Basic Fibroblast Growth Factor Potentiates Myelin Repair Following Induction of Experimental Demyelination in Adult Mouse Optic Chiasm and Nerves

Abstract

Induction of demyelination in the central nervous system induce the oligodendrocyte progenitors to proliferate, migrate, and differentiate for restoring new myelin sheathes around demyelinated axons. Factors which increase the response of endogenous progenitor cells could be used to improve remyelination. In the current study, the effect of bFGF on lysolecithin-induced demyelination and remyelination processes in mouse optic chiasm and nerves was investigated. Lysolecithin was injected into the optic chiasm of Balb/C mice. Two groups of animals received doses of bFGF (1 or 5 ng/kg i.p.) just before and every 3 days after lysolecithin injection. Delay and amplitude of visual evoked potential (VEP) waves were recorded as indices of axonal demyelination at 7th, 13th, and 28th days post-lesion. Myelin basic protein (MBP) and Olig2 gene expressions were studied as indices of myelination and oligodendrocyte precursors' recruitment into the lesion. Lysolecithin elongated delay of P1 wave and declined the amplitude of P1-N1 wave. Lysolecithin decreased MBP and increased Olig2 expression in different days post-lesion. Lysolecithin-induced changes in VEPs were partially ameliorated by endogenous repair. bFGF reduced the increased delay, increased the reduced amplitude of P1-N1 wave, increased MBP gene expression, and accelerated the increasing pattern of Olig2. bFGF seems to be able to potentiate the endogenous repair mechanisms of myelin. Its effect on demyelination and remyelination processes seems to be mediated by oligodendrocyte progenitor cells and their differentiation to myelinating cells.

Nogo Receptor Inhibition Enhances Functional Recovery following Lysolecithin-Induced Demyelination in Mouse Optic Chiasm

“…We previously developed a focal model of demyelination in the optic chiasm of adult rats [28] and mice [29] and showed that remyelination could be followed functionally by assessing visual evoked potentials and structurally, by assessing demyelination extension [28]–[30]. Furthermore, we observed that the caudal part of the optic chiasm displayed more remyelination than the rostral part [30], probably due to its vicinity to the third ventricle, which is a known neurogenic region both in development [31] and adulthood [32]–[34].…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…Administration of exogenous growth factors such as EGF, PEDF, HGF, and CNTF in mice has been reported to enhance NSC proliferation (195,197). In addition, other factors such as bFGF, EGF, and BDNF have also been shown to enhance neurogenesis and eventually enhance functional recovery in animal models of neurological disease (198)(199)(200). Administration of valproic acid has been shown to attenuate symptoms of EAE, and increase endogenous myelin repair by recruiting NSCs and oligodendrocyte progenitors to the lesion sites (201).…”

The role of growth factors as a therapeutic approach to demyelinating disease

“…The significance of these increases has been evaluated by elevating levels of FGF2 after demyelination. Injections of FGF2 reverse deficits in myelin basic protein (MBP) gene expression and axonal function after lysolecithin treatment of the optic chiasm of adult mice (Dehghan et al 2012). It also increases MBP gene expression after lysolecithin treatment of the hippocampus of adult rats (Azin et al 2015).…”