A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury

Abstract

Traumatic injury to the CNS initiates transient and unsuccessful regeneration of damaged neural pathways, accompanied by reactive gliosis, angiogenesis, and deposition of a dense fibrous glial/meningeal scar at the wound site. Basic fibroblast growth factor (basic FGF) is a CNS protein with potent effects on neurons, glia, fibroblasts, and vascular endothelial cells. Hybridization and immunocytochemical methods were used to examine temporal and spatial changes in distribution and levels of basic FGF protein and mRNA and also of its receptor mRNA (flg), following a defined wound to the cerebral cortex of adult rat brains. In the injured brain, a rapid, transient increase in basic FGF mRNA and protein is readily detectable within 7 d of surgery and thereafter declines in the tissues bordering the lesion. The increased expression is localized to multiple cell types including macrophages, neurons, astrocytes, and vascular endothelial cells. The changes in immunoreactive basic FGF parallel changes in the bioactivity of extracted heparin-binding proteins, which include basic FGF. Focal increases in flg mRNA appear 7 d after injury and subside by 14 d. The changes in local basic FGF synthesis, concentration, localization, and bioactivity suggest that this growth factor may contribute to the cascade of cellular events that occur in CNS wound repair.

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

“…A similar trend has been reported for fibrin gels loaded with VEGF and heparin. [46] The initial bFGF loading amount did not change the release kinetics significantly at the concentrations studied. Since there was an excess of BSA and heparin employed to stabilize the bFGF, the increase in the bFGF content relative to the total protein/heparin added was small and thus a minimal effect on the protein release kinetics was observed.…”

Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage

“…In demyelinating lesions such as in multiple sclerosis, high levels of FGF-2 are produced by reactive astrocytes and macrophages (GomezPinilla et al, 1992;Hinks and Franklin, 1999;Messersmith et al, 2000;Holley et al, 2003). Concomitantly, FGFR1, which is normally low or undetectable in adult white matter (Asai et al, 1993), begins to be expressed by glial cells in lesions (Logan et al, 1992). We demonstrated that application of FGF-2 to mature OLs in culture gives rise to a novel OL phenotype characterized by a downregulation of major myelin-specific proteins and loss of myelin-like membranes, increases in process length, and cell cycle reentry with no mitogenic activity (for review, see .…”

Regional differences in glial-derived factors that promote dendritic outgrowth from mouse cortical neurons in vitro

“…Could the functional diversity of astroglia, therefore, be secondary to specific localization of these substances? Immunohistochemical reactivity or mRNA expression of several growth factors including bFGF (Ferrara et al, 1988;Finklestein et al, 1988;Gonzalez et al, 1990;Gomez-Pinilla et al, 1992;Logan et al, 1992;Woodward et al, 1992), NGF (Furukawaet al, 1986;Luet al, 1991;Saadet al, 1991;Yoshida and Gage, 199 1;Zafra et al, 1992) EGF Nieto-Sampedro et al, 1988) IGF (Rotwein et al, 1988;Garcia-Estrada et al, 1992) PDGF (Mapstone, 1991;Yeh et al, 199 l), and cytokines such as TGF (Fallon et al, 1990;Wesselingh et al, 1990;Saad et al, 1991) and IL-l (Wesselingh et al, 1990) have been detected in astroglial cells both in vitro and in vivo. None of these studies, however, determined whether there are regional differences in synthesis, expression, or release ofgrowth factors from astroglial cells.…”