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

Cell Medicine

Humberto Mestre¹  Harry Van Loveren¹  Nicholas Franzese¹  Loren E. Glover¹  Yuji Kaneko¹  Seongjin Yu¹  Antonio Rodrigues, Jr.¹  Nathan Weinbren¹  Eunkyung Bae¹  Paul R. Sanberg¹  Maria C. Rodrigues¹  Whitney Hethorn¹  Takuro Hayashi¹  Naoki Tajiri¹  Kazutaka Shinozuka¹  Cesar V. Borlongan¹  Hiroto Ishikawa¹  Anilkumar Harapanahalli Achyuta²  Sundaram Shivsankar²  Christine E. Stahl³  Jun Tan⁴ 

[1] * Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA;¶ Draper Laboratory, Bioengineering Center, Tampa, FL, USA;† Department of Aerospace Medicine, MacDill Air Force Base, Tampa, FL, USA;‡ James A. Haley Veterans' Administration Hospital, Tampa, FL, USA§ Rashid Laboratory for Developmental Neurobiology, Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa, FL, USA

关键词: Cell proliferation;    Neurogenesis;    Apoptosis;    Head trauma;    Nestin;    Caspase-3;   

DOI  :  10.3727/215517912X639306

学科分类：生物科学（综合）

来源: Cognizant Communication Corporation

【 摘 要 】

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.

【 授权许可】

CC BY