Suppression of Basic Fibroblast Growth Factor Expression by Antisense Oligonucleotides Inhibits Neural Stem Cell Proliferation and Differentiation in Rat models With Focal Cerebral Infarction

摘要

ABSTRACT This study is designed to investigate the role of basic fibroblast growth factor (bFGF) antisense oligonucleotide (ASODN) on the proliferation and differentiation of neural stem cells (NSCs) in rat models with focal cerebral infarction (CI). Seventy‐five Sprague‐Dawlay (SD) rats were randomly divided into the control, sham, middle cerebral artery occlusion (MCAO), MCAO?+?nonsense oligonucleotide (NODN), and MCAO?+?ASODN groups. Proliferation and differentiation of NSCs were detected by bromodeoxyuridine (BrdU) and immunofluorescence staining, respectively. ELISA was performed to detect the expressions of endogenous factors that include insulin‐like growth factor 1 (IGF‐1), glial cell line derived neurotrophic factor (GDNF), brain‐derived neurotrophic factor (BDNF), transforming growth factor‐α1 (TGF‐α1), bFGF, and nerve growth factor (NGF). Results show significant neurological deficits and focal CI in the MCAO and MCAO?+?NODN groups. An obvious increase of NSC proliferation, reactive proliferation of astrocytes in CI areas, differentiation of newly proliferated NSCs into mature neuronal cells, and expressions of endogenous growth factors exhibited in the MCAO, MCAO?+?NODN and MCAO?+?ASODN groups. Compared to the MCAO and MACO?+?NODN groups, the MCAO?+?ASODN group showed a significant decrease NSC proliferation and differentiation in CI areas as well as decrease expressions of endogenous growth factors. These findings may offer insight to help us understand more as to how bFGF ASODN can effectively suppress the proliferation and differentiation of NSCs. These findings are expected to help contribute to research for new targets in the treatment of focal CI. J. Cell. Biochem. 118: 3875–3882, 2017. ? 2017 Wiley Periodicals, Inc.