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

Apply to join the Cullen Lab

CBIR Logo

Neurosurgery

News and Events

  • The Cullen Lab's research in TBI was featured in the Fall issue of Penn Medicine Magazine (p. 15-17). PDF
  • Dr. Cullen and colleague Dr. Douglas Smith were awarded a 3-year grant from the Department of Defense Joint Warfighter Medical Research Program to advance their work for "Repair of Segmental Nerve Defects Using Tissue-Engineered Nerve Grafts."
  • Dr. Cullen was invited to give a research talk at the Center for Translational Injury Research at the University of Texas Health Science Center in Houston, TX. He presented “Tissue Engineered Nerve Grafts for Peripheral and Central Nervous System Repair”.
  • The Cullen Lab was awarded a one-year pilot grant through the Penn Medicine Neuroscience Center to explore "Neuromodulation of Brain Circuits Using Transplantable Micro-Tissue Engineered Neural Networks."
  • James Harris, Ph.D., was awarded an NIH NRSA Postdoctoral Fellowship on the "Brain Injury Training Grant" through Penn's Center for Brain Injury & Repair. Dr. Harris' project is on "Mechanisms of Biophysical Responses and Neurodegeneration following Concomitant Blast and Inertial Traumatic Brain Injury."
  • Dr. Cullen gave a lecture at the American Society for Peripheral Nerve Annual Meeting in Kauai, Hawaii in January. The talk was titled "Tissue Engineered Grafts Accelerate Peripheral Nerve Repair By Direct Axon-Induced Axon Regeneration."
  • Laura Struzyna was a Poster Award Finalist at the Tissue Engineering and Regenerative Medicine International Society Annual Meeting in Atlanta, Georgia in November. Her poster was titled "Tissue Engineered Grafts Accelerate Peripheral Nerve Repair By Direct Axon-Induced Axon Regeneration."
  • Dr. Cullen gave an Invited Lecture at the Department of Biomedical Engineering at the Georgia Institute of Technology in May. He presented "Tissue Engineering Strategies to Restore Neural Circuitry and Create Living Scaffolds for Targeted Axonal Regeneration."
  • Dr. Cullen and collaborator Dr. Douglas Smith were awarded funding from the Department of Defense through the Rutgers - Cleveland Clinic Consortium of the Armed Forces Inst. of Regenerative Medicine. This project will investigate the efficacy of novel tissue engineered constructs encased in custom-built nerve guidance tubes to promote nerve regeneration following major peripheral nerve injury.
  • Bioengineering Ph.D. Candidate, Laura Struzyna, was selected for a prestigious 3-year Graduate Research Fellowship through the National Science Foundation based on her proposal for "Tissue Engineered Constructs for Neural Regeneration."

View more news. →