Document Detail

General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain.
MedLine Citation:
PMID:  16738805     Owner:  NLM     Status:  MEDLINE    
Brain-derived neurotrophic factor (BDNF) is important in supporting neuronal development. BDNF imbalance due to excessive neuronal inhibition can result in the apoptotic degeneration of developing neurons. Since general anesthetics cause profound depression of neuronal activity and are known to induce widespread degeneration in the developing brain, we studied their potential to activate BDNF-mediated developmental neuroapoptosis. When P7 rats (at the peak of brain development) were exposed to a commonly-used and highly pro-apoptotic anesthesia protocol (midazolam, isoflurane, nitrous oxide) for a period of 2, 4 or 6 h, we found that anesthesia modulates the key steps in BDNF-activated apoptotic cascade in two of the most vulnerable brain regions--cerebral cortex and thalamus in time-dependent fashion by activating both Trk-dependent (in thalamus) and Trk-independent p75NTR dependent (in cerebral cortex) neurotrophic pathways. beta-estradiol, a sex hormone that upregulates the protein levels of the activated Akt, protects against anesthesia-induced neuroapoptosis.
Lucy X Lu; Jun-Heum Yon; Lisa B Carter; Vesna Jevtovic-Todorovic
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  11     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-20     Completed Date:  2006-12-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1603-15     Citation Subset:  IM    
Department of Anasthesiology, University of Virginia Health System, P.O. Box 800710, Charlottesville, 22908, USA.
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MeSH Terms
Anesthesia, General / adverse effects*
Anesthetics / adverse effects,  pharmacology
Apoptosis / drug effects*,  physiology
Brain / drug effects,  growth & development*
Brain-Derived Neurotrophic Factor / metabolism,  physiology*
Cerebral Cortex / drug effects,  growth & development
Down-Regulation / drug effects
Estradiol / pharmacology
Models, Biological
Nerve Degeneration / chemically induced
Neurons / drug effects*
Oncogene Protein v-akt / metabolism
Oncogene Proteins / metabolism
Rats, Sprague-Dawley
Respiratory Insufficiency / chemically induced
Signal Transduction / drug effects
Thalamus / drug effects,  growth & development
Grant Support
Reg. No./Substance:
0/Anesthetics; 0/Brain-Derived Neurotrophic Factor; 0/Oncogene Proteins; 0/oncogene protein trk; 50-28-2/Estradiol; EC Protein v-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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