Approximately 1.4 million Americans suffer from traumatic brain injury, and about 250,000 patients require hospitalization per year. However, there is no approved pharmaceutical treatment to ameliorate this type of brain damage due to a lack of understanding of the mechanisms underlying traumatic brain injury. Development of intervention strategies to prevent or minimize posttraumatic damage requires a better understanding of injury mechanisms, response and tolerance levels. This work studied posttraumatic, functional changes of the hippocampus by quantifying electrophysiological alteration after experimental traumatic brain injury.
Electrophysiological function of the immature hippocampus was disrupted after 5%, 10% and 20% deformation. The degree of dysfunction was dependent on the magnitude of the applied strain. The age of the tissue at the time of injury was found to be an important factor affecting posttraumatic, functional outcome with an age-related window of reduced vulnerability to injury. Moreover, the excitability of neural networks in the hippocampal slice cultures increased after 20% deformation, indicating a posttraumatic hyperexcitability. Our results suggested that the posttraumatic attenuation of gamma-aminobutyric acid mediated inhibition and deficiency of glutamate receptor subunit-2 editing, indicated by the up-regulation of Na-K-2C1 cotransporter-1 and Q-type glutamate receptor subunit-2 after injury, may contribute to the hyperexcitability.
Traumatic brain injury results in brain dysfunction caused by a mechanical stimulus, thus a research platform which can quantitatively combine mechanical inputs with functional outcomes will be helpful in elucidating traumatic brain injury pathology. We developed stretchable microelectrode arrays, which were incorporated with our established in vitro injury model to enable electrophysiological recording before and after injury. By precisely controlling mechanical injury parameters, specific levels of damage quantified by functional outcomes can be generated, and the effect of mechanical stimuli on neuron function can be studied.
To develop a novel traumatic brain injury research platform for dual-mode recording of neuroelectrical and neurochemical activity, we demonstrated the use of vertically aligned carbon nanofiber arrays for both stimulating and monitoring electrophysiological signals from hippocampal slice cultures. This novel technology will make possible the simultaneous recording of electrophysiology and neurotransmitter concentration. Recording electrophysiology with the vertically aligned carbon nanofiber arrays was an important step toward that goal.