Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury
Bacterial endotoxin sensitizes the immature brain to hypoxic-ischaemic injury
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DOI：
10.1046/j.0953-816x.2001.01474.x
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发表时间：
2001-03-01
影响因子：
3.4
通讯作者：
Hagberg, H
中科院分区：
文献类型：
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作者：
Eklind, S;Mallard, C;Hagberg, H
流行病学研究表明，在感染和出生窒息合并暴露后，患脑瘫的风险显著增加。然而，这种脆弱性增加的内在机制仍不清楚。我们研究了低剂量细菌内毒素对未成熟大鼠脑缺氧缺血性损伤的影响。在单侧缺氧缺血前4 h给予7日龄大鼠细菌内毒素（脂多糖0.3 mg/kg），3天后测定神经功能结局。在研究期间测量直肠温度和脑血流量，并检测脑中CD 14和Toll样受体-4 mRNA的表达。我们发现，低剂量的内毒素显著地使未成熟的脑对损伤敏感，并诱导脑梗死，以响应自身不引起或很少引起损伤的短期缺氧缺血。这种效应不能用脑血流量减少或体温过高来解释。在与致敏损伤，我们发现了改变表达的CD 14 mRNA和Toll样受体-4在脑中。这些结果表明，先天免疫系统可能参与了感染和缺氧缺血组合后未成熟大脑的脆弱性。
Epidemiological studies show a markedly increased risk of cerebral palsy following the combined exposure of infection and birth asphyxia. However, the underlying mechanisms of this increased vulnerability remain unclear. We have examined the effects of a low dose of bacterial endotoxin on hypoxic-ischaemic injury in the immature brain of rats. Bacterial endotoxin (lipopolysaccharide 0.3 mg/kg) was administered to 7-day-old rats 4 h prior to unilateral hypoxia-ischaemia and the neurological outcome was determined 3 days later. Rectal temperature and cerebral blood flow was measured during the study and the expression of CD14 and toll-like receptor-4 mRNA in the brain was examined. We found that a low dose of endotoxin dramatically sensitizes the immature brain to injury and induces cerebral infarction in response to short periods of hypoxia-ischaemia that by themselves caused no or little injury. This effect could not be explained by a reduction in cerebral blood flow or hyperthermia. In association with the sensitization of injury we found an altered expression of CD14 mRNA and toll-like receptor-4 mRNA in the brain. These results suggest that the innate immune system may be involved in the vulnerability of the immature brain following the combination of infection and hypoxia-ischaemia.