Kasselman Lora J, Sideris Alexandra, Bruno Chantal, Perez William R, Cai Ning, Nicoletti Jamee N, Wiegand Stanley J, Croll Susan D
Neuropsychology Doctoral Subprogram, Graduate Center of the City University of New York, USA.
J Neuroimmunol. 2006 Jun;175(1-2):118-27. doi: 10.1016/j.jneuroim.2006.03.008. Epub 2006 Apr 24.
Nerve growth factor (NGF) plays a role in sympathetic neuron integrity and survival. Brain-derived neurotrophic factor (BDNF) also has trophic effects on sympathetic neurons. We report here the serendipitous finding that co-treatment of hippocampus with BDNF and the NGF antagonist TrkA-Fc leads to perivascular inflammation and marked vasoconstriction. This effect is not observed with either reagent alone or in combination with other control proteins. Because NGF supports sympathetic neuron health, we tested the hypothesis that BDNF combined with sympathetic compromise caused this effect. Superior cervical ganglia were removed bilaterally with concurrent BDNF infusion into hippocampus. Perivascular inflammation was observed at 3 days, but not 12 days post treatment, when sympathetic terminals had receded, suggesting that the presence of these terminals was necessary for inflammation. Since sympathetic dysfunction may lead to compensatory overactivity of norepinephrine (NE) signaling, we co-infused BDNF with NE in the hippocampus and observed perivascular inflammation. In humans, sympathetic overactivity has been reported in a variety of vascular diseases. Some of these diseases, e.g. primary Raynaud's, are not accompanied by serious inflammatory disease whereas others, such as scleroderma and systemic lupus, are. We speculate that BDNF may contribute to the transformation of sympathetic dysfunction to inflammatory disease.
神经生长因子（NGF）在交感神经元的完整性和存活中发挥作用。脑源性神经营养因子（BDNF）对交感神经元也有营养作用。我们在此报告一项意外发现，即海马体同时接受BDNF和NGF拮抗剂TrkA-Fc处理会导致血管周围炎症和明显的血管收缩。单独使用任何一种试剂或与其他对照蛋白联合使用时均未观察到这种效应。由于NGF支持交感神经元的健康，我们检验了BDNF与交感神经损伤相结合导致这种效应的假说。双侧切除颈上神经节，同时向海马体注入BDNF。在治疗后3天观察到血管周围炎症，但在12天未观察到，此时交感神经末梢已经消退，这表明这些末梢的存在是炎症发生所必需的。由于交感神经功能障碍可能导致去甲肾上腺素（NE）信号的代偿性过度激活，我们在海马体中同时注入BDNF和NE，并观察到血管周围炎症。在人类中，多种血管疾病都有交感神经活动过度的报道。其中一些疾病，如原发性雷诺病，不伴有严重的炎症性疾病，而其他疾病，如硬皮病和系统性红斑狼疮，则伴有炎症。我们推测BDNF可能有助于交感神经功能障碍向炎症性疾病的转变。
