Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats.
BACKGROUND
Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats. We tested the hypothesis that isoflurane impairs neurogenesis and hippocampal function in aged rats.


METHODS
Isoflurane was administered to 16-month-old rats at one minimum alveolar concentration for 4 h. FluoroJade staining was performed to assess brain cell death 16 h after isoflurane administration. Dentate gyrus progenitor proliferation was assessed by bromodeoxyuridine injection 4 days after anesthesia and quantification of bromodeoxyuridine+ cells 12 h later. Neuronal differentiation was studied by determining colocalization of bromodeoxyuridine with the immature neuronal marker NeuroD 5 days after anesthesia. New neuronal survival was assessed by quantifying cells coexpressing bromodeoxyuridine and the mature neuronal marker NeuN 5 weeks after anesthesia. Four months after anesthesia, associative learning was assessed by fear conditioning. Spatial reference memory acquisition and retention was tested in the Morris Water Maze.


RESULTS
Cell death was sporadic and not different between groups. We did not detect any differences in hippocampal progenitor proliferation, neuronal differentiation, new neuronal survival, or in any of the tests of long-term hippocampal function.


CONCLUSIONS
In aged rats, isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome.
Stratmann
Greg
G
Department of Anesthesia, University of California-San Francisco, 513 Parnassus Ave., San Francisco, California 94143, USA. stratman@anesthesia.ucsf.edu
Sall
Jeffrey W
JW
Bell
Joseph S
JS
Alvi
Rehan S
RS
May
Laura d V
Ld
Ku
Ban
B
Dowlatshahi
Mitra
M
Dai
Ran
R
Bickler
Philip E
PE
Russell
Isobel
I
Lee
Michael T
MT
Hrubos
Margit W
MW
Chiu
Cheryl
C
D000375:Aging / Q000502:physiology / Q000523:psychology; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000523:psychology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D007150:Immunohistochemistry; D007530:Isoflurane / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D016896:Treatment Outcome
D018685:Anesthetics, Inhalation; D007530:Isoflurane