Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain.
BACKGROUND
Exposure of rhesus macaque fetuses for 24 h or neonates for 9 h to ketamine anesthesia causes neuroapoptosis in the developing brain. The current study clarifies the minimum exposure required for and the extent and spatial distribution of ketamine-induced neuroapoptosis in rhesus fetuses and neonates.


METHODS
Ketamine was administered by IV infusion for 5 h to postnatal day 6 rhesus neonates or to pregnant rhesus females at 120 days' gestation (full term = 165 days). Three hours later, fetuses were delivered by cesarean section, and the fetal and neonatal brains were studied for evidence of apoptotic neurodegeneration, as determined by activated caspase-3 staining.


RESULTS
Both the fetal (n = 3) and neonatal (n = 4) ketamine-exposed brains had a significant increase in apoptotic profiles compared with drug-naive controls (fetal n = 4; neonatal n = 5). Loss of neurons attributable to ketamine exposure was 2.2 times greater in fetuses than in neonates. The pattern of neurodegeneration in fetuses was different from that in neonates, and all subjects exposed at either age had a pattern characteristic for that age.


CONCLUSIONS
The developing rhesus macaque brain is sensitive to the apoptogenic action of ketamine at both a fetal and neonatal age, and exposure duration of 5 h is sufficient to induce a significant neuroapoptosis response at either age. The pattern of neurodegeneration induced by ketamine in fetuses was different from that in neonates, and loss of neurons attributable to ketamine exposure was 2.2 times greater in the fetal than neonatal brains.
Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, Oregon 97239-3098, USA. brambrin@ohsu.edu
Ansgar M
AM
Brambrink
Alex S
AS
Evers
Michael S
MS
Avidan
Nuri B
NB
Farber
Derek J
DJ
Smith
Lauren D
LD
Martin
Gregory A
GA
Dissen
Catherine E
CE
Creeley
John W
JW
Olney
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D008253:Macaca mulatta; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D011247:Pregnancy; D011897:Random Allocation
D007649:Ketamine