory M T
GM
Hare
D000740:Anemia / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D006438:Hemodilution / Q000009:adverse effects*; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D018925:Chemokines; D016207:Cytokines; D006895:Hydroxyethyl Starch Derivatives