Nestin Overexpression Precedes Caspase-3 Upregulation in Rats Exposed to Controlled Cortical Impact Traumatic Brain Injury

Authors

Yuji Kaneko, University of South Florida
Naoki Tajiri, University of South Florida
Seongjin Yu, University of South Florida
Takuro Hayashi, University of South Florida
Christine E. Stahl, MacDill Air Force Base
Eunkyung Bae, University of South Florida
Humberto Mestre, University of South Florida
Nicholas Franzese, University of South Florida
Antonio Rodrigues Jr., University of South Florida
Maria C. Rodrigues, University of South Florida
Hiroto Ishikawa, University of South Florida
Kazutaka Shinozuka, University of South Florida
Whitney Hethorn, University of South Florida
Nathan Weinbren, University of South Florida
Loren E. Glover, University of South Florida
Jun Tan, University of South Florida
Anilkumar Harapanahalli Achyuta, Draper Laboratory
Harry van Loveren, University of South FloridaFollow
Paul R. Sanberg, University of South FloridaFollow
Sundaram Shivsankar, Draper Laboratory
Cesar V. Borlongan, University of South FloridaFollow

Document Type

Article

Publication Date

2012

Keywords

Cell proliferation, Neurogenesis, Apoptosis, Head trauma, Nestin, Caspase-3

Digital Object Identifier (DOI)

https://doi.org/10.3727/215517912X639306

Abstract

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 and then euthanized 1–48 h 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 h post-TBI, then significantly peaked at 8 h, but thereafter reverted to pre-TBI levels. On the other hand, caspase-3 mRNA expression was slightly elevated at 8 h post-TBI, which did not become significantly upregulated until 48 h. Immunofluorescent microscopy revealed a significant surge in nestin-immunoreactive cells in the cortex, corpus callosum, and subventricular zone at 24 h 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 h. These results suggest that the injured brain attempts to repair itself via cell proliferation immediately after TBI but 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.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Cell Medicine, v. 4, issue 2, p. 55-63

Scholar Commons Citation

Kaneko, Yuji; Tajiri, Naoki; Yu, Seongjin; Hayashi, Takuro; Stahl, Christine E.; Bae, Eunkyung; Mestre, Humberto; Franzese, Nicholas; Rodrigues, Antonio Jr.; Rodrigues, Maria C.; Ishikawa, Hiroto; Shinozuka, Kazutaka; Hethorn, Whitney; Weinbren, Nathan; Glover, Loren E.; Tan, Jun; Achyuta, Anilkumar Harapanahalli; van Loveren, Harry; Sanberg, Paul R.; Shivsankar, Sundaram; and Borlongan, Cesar V., "Nestin Overexpression Precedes Caspase-3 Upregulation in Rats Exposed to Controlled Cortical Impact Traumatic Brain Injury" (2012). Neurosurgery and Brain Repair Faculty Publications. 60.
https://digitalcommons.usf.edu/nbr_facpub/60