Affordable Access

deepdyve-link
Publisher Website

FGF-2 Attenuates Neuronal Apoptosis via FGFR3/PI3k/Akt Signaling Pathway After Subarachnoid Hemorrhage.

Authors
  • Okada, Takeshi1, 2
  • Enkhjargal, Budbazar1
  • Travis, Zachary D1
  • Ocak, Umut1
  • Tang, Jiping1
  • Suzuki, Hidenori2
  • Zhang, John H3, 4
  • 1 Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St, Loma Linda, CA, 92354, USA.
  • 2 Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. , (Japan)
  • 3 Department of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St, Loma Linda, CA, 92354, USA. [email protected]
  • 4 Department of Anesthesiology, Loma Linda University, Risley Hall, Room 219, 11041 Campus St, Loma Linda, CA, 92354, USA. [email protected]
Type
Published Article
Journal
Molecular neurobiology
Publication Date
Dec 01, 2019
Volume
56
Issue
12
Pages
8203–8219
Identifiers
DOI: 10.1007/s12035-019-01668-9
PMID: 31203572
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Neuronal apoptosis is a common and critical pathology following subarachnoid hemorrhage (SAH). We investigated the anti-apoptotic property of fibroblast growth factor (FGF)-2 after SAH in rats. A total of 289 rats underwent endovascular perforation to induce SAH or sham operation. Three dosages (3, 9, or 27 μg) of recombinant FGF-2 (rFGF-2) or vehicle was administered intranasally to rats 30 min after SAH induction. The pan-FGF receptor (FGFR) inhibitor PD173074 or vehicle was administered intracerebroventricularly (i.c.v.) 1 h before modeling, in addition to rFGF-2 treatment. Small interfering ribonucleic acid (siRNA) for FGFR1 and FGFR3 or scrambled siRNA was administered i.c.v. 48 h before SAH induction in addition to rFGF-2 treatment. Anti-FGF-2 neutralizing antibody or normal mouse immunoglobulin G (IgG) was administered i.c.v. 1 h before SAH model. Neurobehavioral tests, SAH severity, brain water content, immunofluorescence, Fluoro-Jade C, TUNEL staining, and western blot were evaluated. The expression of FGF-2, FGFR1, and FGFR3 increased after SAH. FGFR1 and FGFR3 were expressed in the neurons. Nine micrograms of FGF-2 alleviated neurological impairments, brain edema, and neuronal apoptosis following SAH. A rFGF-2 treatment improved motor skill learning and spatial memory and increased the number of surviving neurons postinjury to 28 days after SAH. PD173074 abolished the anti-apoptotic effects of rFGF-2 via suppression of the expression of PI3k, phosphorylated Akt (p-Akt), and Bcl-2 leading to enhancement of the expression of Bax. FGFR3 siRNA worsened neurobehavioral function and suppressed the expression of PI3k, p-Akt, and Bcl-2 rather than FGFR1 siRNA in SAH rats treated with rFGF-2. Anti-FGF-2 neutralizing antibody suppressed the expression of PI3k and p-Akt after SAH. FGF-2 may be a promising therapy to reduce post-SAH neuronal apoptosis via activation of the FGFR3/PI3k/Akt signaling pathway.

Report this publication

Statistics

Seen <100 times