From the National Institute of Nursing Research (V.A.G., C.L., C.D., J.M.G.), National Institute of Neurological Disorders and Stroke (P.S.), and Center for Neuroscience and Regenerative Medicine (P.S., J.M.G.) and Department of Neurology (K.K., B.-X.Q.), Uniformed Services University of the Health Sciences, NIH; Walter Reed National Military Medical Center (K.K.), National Intrepid Center of Excellence, Bethesda, MD; Department of Physical Medicine & Rehabilitation (W.C.W.), Virginia Commonwealth University, Richmond; RTI International (T.N.), Research Triangle Park, NC; and Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia.
Neurology. 2020 Jun 9;94(23):e2412-e2423. doi: 10.1212/WNL.0000000000009577. Epub 2020 May 27.
To measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms.
Exosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1-2 mTBIs, and repetitive (3 or more) mTBIs.
Elevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF.
Repetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.
测量有轻度创伤性脑损伤 (mTBI) 病史的退伍军人中外泌体和血浆候选血液生物标志物的水平，并检验它们与慢性症状的关系。
使用超敏检测法，在慢性神经创伤后果联盟纵向研究中招募的 195 名退伍军人队列中，测量神经丝轻链（NfL）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-10 和血管内皮生长因子（VEGF）的外泌体和血浆水平。我们检验了候选生物标志物与脑震荡后综合征（PCS）、创伤后应激障碍（PTSD）和抑郁症状之间的关系。比较了无创伤性脑损伤（TBI）（对照组）、1-2 次 mTBI 和重复（3 次或更多）mTBI 之间的生物标志物水平。
外泌体和血浆 NfL 水平升高与重复 mTBI 以及慢性 PCS、PTSD 和抑郁症状相关。血浆 TNF-α水平与 PCS 和 PTSD 症状相关。mTBI 的总次数与外泌体和血浆 NfL 水平以及血浆 IL-6 相关。距最近 TBI 的年数增加与外泌体 NfL 升高和血浆 IL-6 降低相关，而距首次 TBI 的年数增加与外泌体和血浆 NfL 以及血浆 TNF-α和 VEGF 水平升高相关。
重复 mTBI 与外泌体和血浆 NfL 水平升高相关，即使在这些损伤多年后也是如此，在慢性 PCS、PTSD 和抑郁症状患者中升高最明显。我们的结果提示，mTBI 多年后持续存在的症状可能有神经炎症和轴突破坏的基础，尤其是重复 mTBI。
