Date of Award

Fall 2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Bryan J. Pfister

Second Advisor

Vijayalakshmi Santhakumar

Third Advisor

Bruce G. Lyeth

Fourth Advisor

Kevin Pang

Fifth Advisor

Mesut Sahin

Abstract

Traumatic Brain Injury (TBI) is a physical impact to the head resulting in functional deficits in memory and motor systems. TBI is a prevalent problem occurring in 1.7 million people annually in the United States (Faul et al. 2010). TBIs can differ greatly in terms of the biomechanics of the impact such as magnitude, direction and rate. Indeed, it is likely that the wide range of TBI outcomes may be due to the physical characteristics of the trauma. Studies to date on impact have used injury devices with limited alterable parameters. Therefore, the existing impact studies have considered the effect of magnitude of the primary impact and have not addressed issues such as rate of pressure increase that may be important in understanding the differences in pathology associated with these impacts.

In this study a novel modular computer controlled device capable of inducing controlled TBI is designed. To achieve maximum control and sensitivity, a closed loop voice coil control device is utilized, to more accurately and precisely generate the temporal force function delivered by the FPI device. This device enables generation of pressure profiles very similar to the ones generated from conventional FPI devices; in addition, different aspects of the pressure profiles such as the rate can be changed. This unique feature of this device is utilized to study the pathophysiological effects of increasing rates of pressure rise time on the rodent brain.

A series of behavioral studies are conducted including neurological severity tests immediately after the injury followed by rotarod, ladder rung walk, metric and spatial information, and Morris water maze tasks between 1 to 15 days post injury. Also, the perforant path-evoked granule cell field excitability is tested. Histological characterization is performed at 4h, 24 h and 15 days post injury.

The results show that a faster rate injury results in a reduced acute cell loss and improved immediate neurological outcome, but enhanced granule cell field excitability 1- week post injury. Results from immediate and chronic behavioral analysis after the injury; suggests better functional outcome in the fast injuries compared to slower injuries. However, fast injuries show a greater progressive cell loss and similar deficits in spatial information recognition as the slower rate injuries.

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