Abstract
Fibroblast growth factor-2 is a pleiotrophic cytokine with neurotrophic and gliogenic properties. It is known to regulate CNS injury responses, which include transformation of reactive astrocytes, neurogenesis, and promotion of neurotrophic activities. In the brain, it is localized in astrocytes and discrete neuronal populations. Following both central and peripheral nervous system injury, astrocytes become reactive. These activated cells undergo hypertrophy. A key indicator of astrocyte activation is the increased accumulation of intermediate filaments composed of glial fibrillary acidic protein (GFAP). Following physical insult of brain or spinal cord, reactive astrocytes show increased FGF-2 immunoreactivity. Thus, FGF-2 appears to participate in astrocytic differentiation and proliferation and a good candidate for astrocytic function regulation in healthy, injured, or diseased CNS. To further investigate the cellular mechanisms underlying FGF-2 restorative actions and to analyze the changes within astroglial cells, we studied the localization of GFAP and FGF-2 in adult intact and injured Pleurodeles CNS. Our results show that spinal cord injury triggers a significant increase in FGF-2 immunoreactivity in reactive astrocytes at sites of insult. In addition, these results were time-dependent. Increase in FGF-2 immunoreactivity along the CNS axis, starting 1-week post-injury, was long-lasting extending to 6 weeks. This increase was accompanied by an increase in GFAP immunoreactivity in the same spatial pattern except in SC3 where its level was almost similar to sham-operated animals. Therefore, we suggest that FGF-2 may be involved in cell proliferation and/or astroglial cells differentiation after body spinal cord transection, and could thus play an important role in locomotion recovery.
Highlights
Spinal cord and brain injuries in humans usually result in crippling conditions because of the limited ability of repair in the mammalian central nervous system (CNS)
In order to understand fibroblast growth factor-2 (FGF-2) expression dynamics during Pleurodeles CNS spontaneous regeneration in vivo, we studied its spatio-temporal localization in astrocyte populations using glial fibrillary acidic protein (GFAP) as a marker (Reeves et al, 1989) following spinal cord complete transection at the mid-trunk region
We investigated FGF-2 and GFAP immunoreactivity in order to characterize the cellular localization of these proteins in the spinal cord after lesion
Summary
Spinal cord and brain injuries in humans usually result in crippling conditions because of the limited ability of repair in the mammalian central nervous system (CNS). The initial event of spinal cord regeneration is the induction of migratory behavior in the cells that line the central canal rostral to the plane of amputation (Edgar and Singer, 1972; Nordlander and Singer, 1978; Arsanto et al, 1992; O’Hara et al, 1992), the ependymal cells. These cells retain the structure of radial glial cells throughout life (Holder et al, 1990). Several studies suggest that the regeneration processes of the spinal cord occurring after body transection and tail amputation are different (Chernoff et al, 2003)
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