Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis
Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis
复制标题
DOI：
10.1086/426399
复制
发表时间：
2005-01-01
影响因子：
6.4
通讯作者：
Leib, SL
中科院分区：
文献类型：
--
作者：
Bifrare, YD;Kummer, J;Leib, SL
背景脑源性神经营养因子（BDNF）阻断caspase-3的激活，减少骨化诱导因子（AIF）的移位，减弱谷氨酸的兴奋毒性，并增加抗氧化酶的活性。脑源性神经营养因子的神经保护机制提示脑源性神经营养因子可能对细菌性脑膜炎有益。为了评估BDNF在细菌性脑膜炎中的辅助治疗的潜在有益作用，将患有由肺炎链球菌或B族链球菌（GBS）引起的实验性脑膜炎的11日龄幼鼠随机分配接受脑池内注射BDNF（3 mg/kg）或等体积（10穆尔）的盐水。感染后22小时，通过组织形态计量学检查分析大脑皮质和海马神经元损伤的程度。与盐水治疗相比，BDNF治疗显著降低了该疾病模型中3种不同形式的脑细胞损伤的程度：GBS所致脑膜炎中的皮质坏死（中位数，0.0% [范围，0.0%-33.7%] vs. 21.3% [范围，0.0%-55.3%]; P <0.03），S.肺炎（中位数评分，0.33 [范围，0.0-1.0]对1.10 [0.10-1.56]; P <0.05）和GBS引起的脑膜炎中半胱天冬酶-3非依赖性海马细胞死亡（中位数评分，0 [范围，0-2]对0.88 [范围，0-3.25]; P <0.02）。最后一种损伤形式与AIF的核转位有关。BDNF有效地减少了细菌性脑膜炎中多种形式的神经元损伤，并可能成为这种疾病的持续治疗方法。
Background. Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis.Methods. To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 muL) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury.Results. Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P < .03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P < .05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P < .02). The last form of injury was associated with nuclear translocation of AIF.Conclusion. BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.