| The cardinal feature of brain damage in the preterm infant is the injury to hemispheric white matter. White matter damage ( WMD) has the high incidence and bad prognosis. Oligodendrocytes (OL) progenitors are particularly high in number within the developing white matter. They are in the stage of activate differentiation, and this maturation - dependent vulnerability of preoligodendro-cytes to many stimulus appears to be related to such factors as deficient antiox-dant defenses and acquisition of iron for differentiation. The fiber tracts constituting white matter being relatively unmyelinated at birth, the gray/white matter distinction is less evident in newborn infants, particularly those born preterm. Leviton and Paneth had suggested in 1990 that the process of myelination could be more susceptible to injury than the maintenance of already formed myelin, and this could account for the prominence of white matter injury in the preterm infant. Although the pathogenesis of the damage has not been clearly known yet, it was proposed that hypoxic - ischemic insult, intrauterine infection in the peri-natel period contributed to the periventricular leukomalacia( PVL) , which were the main risk clinical factors of WMD. Because of the increase of the incidence of WMD in neonates who develop the septicemia or whose mothers have been infected , currently, it was regarded that the inflammatory cytokines in response to intrauterine infection (IUI) played a key role in WMD and cerebral palsy.Amount of clinical and animal experiments proved that IUI and inflammma-tory response were the important risk factors resulting in WMD. IUI is the major reason in chorioamnionitis and prelabor rupture of membranes. Chorioamnionitiswhich is often subclinical state has little effect on the pregnant woman but has severely injury to the fetus and neonates. Clinical research suggested that WMD closely related to chorioamnionitis. The level of IL - 1, IL - 6, TNF -α rose in amniotic fluid, umbilical cord plasma whose mother developed chorioamnionitis.During the course of intrauterine fetal infection, microbial products could stimulate circulating fetal mononuclear cells to produce IL -1 (3 and tumor necrosis factor, which could increase the permeability of the blood - brain barrier and allow passage of microbial products (ie. lipopolysaccharide LPS) and cytokines into the central nervous system. The production of inflammatory cytokines IL -1, IL - 6, and TNF -α has been reported in activated and LPS - stimulated mi-croglia and these cells, in paticular, are the major sourse of TNF -α within the central nervous system. IL - 1 p, IL - 6 and TNF -α are well - characterized early reponse cytokines in inflammation, which may participate in neonatal central nervous system damage by inducing the production of other inflammatory and cytotoxic mediators, promoting leukocyte infiltration, expression of adhesion molecules , influencing glial gene expression and causing damage to OL. LPS - mediated damage to the developing white matter and a specific receptor for LPS on microglia, Toll - like receptor 4 ( TLR4) was found to be important in mediating the injury. LPS may activate the innate immune system through interaction with TLRS on immune cells. LPS binds to a protein ( CD14) that facilitates activation of TLR4, which in turn, initiates a cascade of intracellular events resulting in NF - kB activation and production of pro/inflammatory cytokines. Injury of these pro/inflam - matory cytokines to cultured OL may be induced by macro-phages either directly, or via induction of 'death' receptors such as Fas or TN-FR -1 expressed on the surface of OL. And so, the inflammatory response mediated by TNF -α may be one of the essential reasons. Due to their strong anti - inflammatory properties, dexamethasone was used as one way of therapeutic intervention in current study.IUI is the main reason for WMD. Currently, the animal models of WMD could be induced by antenatal injection of the bacteria(ie, E. coli) , virus, microbial products (ie,...
|
PDF Full Text Request