Marklund Niklas, Blennow Kaj, Zetterberg Henrik, Ronne-Engström Elisabeth, Enblad Per, Hillered Lars
Department of Neuroscience, Neurosurgery, Uppsala University Hospital, Uppsala, Gothenburg, Sweden.
J Neurosurg. 2009 Jun;110(6):1227-37. doi: 10.3171/2008.9.JNS08584.
Damage to axons contributes to postinjury disabilities and is commonly observed following traumatic brain injury (TBI). Traumatic brain injury is an important environmental risk factor for the development of Alzheimer disease (AD). In the present feasibility study, the aim was to use intracerebral microdialysis catheters with a high molecular cutoff membrane (100 kD) to harvest interstitial total tau (T-tau) and amyloid beta 1-42 (Abeta42) proteins, which are important biomarkers for axonal injury and for AD, following moderate-to-severe TBI.
Eight patients (5 men and 3 women) were included in the study; 5 of the patients had a focal/mixed TBI and 3 had a diffuse axonal injury (DAI). Following the bedside analysis of the routinely measured energy metabolic markers (that is, glucose, lactate/pyruvate ratio, glycerol, and glutamate), the remaining dialysate was pooled and two 12-hour samples per day were used to analyze T-tau and Abeta42 by enzyme-linked immunosorbent assay from Day 1 up to 8 days postinjury.
The results show high levels of interstitial T-tau and Abeta42 postinjury. Patients with a predominantly focal lesion had higher interstitial T-tau levels than in the DAI group from Days 1 to 3 postinjury (p < 0.05). In contrast, patients with DAI had consistently higher Abeta42 levels when compared with patients with focal injury.
These results suggest that monitoring of interstitial T-tau and Abeta42 by using microdialysis may be an important tool when evaluating the presence and role of axonal injury following TBI.
轴突损伤会导致受伤后残疾，在创伤性脑损伤（TBI）后很常见。创伤性脑损伤是阿尔茨海默病（AD）发生的一个重要环境风险因素。在本可行性研究中，目的是使用具有高分子截留膜（100 kD）的脑内微透析导管，在中重度创伤性脑损伤后收集间质总tau蛋白（T-tau）和淀粉样β蛋白1-42（Aβ42），它们是轴突损伤和阿尔茨海默病的重要生物标志物。
8名患者（5名男性和3名女性）纳入研究；其中5名患者为局灶性/混合性创伤性脑损伤，3名患者为弥漫性轴突损伤（DAI）。在对常规测量的能量代谢标志物（即葡萄糖、乳酸/丙酮酸比值、甘油和谷氨酸）进行床边分析后，将剩余的透析液合并，从受伤后第1天到第8天，每天取两个12小时的样本，通过酶联免疫吸附测定法分析T-tau和Aβ42。
结果显示受伤后间质T-tau和Aβ42水平较高。在受伤后第1天至第3天，以局灶性病变为主的患者间质T-tau水平高于弥漫性轴突损伤组（p<0.05）。相比之下，弥漫性轴突损伤患者的Aβ42水平始终高于局灶性损伤患者。
这些结果表明，在评估创伤性脑损伤后轴突损伤的存在和作用时，使用微透析监测间质T-tau和Aβ42可能是一个重要工具。
