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

Brain and Behavior

Yona Goldshmit¹  Frisca Frisca²  Alexander R. Pinto¹  Alice Pébay³  Jean-Kitty K. Y. Tang¹  Ashley L. Siegel¹  Jan Kaslin¹ 

[1] Australian Regenerative Medicine Institute, East Melbourne, VIC, Australia;Department of Ophthalmology, The University of Melbourne, East Melbourne, VIC, Australia;Centre for Eye Research Australia & Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia

关键词: Astroglia;    GFAP;    nestin;    Pax6;    progenitors;    regeneration;    Sox2;    spinal cord injury;   

DOI  :  10.1002/brb3.172

来源: Wiley

【 摘 要 】

Abstract

Objectives

A 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.

Methods

In this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.

Results

Fgf2 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.

Conclusions

Thus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response.

【 授权许可】

CC BY   
© 2014 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

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