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Original Paper

Free Access

Regional and Temporal Profiles of Calpain and Caspase-3 Activities in Postnatal Rat Brain following Repeated Propofol Administration

Milanovic D.a · Popic J.a · Pesic V.a · Loncarevic-Vasiljkovic N.a · Kanazir S.a · Jevtovic-Todorovic V.b · Ruzdijic S.a

Author affiliations

aDepartment of Neurobiology, Institute for Biological Research, University of Belgrade, Belgrade, Republic of Serbia; bDepartment of Anesthesiology, University of Virginia Health System, Charlottesville, Va., USA

Corresponding Author

Sabera Ruzdijic, PhD

Department of Neurobiology, Institute for Biological Research

University of Belgrade, Bulevar Despota Stefana 142

RS–11060 Belgrade (Republic of Serbia)

Tel. +381 11 2078 336, Fax +381 11 2761 433, E-Mail sabir@ibiss.bg.ac.rs

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Dev Neurosci 2010;32:288–301

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Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. We investigated the effect of the general anesthetic propofol on the brain of 7-day-old (P7) Wistar rats during the peak of synaptic growth. Caspase and calpain protease families most likely participate in neuronal cell death. Our objective was to examine regional and temporal patterns of caspase-3 and calpain activity following repeated propofol administration (20 mg/kg). P7 rats were exposed for 2, 4 or 6 h to propofol and killed 0, 4, 16 and 24 h after exposure. Relative caspase-3 and calpain activities were estimated by Western blot analysis of the proteolytic cleavage products of α-II-spectrin, protein kinase C and poly(ADP-ribose) polymerase 1. Caspase-3 activity and expression displayed a biphasic pattern of activation. Calpain activity changed in a region- and time-specific manner that was distinct from that observed for caspase-3. The time profile of calpain activity exhibited substrate specificity. Fluoro-Jade B staining revealed an immediate neurodegenerative response that was in direct relationship to the duration of anesthesia in the cortex and inversely related to the duration of anesthesia in the thalamus. At later post-treatment intervals, dead neurons were detected only in the thalamus 24 h following the 6-hour propofol exposure. Strong caspase-3 expression that was detected at 24 h was not followed by cell death after 2- and 4-hour exposures to propofol. These results revealed complex patterns of caspase-3 and calpain activities following prolonged propofol anesthesia and suggest that both are a manifestation of propofol neurotoxicity at a critical developmental stage.

© 2010 S. Karger AG, Basel


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    External Resources
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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: March 30, 2010
Accepted: June 14, 2010
Published online: August 12, 2010
Issue release date: December 2010

Number of Print Pages: 14
Number of Figures: 7
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

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