Sizemore Gina, Lucke-Wold Brandon, Rosen Charles, Simpkins James W, Bhatia Sanjay, Sun Dandan
Department of Clinical and Translational Science, West Virginia School of Medicine, Morgantown, WV.
Department of Neurosurgery, West Virginia School of Medicine, Morgantown, WV.
OBM Neurobiol. 2018;2(2). doi: 10.21926/obm.neurobiol.1802009. Epub 2018 Jun 4.
The brain is an integrated network of multiple variables that when compromised create a diseased state. The neuropathology of temporal lobe epilepsy (TLE), stroke, and traumatic brain injury (TBI) demonstrate both similarity and complexity that reflects this integrated variability; TLE with its live human tissue resection provides opportunity for translational science to demonstrate scale equivalent experimentation between the macroscopic world of clinical disease and the microscopic world of basic science. The extended value of this research is that the neuroinflammatory abnormalities that occur throughout astrocytes with hippocampal sclerosis and damaged or even reversed signaling pathways (inhibition to excitation such as with gaba-aminobutyric acid) are similar to those seen in post-stroke and TBI models. In evaluation of the epilepsy population this interconnectedness of pathology warrants further evaluation with collaborative efforts. This review summarizes patterns that could shift experimentation closer to the macro level of humanity, but still represent the micro world of genetics, epigenetics, and neuro-injury across etiologies of physiologic dysfunction such as TLE, stroke, and TBI with evaluation of cell function using electrophysiology. In conclusion we demonstrate the plausibility of electrophysiologic voltage and current measurement of brain tissue by patch clamp analysis to specify actual electrophysiologic function for comparison to electroencephalography in order to aid neurologic evaluation. Finally, we discuss the opportunity with multiscale modeling to display integration of the hyperpolarization cyclic-nucleotide gated channel, the depolarized calcium channels, and sodium-potassium-chloride-one/potassium-chloride-two co-transporter channels as potential mechanisms utilized as tri-coordinate biomarkers with these three forms of neurologic disease at a molecular scale of electrophysiologic pathology.
大脑是一个由多个变量组成的集成网络，当这些变量受到损害时就会产生疾病状态。颞叶癫痫（TLE）、中风和创伤性脑损伤（TBI）的神经病理学表现出既相似又复杂的特点，反映了这种集成的变异性；TLE通过活体人类组织切除，为转化科学提供了机会，以展示临床疾病宏观世界与基础科学微观世界之间的等效规模实验。这项研究的更大价值在于，在海马硬化的星形胶质细胞中出现的神经炎症异常以及受损甚至逆转的信号通路（如γ-氨基丁酸介导的抑制到兴奋）与中风后和TBI模型中所见的相似。在评估癫痫患者群体时，这种病理学的相互关联性值得通过合作努力进行进一步评估。本综述总结了一些模式，这些模式可以使实验更接近人类的宏观层面，但仍能代表遗传学、表观遗传学以及跨生理功能障碍病因（如TLE、中风和TBI）的神经损伤微观世界，并使用电生理学评估细胞功能。总之，我们通过膜片钳分析证明了对脑组织进行电生理电压和电流测量以确定实际电生理功能的合理性，以便与脑电图进行比较，从而辅助神经学评估。最后，我们讨论了多尺度建模的机会，以展示超极化环核苷酸门控通道、去极化钙通道以及钠-钾-氯-1/钾-氯-2共转运通道的整合，作为在电生理病理学分子尺度上与这三种神经疾病相关的潜在机制，用作三坐标生物标志物。
