Thesis (Ph.D.)--Boston University / The widespread use of Improvised Explosive Devices (IEDs) in the Wars in Iraq and Afghanistan has caused a dramatic increase in shockwave-induced mild Traumatic Brain Injury (mTBI), leading mTBI to be dubbed the 'signature injury' of modern warfare. Currently, the pathology of shockwave-induced mTBI is unknown , and it is diagnosis is based on self-reported symptoms and combat history. While the etiological mechanism has not yet been determined , it is becoming increasingly accepted that shockwaves themselves are the brain-damaging agent that emanate from IEDs. To assess how mild, sub-lethal shockwaves might damage brain tissue, we developed an in vitro assay to deliver shockwaves to neuronal cells in culture, and then assayed several properties of these cells that affect their function. This assay involved exposing rat cortical and hippocampal primary neuronal cultures to shockwaves of increasing magnitude generated with a biolistic Gene Gun. The Gene Gun produces shockwaves of sufficient overpressure to cause cognitive impairment in animal models of shockwave-induced mTBI. Our results show that overpressures of ~1.0 pound per square inch (psi) caused transient membrane permeability for molecules up to ~12 nanometers in diameter. This change in membrane permeability was accompanied by a transient decrease in cellular ATP levels and synaptic densities. This synaptic degeneration correlated with changes in the level and phosphorylation state of several synaptic proteins examined. Similar results were observed in dissected rat retinas suggesting that these shockwave-induced effects can occur in complex tissues, such as the brain. Based on these findings we propose that shockwaves damage cellular membranes, leading to a decrease in intracellular ATP, and ultimately to a reduced numbers of synapses, the part of neurons most important for learning, memory and behavior. Additional experiments in whole animals will be required to ascertain whether shockwave-induced cellular damage and synaptic degeneration plays an etiological role in shockwave-induced mTBI.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/31551 |
| Date | January 2012 |
| Creators | Ferenc, Matthew Teague |
| Publisher | Boston University |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | This work is being made available in OpenBU by permission of its author, and is available for research purposes only. All rights are reserved to the author. |
Page generated in 0.0017 seconds