Irazuzta J E, de Courten-Myers G, Zemlan F P, Bekkedal M Y, Rossi J
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH, USA.
Brain Res. 2001 Sep 14;913(1):95-105. doi: 10.1016/s0006-8993(01)02764-0.
Brain injury due to bacterial meningitis affects multiple areas of the brain with a heterogeneous distribution generating a challenge to assess severity. Tau proteins are microtubular binding proteins localized in the axonal compartment of neurons. Brain injury releases cleaved Tau proteins (C-tau) into the extracellular space where they are transported to the cerebral spinal fluid. We hypothesized that C-tau crosses the blood-brain barrier during inflammation and that it can be detected in serum. The correlation between serum C-tau levels and the extent of the meningitic insult was examined. Furthermore, we studied whether the use of a subset of neurobehavioral tasks can assess the extent of brain injury after meningitis. The tests were chosen primarily for their ability to detect deficits in the acoustic system, low brain, reflexive responding, as well as for impaired motor coordination and the higher brain functions of learning and memory. A rat model of group B streptococcal meningitis with variable severity was utilized. At five days after bacterial inoculation followed by antibiotic therapy neurobehavioral tests were performed and serum C-tau and histologic samples of the brain were obtained. Our study shows that during meningitis C-tau appears in serum and reflects the extent of neurologic damage. Neurobehavioral performance was altered after bacterial meningitis and could be correlated with histologic and biochemical markers of neurologic sequelae. We conclude that serum C-tau and a composite of neurobehavioral tests could become useful markers for assessing the severity of neurological damage in experimental bacterial meningitis.
细菌性脑膜炎所致脑损伤会影响大脑的多个区域,其分布不均,给评估严重程度带来挑战。 Tau蛋白是定位于神经元轴突区室的微管结合蛋白。脑损伤会将裂解的Tau蛋白(C-tau)释放到细胞外空间,然后被转运至脑脊液中。我们推测C-tau在炎症期间会穿过血脑屏障,并且可以在血清中检测到。我们研究了血清C-tau水平与脑膜炎损伤程度之间的相关性。此外,我们还研究了使用一组神经行为任务能否评估脑膜炎后脑损伤的程度。这些测试主要因其能够检测听觉系统、低位脑、反射性反应方面的缺陷,以及运动协调受损和学习与记忆等高级脑功能方面的缺陷而被选用。我们使用了具有不同严重程度的B组链球菌脑膜炎大鼠模型。在细菌接种并进行抗生素治疗五天后,进行神经行为测试,并采集血清C-tau和脑的组织学样本。我们的研究表明,在脑膜炎期间C-tau会出现在血清中,并反映神经损伤的程度。细菌性脑膜炎后神经行为表现会发生改变,并且与神经后遗症的组织学和生化标志物相关。我们得出结论,血清C-tau和一组神经行为测试可能会成为评估实验性细菌性脑膜炎神经损伤严重程度的有用标志物。