Blast-Induced Traumatic Brain Injury

Blast exposure is a 21st century reality in counter-insurgency warfare. The high incidence of closed head non-impact blast-induced traumatic brain injury (bTBI) in warfighters serving in Iraq and Afghanistan suggests a direct mechanism by which blast exposure detrimentally affects the brain. However, potentially unique injury mechanisms and exposure thresholds for bTBI remain unknown. The Cullen Lab is working to identify acute biophysical responses of neural cells occurring directly due to blast wave propagation through the brain. Relating these patterns of sub-cellular damage to both the predicted micro-injury biomechanics and later, evolving neuropathology may permit establishment of a “signature” of bTBI.

Neural Cellular Biophysical Responses to Blast Exposure

Damaged Neurons

caption: Blast-induced cellular damage (yellow) in the rat hippocampus

Movie

Damaged neurons (green) in the rat cortex following blast

Degenerating cortical neurons following blast exposure

caption: Degenerating neurons in the rat cortex following blast

Colorimetric Materials-Based Dosimetry Using Photonic Nanocrystals

To compliment these efforts, we have developed a novel materials-based blast injury dosimeter using photonic crystalline nanostructures that change color specifically following blast exposure. Appearing as an array of small colored stickers, these nanostructures may be affixed to uniforms and helmets to report blast exposure sufficient to induce even subtle neuropathology. Our current efforts focus on calibrating the degree of color change and/or color loss with blast levels inducing brain injury across a range of severities. This technology offers a lightweight, power-free sensor that can be readily interpreted by the naked eye, thus serving as an experimental tool as well as a diagnostics marker to improve bTBI outcomes in our warfighters. Collectively, our efforts to elucidate the causative mechanism(s) and potentially unique neuropathology of bTBI in parallel with blast dosimetry help establish exposure tolerances and facilitate the development of treatments to halt progressive neural damage and/or degeneration.

Colorimetric blast

BID concept and function

(A) BID arrays may be affixed to warfighter uniforms in multiple locations. These arrays consist of multiple engineered photonic crystalline microstructures, the colorimetric properties of which are a result of the nano-scale structure, creating so-called “structural color”. (B) We have previously demonstrated that blast exposure precisely disrupts the structure at the nano- and micro-scales, creating color change and loss, respectively (color change/loss scale bar: 1 mm; SEM scale bar: 500 nm). These properties make our photonic crystalline arrays ideal to serve as a colorimetric blast injury dosimeter.

Contact Information

D. Kacy Cullen, Ph.D
105E Hayden Hall, 3320 Smith Walk
Philadelphia, PA 19104
dkacy@mail.med.upenn.edu

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News and Events

  • Dr. Cullen and colleagues Dr. John Duda and Dr. John Wolf received a 5-year Merit Review from the Department of Veterans Affairs entitled "Chronic Neurodegenerative and Neurophysiological Sequela of Closed-Head TBI."
  • Dr. Cullen and Dr. Smith have an article published in Scientific American titled "Bionic Connections" describing their efforts to develop biohybrid neuroprosthetic interfaces (http://www.scientificamerican.com/article.cfm?id=how-artifical-arms-could-connect-nervous-system). In addition, the magazine published a web-based companion article on the use of this neural tissue engineering technology to repair peripheral nerve injuries (http://scientificamerican.com/article.cfm?id=bionic-limb-researchers-build-new-bridges-nerve-injury).
  • Dr. Wolf and Laura Struzyna gave nanosymposium presentations at the Society for Neuroscience conference in New Orleans, LA. Dr. Wolf presented "Alterations in Hippocampal Circuitry Post Diffuse Brain Injury in a Swine TBI Model". Laura Struzyna presented "A Stragey for Functional Restoration of Brain Pathways Using Micro-Tissue Engineered Constructs Containing Living Axon Tracts".
  • Dr. Cullen gave a lecture at the Military Health System Research Symposium (MHSRS) in Ft. Lauderdale, FL detailing his recent work in "Acute Biophysical Responses and Neurophysiological Sequelae following Closed-Head Traumatic Brain Injury in Swine".
  • Commentary by Dr. Cullen was featured in a blog post about brain-based neural electrical interface systems: innovation-how-a-paralyzed-peson-uses-thoughts-to-control-a-robotic-arm
  • Dr. Cullen was interviewed for a blog post regarding the effects of traumatic brain injury on NFL athletes: http://physicsbuzz.physicscentral.com/2012/05/physics-of-hit-football-concussions.html
  • The Cullen Lab was awarded a grant from Axonia Medical, Inc. to advance novel neural tissue engineering technology to improve neuroregeneration following severe peripheral nerve injury.
  • A new company, Cerebid Technologies, has been formed by Dr. Cullen along with Ray Krauss, Douglas Smith and Shu Yang, to focus on translating their unique blast-sensitive photonic nanocrystals. These photonic nanocrystals, which change color following exposure to blast, are being developed as a "Blast Badge" to measure an individual soldiers blast exposure levels relative to thresholds for blast-induced traumatic brain injury, the "signature injury" in warfighters in Iraq and Afghanistan.
  • Dr. Cullen was invited to give a research talk at the Neuroprotection Research Seminar Series through the Shock, Trauma and Anesthesiology Research Center (STAR-ORC) at the University of Maryland School of Medicine, Baltimore, MD. He presented "Closed-Head Blast vs. Inertial TBI: Cellular Biophysical Responses and Neurophysiological Sequela".
  • Dr. Cullen was an Invited Speaker at the 2nd World Congress on Biotechnology in Philadelphia, PA. He presented "Neural Tissue Engineering Strategies for Cell Replacement and Axon Regeneration".

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