Temporal Lobe Epilepsy, Stroke, and Traumatic Brain Injury: Mechanisms of Hyperpolarized, Depolarized, and Flow-Through Ion Channels Utilized as Tri-Coordinate Biomarkers of Electrophysiologic Dysfunction.

ABSTRACT

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.