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Barone, F.C., Arvin, B., White, R.F., Miller, A., Webb, C.L., Willette, R.N., Lysko, P.G. and Feuerstein, G.Z. (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke, 28, 1233-1244. doi:10.1161/01.STR.28.6.1233

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• TITLE: Pro-inflammatory cytokine; tumor-necrosis factor-alpha (TNF-α) inhibits astrocytic support of neuronal survival and neurites outgrowth

  AUTHORS: Ebtesam M. Abd-El-Basse

  KEYWORDS: Astrocytes; Neurons; Cytokines; Tumor-Necrosis Factor-Alpha

  JOURNAL NAME: Advances in Bioscience and Biotechnology, Vol.4 No.8B, August 8, 2013

  ABSTRACT: Reactive astrogliosis has been implicated in the failure of axonal regeneration in adult mammalian Central Nervous System (CNS). It is our hypothesis that inflammatory cytokines act upon astrocytes to alter their biochemical and physical properties, which may in turn be responsible for the failure of neuronal regeneration. We have therefore examined the effect of tumor-necrosis factor-alpha (TNF-α) on the ability of astrocytes to support the survival of the cortical neurons and the growth of the neurites. Mouse astrocytes and cortical neuronal cultures were prepared. It was observed that when neurons were cultured in absence of astrocytes only a few of them grew and survived only for 5-6 days. These neurons had small cell bodies and few, short neurites. However, when the same numbers of neurons were cultured on the top of astrocytes, more neurons grew and survived up to 16-18 days. They had bigger cell bodies and many long branched neurites that formed anestamosing networks. The neurons then coalesced and the neurites formed thick bundles. When the same numbers of neurons were grown on the top of astrocytes pre-treated with TNF-α, few neurons survived up to 13 days. The neurites of the survived neurons were shorter than neurites of neurons grown on normal astrocytes and did not form bundles. In addition, TNF-α stimulated the expression of glial fibrillary acidic protein (GFAP) by astrocytes. These results support that the pro-inflammatory cytokine, TNF-α modulates the gliosis and that the astrocytic cell supports neuronal survival and neurite outgrowth.