| Preterm white matter damage was the most important risk factor that associated with cerebral palsy. The major neuropathology of white matter damage consisted of white matter astrocytosis, myelination retardation and axonal damage. Although the exact mechanism involved in white matter damage is unknown, the epidemiologic evidence supported the view that infants exposed to intrauterine infection were at increased risk for white matter damage. The most important prenatal factor that associated with white matter damage appeared to be intrauterine infection. In current study, we developed a model of intrauterine infection in rats using Escherichia coli (E.coli) as the inflammatory stimulus to investigate effects of intrauterine infection on cerebral white matter in the neonatal rat brain and we examined alterations in expression of proinflammatory cytokines in the neonatal brain after intrauterine infection. The following study may present the immunological mechanisms mediating between the two events and may offer experimental basis for the future therapeutic method to ameliorate white matter damage.Objective To investigate the expression of glial fibrillary acidic protein (GFAP) , 2', 3'-cyclic nucleotide posphodiesterase (CNPase), and neurofilament (NF) and investigate the expression of interleukin-1 mRNA (IL-1 3 mRNA) and tumor necrosis factor- mRNA (TNF- mRNA) in neonatal rat brain after intrauterine infection.Methods 14 female SD rats at 70% of the gestational age (15 days) received either an intrauterine bacterial inoculum of E.coli (Infection group: n=8), or an intrauterineinjection of a sterile normal saline (Control group: n=6). The pups were killed on the postnatal day 1 (PI) , P3 and P7, respectively. Hematoxylin-eosin (HE) staining determined the cerebral white matter damage of neonatal rat at PI, P3 and P7. Irnmunohistochemistry was used for evaluation of GFAP, CNPase, and NF expression in neonatal rat brains at PI, P3 and P7. RT-PCR was used to analyze IL-1 P mRNA and TNF- a mRNA expression at PI, P3 and P7.Results Fourteen animals after intrauterine inoculation had normal food intake and activity. None was died after intrauterine inoculation. Intrauterine E.coli inoculation produced inflammation of uterine and placenta in all animals of infection group, but all cases of control group had no histologic evidence of intrauterine infection. The major histopathologic changes in neonatal cerebral white matter after intrauterine infections were as follows: weak staining of cerebral white matter and focal rarefaction, but revealed no necrotic tissue damage or obvious cavity formation. 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 marked increased in periventricular white matter and hippocampus at P7 compared with 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 significant different levels of GFAP expression in corpus callosum were found between two groups (2.89 1.73 vs 3.45 1.97, P>0.05) . The integrate density (ID) of CNPase-positive staining of the Escherichia coli-treated group pups were marked decreased in periventricular white matter and corpus callosum at P7 compared with the control group (periventricular white matter: 50.47 16.46 vs 71.77 13.24, P<0.05 and corpus callosum : 22.51 6.09 vs 32.20 8.33, P<0.05, respectively) . The ID of NF-positive staining of the Escherichia coli-treated group pups were marked decreased in periventricular white matter at P7 compared with the control group(33.31 12.67 vs 54.42 16.93, P><0.05); No significant different levels of NF expression in corpus callosum were found between two groups (20.59 5.48 vs25.38 6.16, P>0.05) . The expression of IL-1 mRNAand TNF- mRNA in brain of the E.coll-treated neonatal rat were higher than the control at PI (IL-1 mRNA: 0.83 0.19 vs 0.50 0.30, P<0.05 and TNF- mRNA: 0.74 0.30 vs 0.30 0.20, P<0.05, re... |
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