Suramin disrupts the gliotic response following a stab wound injury to the adult rat brain.
Reactive gliosis, observed in numerous pathological states, leads to the formation of a glial scar that is believed to impede axonal regeneration. Astrocyte reactivity can be initiated both in vitro and in vivo by various cytokines. Thus, the aim of this study was to investigate if suramin, a polysulfonated napthylurea that has been shown to inhibit the binding of many different cytokines to their cell surface receptors, could attenuate the glial response after brain injury. A single dose of suramin (5 microl, 75 microM) 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-C 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 significantly diminished at 24 h as confirmed by Western blot analysis in suramin-treated lesion areas, which is analogous to our observations that suramin can antagonize tenascin expression by cultured astrocytes treated with bFGF. In addition, examination of the corpus callosum of saline-treated animals 30 days post-trauma revealed a disruption of the fiber tract within the lesion site, while suramin-treated animals displayed numerous fibers spanning the lesion. These results demonstrate that a single injection of suramin transiently inhibits the gliotic response, which may be sufficient to ameliorate subsequent tissue damage.
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
N A
NA
Di Prospero
X R
XR
Zhou
S
S
Meiners
W G
WG
McAuliffe
S Y
SY
Ho
H M
HM
Geller
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013498:Suramin / Q000494:pharmacology*; D019063:Tenascin / Q000378:metabolism; D014951:Wounds, Stab / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D019063:Tenascin; D013498:Suramin; D005346:Fibroblast Growth Factors