Suramin Inhibits Gliosis
Suramin disrupts the gliotic response following a stab wound injury to the adult rat brain.
Nicholas A. Di Prospero, Xi-Ren Zhou, Sally Meiners, Shu-Yin Ho, and Herbert M. Geller
Reactive gliosis, observed in numerous pathological states, leads to the formation
of a glial scar which is believed to impede axonal regeneration. Astrocyte reactivity can be
initiated both in vitro and in vivo by various cytokines and results in a highly metabolic state.
Thus, the aim of this study was to investigate if suramin, a polysulfanated napthylurea, which has
been shown to inhibit the binding of many different cytokines to their cell surface receptors as well
as downregulating cellular activity, could attenuate the glial response after brain injury. Suramin
(5µl, 75µM) or saline vehicle was injected intracerebrally through the same needle used to make the stab
wound at the time of lesioning. Suramin-treated animals showed an obvious reduction in several parameters
of CNS inflammation: cellular proliferation, GFAP levels, and tenascin immunoreactivity were reduced
in suramin-treated as compared to control animals at early time points. GFAP immunoreactivity was
strikingly reduced at 3 days after injury as confirmed by Western blot analysis. This reduction was
transient, however, in that the difference in GFAP expression between suramin-treated and control animals
was less apparent at 7 days and had disappeared by 30 days after injury. Likewise, fewer BrdU positive
cells were noted in treated versus control tissue at 1 and 3 days but this difference was not significant
by 7 days. Moreover, tenascin immunoreactivity was greatly diminished at 24 hours in suramin-treated lesion
areas, which is analogous to our observations that suramin can antagonize tenascin expression by cultured
astrocytes treated with bFGF. These results demonstrate that a single injection of suramin transiently
inhibits the gliotic response and may allow assessment of the inhibitory role of reactive astrocytes in CNS
recovery.
Return to Publications