Cardali S, Maugeri R
Department of Neurosciences, Psychiatry and Anesthesiological Sciences, University of Messina, Messina, Italy.
J Neurosurg Sci. 2006 Jun;50(2):25-31.
alphaII-Spectrin is the major structural component of the cortical membrane cytoskeleton. It is a major substrate for the calpain and caspase-3 cysteine proteases there are considerable evidence that alfaII-spectrin is processed by the calpains and caspase-3 to signature cleavage products in vivo after experimental traumatic brain injury (TBI). We sought to determine whether aII-spectrin proteolysis is a potentially reliable biomarker for TBI in humans measuring the levels of spectrin and spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI, and studying the relationship between these levels and clinical outcome.
This prospective case control study enrolled 8 patients with severe TBI, defined by a Glasgow Coma Score (GCS) of <8, and requiring intraventricular pressure monitoring. Patients without TBI requiring CSF drainage served as controls. Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 h following TBI and measured for spectrin and SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury.
CSF alphaII-spectrin and calpain and caspase-3 mediated SBDP levels were significantly increased compared to control patients at all time points examined (P<0.001). In patients with a better outcome, CSF spectrin and SBDPs significantly decreased from 6 to 96 h. Patients whose spectrin and SBDP levels remained elevated or failed to decline had a worse outcome (P<0.019).
The present work provides the first evidence that protein degradation of alphaII-spectrin is a reliable marker of severe TBI in humans and that both necrotic and apoptotic cell death mechanisms are activated in humans following a severe TBI. Moreover, the temporal profile of degradation may be an important indicator of clinical outcome.
αII-血影蛋白是皮质膜细胞骨架的主要结构成分。它是钙蛋白酶和半胱天冬酶-3半胱氨酸蛋白酶的主要底物，有大量证据表明，实验性创伤性脑损伤（TBI）后，αII-血影蛋白在体内被钙蛋白酶和半胱天冬酶-3加工成特征性裂解产物。我们试图通过测量重度TBI成年患者脑脊液（CSF）中血影蛋白和血影蛋白降解产物（SBDPs）的水平，并研究这些水平与临床结局之间的关系，来确定αII-血影蛋白的蛋白水解是否是人类TBI的一个潜在可靠生物标志物。
这项前瞻性病例对照研究纳入了8例重度TBI患者，其定义为格拉斯哥昏迷评分（GCS）<8，且需要进行脑室内压力监测。无TBI但需要脑脊液引流的患者作为对照。在TBI后的6、12、24、48、72和96小时从每位患者引流脑室CSF，并测量血影蛋白和SBDPs。在受伤6个月后使用格拉斯哥结局评分（GOS）评估结局。
在所有检查的时间点，与对照患者相比，CSF中αII-血影蛋白以及钙蛋白酶和半胱天冬酶-3介导的SBDP水平均显著升高（P<0.001）。结局较好的患者，CSF血影蛋白和SBDPs从6小时到96小时显著降低。血影蛋白和SBDP水平持续升高或未下降的患者结局较差（P<0.019）。
目前的研究提供了首个证据，即αII-血影蛋白的蛋白质降解是人类重度TBI的可靠标志物，并且在重度TBI后，坏死和凋亡细胞死亡机制在人类中均被激活。此外，降解的时间特征可能是临床结局的重要指标。
