(Dr. Robert S. Cargill III, advisor)

"System to Compress While Electrically Stimulating Hippocampal Brain Slices (SCWESH): Design, Development, and Electromechanical Validation"

Abstract

Traumatic Brain Injury (TBI) imposes a heavy toll on society.  While there is no way to itemize the human losses accompanying the 206,000 hospitalizations, 51,000 deaths, and 80 to 90,000 permanent disabilities that occur annually due to TBI, the tangible cost associated with rehabilitation and lost productivity has a staggering $37 billion impact on the American economy. The Slice Trauma Model for the study of Traumatic Axonal Injury (STM) and the System to Compress While Electrically Stimulating the Hippocampus (SCWESH) are introduced in this thesis to provide a new paradigm for the biomechanical investigation of TBI.

The STM is an in vitro model of the sequence of events leading up to clinically observed traumatic concussion and coma in impulsive, angular, closed-head injuries. Built upon existing studies that describe the deformation of the brain resulting from this injury mode, and the subsequent structural and functional impairments in isolated neurons, the STM (experimental protocol) and SCWESH (experimental system) are designed to investigate functional impairments of a living neural network under similar traumatic conditions. STM protocol examines changes in intercellular communication between live neurons in a slice of rat hippocampal brain tissue as a result of applied compression.  In fulfillment of the STM design criteria, SCWESH uses an electromagnetic linear actuator controlled by a custom Proportional-Integral-Differential (PID) controller to compress a 400?m-thick rat hippocampal brain slice.  Driven by a step function generator, a single compression between 100 and 300?m will be applied, with a rise time between 10 and 50 ms. A tissue chamber with unique perfusion characteristics was designed to maximize the experimental life of the tissue sample. During compression, the brain slice rests on a planar microelectrode array within the tissue chamber, immersed in artificial cerebro-spinal fluid (ACSF).  The slice will be electrically stimulated and excitatory post-synaptic field potential recordings will be taken before and after compression of the tissue to determine changes in the magnitude, conduction velocity, and waveform of action potentials. These changes, when compared with histological studies, will quantify trauma-induced functional impairments in the healthy brain slice, thus providing a path toward new pharmaceutical, clinical, and preventive reductions in the incidence of TBI.