[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-1beta mRNA (IL-1beta mRNA), tumor necrosis factor-alpha mRNA (TNF-alpha 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-1beta mRNA and TNF-alpha 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-1beta mRNA and TNF-alpha mRNA in brain of the E. coli-treated neonatal rat were higher than of the control at P1 (IL-1beta mRNA: 0.83 +/- 0.19 vs 0.50 +/- 0.30, P < 0.05 and TNF-alpha mRNA: 0.74 +/- 0.30 vs 0.30 +/- 0.20, P < 0.05, respectively), but the expression of IL-1beta mRNA and TNF-alpha mRNA 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-1beta, TNF-alpha may be a mechanism mediating between the two events.
Yu
Hui-min
HM
Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Yuan
Tian-ming
TM
Tang
Hong-feng
HF
Li
Jian-ping
JP
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014599:Uterus / Q000382:microbiology*
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha