Fgf2 improves functional recovery—decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury

Abstract

ObjectivesA major impediment for recovery after mammalian spinal cord injury (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding factors that may reduce glial scarring, increase neuronal survival, and promote neurite outgrowth are of major importance for improving the outcome after SCI. Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume and improve functional outcome; however, the mechanisms by which this is mediated are still largely unknown.MethodsIn this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.ResultsFgf2 treatment decreased the expression of TNF-a at the lesion site, decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced astrocytes to adopt a polarized morphology and increased expression of radial markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore, Fgf2 treatment promotes the formation of parallel glial processes, “bridges,” at the lesion site that enable regenerating axons through the injury site. Additionally, Fgf2 treatment increased Sox2-expressing cells in the gray matter and neurogenesis around and at the lesion site. Importantly, these effects were correlated with enhanced functional recovery of the left paretic hind limb.ConclusionsThus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response.

An unsound AAN Practice Advisory on poststroke etanercept

“…Observers have included non-neurological medical practitioners, nurses, speech pathologists and neuroscientists, and indeed the author of this editorial. A parallel outcome has apparently been reported independently (https://www.youtube.com/ watch?v=VGuBMroX7c8) by a Stanford group [10] by injecting stem cells known to generate a cytokine with anti-TNF activity into the brain [11,12]. These as yet uncontrolled observations reinforce each other, and are both highly plausible from the TNF literature.…”

Sustained-release of FGF-2 from a hybrid hydrogel of heparin-poloxamer and decellular matrix promotes the neuroprotective effects of proteins after spinal injury

“…A previous report that evaluated the effect of FGF2 in a hemisection rat SCI model indicated that the effect of FGF2 on SCI is related to inhibited inflammation, lower production of CSPG, and increased glial processes. 5 However, the effect of FGF2 on SCI was associated with the proliferation, morphogenesis, and apoptosis of various cell populations, particularly astrocytes and neural cells, via complex signal transduction pathways in these studies. [6][7][8] The beneficial effects of FGF2 on SCI were correlated with neuronal regeneration and functional recovery.…”

A critical review of cell culture strategies for modelling intracortical brain implant material reactions

“…This indicates dual roles for bFGF in regulating GFAP expression in vivo between immature and mature CNS tissue. Concurrent with the effects bFGF has on GFAP expression in astrocytes, it has been implicated in regulating and promoting neuronal differentiation during fetal development [209] and survival post traumatic injury [210] (for a brief review of bFGF effects post CNS injury see Adeeb & Mortazavi [47]). Thus, the effect of bFGF on cultured astrocytes and neurons is paradoxical promoting a reactive astrocyte phenotype however simultaneously promoting neuronal survival.…”

“…These changes are in part regulated by an array of growth factors, cytokines and chemokines. Growth factors include fibroblast growth factors (FGF) and receptors (FGFR) [24,45,46], and transforming growth factor-b (TGF-b) and receptors [26,39], while the principle cytokines and chemokines include tumor necrosis factor alpha (TNFa) [47] and interleukins [26]. The complex interplay of these and other factors dynamically regulate the microenvironment of the lesion penumbra, which can either preserve function or lead to dysfunction; such changes occur due to promotion or inhibition of the neural network and glial cell remodeling, respectively.…”