Open AccessNestin Overexpression Precedes Caspase-3 Upregulation in Rats Exposed to Controlled Cortical Impact Traumatic Brain Injury
Author(s) -
Yuji Kaneko,
Naoki Tajiri,
SeongJin Yu,
Takuro Hayashi,
Christine E. Stahl,
Eun-Kyung Bae,
Humberto Mestre,
Nicholas Franzese,
António Rodrigues,
Maria Carolina O. Rodrigues,
Hiroto Ishikawa,
Kazutaka Shinozuka,
Whitney R. Hethorn,
Nathan L. Weinbren,
Loren E. Glover,
Jun Tan,
Anilkumar Harapanahalli Achyuta,
Harry van Loveren,
Paul R. Sanberg,
Sundaram Shivsankar,
Cesar V. Borlongan
Publication year - 2012
Publication title -
cell medicine
Language(s) - English
Resource type - Journals
ISSN - 2155-1790
DOI - 10.3727/215517912x639306
Subject(s) - traumatic brain injury , nestin , subventricular zone , medicine , apoptosis , downregulation and upregulation , immunohistochemistry , caspase 3 , corpus callosum , proliferation marker , cerebral cortex , pathology , programmed cell death , neuroscience , biology , neural stem cell , microbiology and biotechnology , stem cell , psychiatry , biochemistry , gene
Our understanding of biological mechanisms and treatment options for traumatic brain injury (TBI) is limited. Here, we employed quantitative real-time PCR (QRT-PCR) and immunohistochemical analyses to determine the dynamic expression of cell proliferation and apoptosis in an effort to provide insights into the therapeutic window for developing regenerative strategies for TBI. For this purpose, young adult Sprague-Dawley rats were subjected to experimental TBI using a controlled cortical impactor, then euthanized 1-48 hours after TBI for QRT-PCR and immunohistochemistry. QRT-PCR revealed that brains from TBI exposed rats initially displayed nestin mRNA expression that modestly increased as early as 1-hour post-TBI, then significantly peaked at 8 hours, but thereafter reverted to pre-TBI levels. On the other hand, caspase-3 mRNA expression was slightly elevated at 8 hours post-TBI, which did not become significantly upregulated until 48 hours. Immunofluorescent microscopy revealed a significant surge in nestin immunoreactive cells in the cortex, corpus callosum, and subventricular zone at 24 hours post-TBI, whereas a significant increase in the number of active caspase-3 immunoreactive cells was only found in the cortex and not until 48 hours. These results suggest that the injured brain attempts to repair itself via cell proliferation immediately after TBI, but that this endogenous regenerative mechanism is not sufficient to abrogate the secondary apoptotic cell death. Treatment strategies designed to amplify cell proliferation and to prevent apoptosis are likely to exert maximal benefits when initiated at the acute phase of TBI.