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Anesthesiology. 2014 Nov;121(5):1010-7. doi: 10.1097/ALN.0000000000000366.

Endocrine and neurobehavioral abnormalities induced by propofol administered to neonatal rats.

Author information

1
From the Department of Anesthesiology (S.T., C.X., W.Z., J.W., C.N.S., N.G., A.E.M.), the McKnight Brain Institute (N.G., C.S., A.E.M.), and Department of Physiology and Functional Genomics (C.S.), University of Florida College of Medicine, Gainesville, Florida.

Abstract

BACKGROUND:

The authors studied whether neonatal propofol anesthesia affects development of the endocrine and neural systems.

METHODS:

Sprague-Dawley rats were anesthetized using intraperitoneal propofol for 5 h on postnatal days (P) 4, 5, or 6. Pups that received either saline or intralipid, but not those in the negative control groups, were also maternally separated for 5 h. Serum levels of corticosterone were measured immediately after anesthesia and in adulthood after prepulse inhibition of acoustic startle testing (≥P80), followed by measurement of hippocampal neuronal activity.

RESULTS:

Propofol acutely increased corticosterone levels to 146.6 ± 23.5 ng/ml (n = 6) versus 16.4 ± 3.5 ng/ml (n = 6) and 18.4 ± 3.2 ng/ml (n = 6) in saline- and intralipd-treated pups, respectively. In adulthood, the propofol group exhibited exacerbated endocrine responses to stress in a form of increased corticosterone levels (1,171.58 ± 149.17 ng/ml [n = 15] vs. 370.02 ± 36.01 ng/ml [n = 10] in the saline group). The propofol group had increased the frequency of miniature inhibitory postsynaptic currents in CA1 neurons of male and female rats, but reduced prepulse inhibition of startle was detected only in males. The Na-K-2Cl cotransporter inhibitor bumetanide, administered to pups before propofol injection, alleviated long-term endocrine and prepulse inhibition abnormalities. Exogenous corticosterone, administered to naive pups, induced synaptic and endocrine but not prepulse inhibition effects, similar to those of propofol.

CONCLUSION:

Propofol-caused acute increases in corticosterone levels and γ-aminobutyric acid type A receptor-mediated excitation at the time of anesthesia may play mechanistic roles in development of exacerbated endocrine responses to stress and neurobehavioral abnormalities.

PMID:
24992523
PMCID:
PMC4206572
DOI:
10.1097/ALN.0000000000000366
[Indexed for MEDLINE]
Free PMC Article

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