Experimental study on cerebral white matter damage in neonatal rat after intrauterine Escherichia coli infection

Objective To investigate the expression of glial fibrillary acidic protein(GFAP), GFAP mRNA and interleukin-1β mRNA(IL-1β mRNA), tumor necrosis factor-α mRNA (TNF-α mRNA) in neonatal rat brain after intrauterine infection.Methods Escherichia coli (E.coli) was inoculated into both uterine horns of pregnant rats when gestation was 70% complete(15 days). The control group was treated with normal saline. The pups were killed on the postnatal day 1(P1), P3 and P7,respectively. The cerebral white matter damage of the neonatal rats was determined by HE staining. Immunohistochemistry was used for evaluation of GFAP expression in neonatal rat brains and RT-PCR to analyze GFAP mRNA, IL-1β mRNA and TNF-α mRNA expression at P1, P3 and P7. Results The major histopathological changes in neonatal cerebral white matter at P7 after intrauterine infections were:weak staining of cerebral white matter and focal rarefaction. GFAP-positive cells were observed in both the control and the E.coli -treated groups. The numbers of GFAP-positive cells of the E.coli -treated group pups were markedly increased in periventricular white matter and hippocampus at P7 compared with those of the control group(periventricular white matter: 9.73±3.55 vs 5.67±1.90, P 0.05 and hippocampus: 7.81±3.61 vs 2.16±1.11, P 0.05, respectively). No significantly different levels of GFAP expression in corpus callosum were found between two groups( P 0.05). The expression of GFAP mRNA in brain of the E.coli -treated neonatal rat was higher than the control at P1, P3(P1: 0.25±0.07 vs 0.15±0.08, P 0.05 and P3: 0.50±0.09 vs 0.39±0.08, P 0.05, respectively), but the expression of GFAP mRNA in brain of the neonatal rat at P7 had no significant difference between two groups( P 0.05). The expression of IL-1β mRNA and TNF-α mRNA in brain of the E. coli -treated neonatal rat were higher than of the control at P1(IL-1β mRNA: 0.83±0.19 vs 0.50±0.30, P 0.05 and TNF-α mRNA: 0.74±0.30 vs 0.30±0.20, P 0.05, respectively), but the expression of IL-1β mRNA and TNF-αmRNA in brain of the neonatal rat at P3 and P7 had no significant difference between two groups( P 0.05). Conclusions The intrauterine infection could cause neonatal white matter damage and IL-1β, TNF-α may be a mechanism mediating between the two events.