Document Detail


Is age-dependent, ketamine-induced apoptosis in the rat somatosensory cortex influenced by temperature?
MedLine Citation:
PMID:  20298758     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
General anesthetics have long been thought to be relatively safe but recent clinical studies have revealed that exposure of very young children (4 years or less) to agents that act by blocking the N-methyl-D-aspartate receptor (NMDAR) can lead to cognitive deficits as they mature. In rodent and non-human primate studies, blockade of this receptor during the perinatal period leads to a number of molecular, cellular and behavioral pathologies. Despite the overwhelming evidence from such studies, doubt remains as to their clinical relevance. A key issue is whether the primary injury (apoptotic cell death) is specific to receptor blockade or due to non-specific, patho-physiological changes. Principal to this argument is that loss of core body temperature following NMDAR blockade could explain why injury is observed hours later. We therefore examined the neurotoxicity of the general anesthetic ketamine in P7, P14 and P21 rats while monitoring core body temperature. We found that, at P7, ketamine induced the pro-apoptotic enzyme activated caspase-3 in a dose-dependent manner. As expected, injury was greatly diminished by P14 and absent by P21. However, contrary to expectations, we found that core body temperature was not a factor in determining injury. Our data imply that injury is directly related to receptor blockade and is unlikely to be overcome by artificially changing core body temperature.
Authors:
S Gutierrez; A Carnes; B Finucane; G Musci; W Oelsner; L Hicks; G B Russell; C Liu; C P Turner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-03-15
Journal Detail:
Title:  Neuroscience     Volume:  168     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-08-20     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-62     Citation Subset:  IM    
Copyright Information:
2010 IBRO. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Department of Neurobiology & Anatomy, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157-1010, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Anesthetics, General / pharmacology*
Animals
Apoptosis*
Caspase 3 / biosynthesis
Female
Ketamine / pharmacology*
Male
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Somatosensory Cortex / cytology,  drug effects*
Temperature*
Grant Support
ID/Acronym/Agency:
R01 NS051632/NS/NINDS NIH HHS; R01 NS051632-04/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, General; 0/Receptors, N-Methyl-D-Aspartate; 6740-88-1/Ketamine; EC 3.4.22.-/Caspase 3
Comments/Corrections

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