1 University of Toronto , Institute of Medical Science, Toronto, Ontario, Canada .
2 Division of Genetics and Development, Krembil Research Institute , Toronto, Ontario, Canada .
J Neurotrauma. 2018 Aug 15;35(16):1929-1941. doi: 10.1089/neu.2017.5495.
Current biomarker research in spinal cord injury (SCI) and traumatic brain injury has focused on a number of structural protein candidates, including the microtubule-associated protein tau. Evidence from models of traumatic brain injury has demonstrated that hyperphosphorylation of tau (p-tau) occurs in injured axons and demonstrates its utility as a biomarker for brain injury; however, the potential of p-tau as a biomarker for SCI is not yet known. Therefore, the present study determined whether tau is hyperphosphorylated in injured spinal cord axons, and then examined cerebrospinal fluid (CSF) and serum concentrations of p-tau and total-tau protein after a clinically relevant severe impact-compression SCI in rats. We found that severe SCI at T8 showed the presence of p-tau in damaged axons with a similar time course and distribution pattern to β-APP, a biomarker of axonal injury. The presence of p-tau and β-APP positive axons extended no farther than 5000 μm rostral and caudal to the injury epicenter, and was at its maximum at one day post-SCI. CSF levels of p-tau and total-tau significantly increased at one day post-SCI; however, only serum p-tau levels were significantly elevated in rats with SCI compared with naïve rats. These results suggest that CSF and serum p-tau may be a useful biomarker for severe traumatic SCI.
目前，脊髓损伤 (SCI) 和创伤性脑损伤的生物标志物研究集中在一些结构蛋白候选物上，包括微管相关蛋白 tau。创伤性脑损伤模型的证据表明，tau 发生过度磷酸化 (p-tau)，存在于损伤的轴突中，并证明其作为脑损伤生物标志物的效用；然而，p-tau 作为 SCI 生物标志物的潜力尚不清楚。因此，本研究确定 tau 是否在损伤的脊髓轴突中过度磷酸化，然后在大鼠中进行临床相关的严重撞击-压缩 SCI 后，检查脑脊液 (CSF) 和血清中 p-tau 和总 tau 蛋白的浓度。我们发现 T8 处的严重 SCI 显示受损轴突中存在 p-tau，其时间过程和分布模式与 β-APP 相似，β-APP 是轴突损伤的生物标志物。p-tau 和 β-APP 阳性轴突的存在不超过损伤中心前后 5000 μm，在 SCI 后 1 天达到最大值。SCI 后 1 天 CSF 中 p-tau 和总 tau 水平显著升高；然而，与未受伤的大鼠相比，只有 SCI 大鼠的血清 p-tau 水平显著升高。这些结果表明，CSF 和血清 p-tau 可能是严重创伤性 SCI 的有用生物标志物。
