Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig
Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig
复制标题
猪弥漫性脑损伤后轴突中神经丝亚型积累的演变。
DOI：
10.1097/00005072-199906000-00003
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发表时间：
1999-06-01
影响因子：
3.2
通讯作者：
Smith, DH
中科院分区：
文献类型：
--
作者：
Chen, XH;Meaney, DF;Smith, DH
虽然神经丝蛋白在轴突中的积聚已被认为是脑创伤的一个显著特征，但特定的神经丝蛋白亚型积聚的时间过程尚未很好地确定。在本研究中，17只小型猪造成非冲击性惯性脑损伤。分别于伤后3h、6h、24h、3d、7d、10d用免疫组织化学方法检测神经营养因子-轻型(NF-Light，NF-LIGH)的轴突积聚、中性核因子(NF-M)、重核(Heavy，NF-H)的杆状和侧臂结构域及侧臂磷酸化状态。结果发现，伤后6h，损伤轴突中可见核因子-L的积聚，但直到伤后3d才能清晰地观察到核因子-M和H的积聚。此外，核因子-M和H的轴突堆积似乎主要由侧臂结构域组成。虽然我们发现积累的氮主要是去磷酸化的，但我们也检测到了磷酸化的氮的积累。最后，我们发现，发展的轴突病理可能进展为轴突切断并形成离散的终末球状结构，或者发展为围绕长轴突的静脉曲张肿胀。这些发现表明，在最初的脑损伤后，神经营养因子亚型的分解、去磷酸化和轴突积聚有不同的时间进程，这些过程发生在成熟轴突病理的形态上不同的表型中。
Although accumulation of neurofilament (NF) proteins in axons has been recognized as a prominent feature of brain trauma, the temporal course of the accumulation of specific NF subtypes has not been well established. In the present study, 17 miniature swine were subjected to nonimpact inertial brain injury. At 3 hours (h), 6 h, 24 h, 3 days, 7 days, and 10 days post-trauma, immunohistochemical analysis was performed to determine axonal accumulation of NF-light (NF-L), the rod and sidearm domains and sidearm phosphorylation states of NF-medium (NF-M), and heavy (NF-H). We found that NF-L accumulation was easily identified in damaged axons by 6 h post-trauma, but NF-M and H accumulation was not clearly visualized until 3 days following injury. In addition, the axonal accumulation of NF-M and H appeared to be primarily comprised of the sidearm domains. While the accumulating NF was found to be predominantly dephosphorylated, we also detected accumulation of phosphorylated NF. Finally, we found that developing axonal pathology may proceed either towards axotomy with discrete terminal bulb formation or towards the development of varicose swellings encompassing long portions of axons. These findings suggest that there is a differential temporal course in NF subtype disassembly, dephosphorylation, and accumulation in axons following initial brain trauma and that these processes occur in morphologically distinct phenotypes of maturing axonal pathology.