Transient axonal injury in the absence of demyelination:: A correlate of clinical disease in acute experimental autoimmune encephalomyelitis
Transient axonal injury in the absence of demyelination:: A correlate of clinical disease in acute experimental autoimmune encephalomyelitis
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DOI：
10.1007/s00401-006-0047-y
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发表时间：
2006-06-01
影响因子：
12.7
通讯作者：
Bradl, M
中科院分区：
文献类型：
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作者：
Aboul-Enein, F;Weiser, P;Bradl, M
轴突变性导致多发性硬化症（一种中枢神经系统的炎性疾病）中出现的短暂和永久性神经功能缺损。为了研究引起轴突变性的免疫机制，我们在野生型刘易斯大鼠和刘易斯大鼠中诱导了实验性自身免疫性脑脊髓炎（EAE），由于蛋白脂质蛋白（PLP）过度表达导致髓鞘变性缓慢进行。EAE由致脑炎性T细胞单独转移或T细胞与脱髓鞘抗体共同转移引发。血管周围巨噬细胞中诱导型一氧化氮合酶（iNOS）的表达与轴突的短暂功能障碍有关，反映了淀粉样前体蛋白的局灶性和可逆性积累。临床疾病与APP阳性轴突球体的数量相关。脱髓鞘与巨噬细胞中iNOS表达的进一步增加和更高程度的轴突损伤相关。我们的研究表明，一氧化氮及其代谢产物有助于轴突病理学，也可能是随后的神经功能障碍的EAE。
Axonal degeneration contributes to the transient and permanent neurological deficits seen in multiple sclerosis, an inflammatory disease of the central nervous system. To study the immunological mechanisms causing axonal degeneration, we induced experimental autoimmune encephalomyelitis (EAE) in wildtype Lewis rats and Lewis rats with a slowly progressive myelin degeneration due to proteolipid protein (PLP) overexpression. EAE was triggered either by the transfer of encephalitogenic T-cells alone or by the co-transfer of T-cells with demyelinating antibodies. Inducible nitric oxide synthase (iNOS) expression in perivascular macrophages was associated with a transient functional disturbance of axons, reflected by the focal and reversible accumulation of amyloid precursor protein. Clinical disease correlated with the numbers of APP positive axon spheroids. Demyelination was associated with a further increase of iNOS expression in macrophages and with a higher degree of axonal injury. Our studies suggest that nitric oxide and its metabolites contribute to axonal pathology and possibly also to subsequent neurological dysfunction in EAE.