Head Injury Biomechanics Laboratory

Department of Neurological Surgery

Principal Investigators

Kenneth L. Monson, Ph.D.

Current Laboratory Members

David Powell, Ph.D. (Postdoctoral Scholar since September, 2007)

 

Recent Laboratory Members

• Joshua Smith, Ph.D. (now at Lafayette College, Easton, PA)
• Michael Almli (now at the University of Arizona)
• Kirby Chiang, B.S. (now at the University of California, Los Angeles)

 

Laboratory Mission Statement

The overall goal of our work is to improve prevention and treatment of traumatic brain injury by defining injury mechanisms of the cerebral vasculature.

General overview

Nearly all fatal cases of traumatic brain injury (TBI) involve damage to the cerebral vessels, but the mechanisms responsible for these injuries are not well understood. Similarly, little is known about the relationship between traumatic mechanical loading and the cerebrovascular dysfunction that invariably accompanies head trauma. Because of changes associated with development and aging, it is important that these questions be investigated across pediatric, young adult, and elderly age groups.

Areas of Focus

Vascular Interactions During TBI

Building on research from our group characterizing the uniaxial mechanical properties of cerebral vessels, we are working to define mechanical interactions between the vasculature and surrounding brain tissues. This research is being accomplished through four objectives, the first two of which are the delineation of the multi-axial behavior of the cerebral vessels and the description of the relative response and susceptibility of branch regions. Healthy vessels obtained from temporal lobectomy surgeries are subjected to various combinations of axial stretch and pressure in vitro to define their characteristics. Properties of vessels with complex branched geometries are being derived through inverse finite element reconstructions of experiments. Given the close association of the cerebral vessels on the surface of the cortex with the pia and arachnoid membranes, a third area of focus is the characterization of the mechanical response of the pia-arachnoid complex. Pia-arachnoid material resected with blood vessels during temporal lobectomies are similarly being tested in vitro to obtain their properties. The fourth objective in this area focuses on definition of the interactions between vessels and surrounding cranial tissues. These issues are being addressed through both physical and computational models.

 

Traumatic Cerebrovascular Mechanotransduction

In conjunction with efforts to describe the mechanical response of the cerebral vessels, we are also investigating traumatic mechanotransduction phenomena in these vessels in order to better understand the development of secondary injury and pathophysiology. Our work in this area is currently focused on relationships between mechanical loading and matrix metalloproteinase (MMP) activity. The first objective of the research is to define the temporal and spatial expression of MMPs in isolated normal human and mouse cerebral vessels subjected to various levels of traumatic axial stretch ex vivo. Findings from the isolated vessel model will be compared to MMP measurements collected following controlled cortical impact (CCI) in the normal mouse. Finally, wildtype and MMP-null mice will be subjected to CCI, and cerebrovascular permeability and MMP activity will be immuno-localized and compared with finite element model predictions of mechanical stretch in order to test the hypothesis that mechanical stretch induces breakdown of the blood-brain barrier through activation of MMPs.

Funding and Contributors

• National Institutes of Health (National Institute for Child Health and Human Development): Vascular Mechanotransduction in TBI
• Centers for Disease Control and Prevention (National Center for Injury Prevention and Control): Vascular Biomechanics in Traumatic Brain Injury

Collaborators

UCSF Dept. of Neurological Surgery: Geoffrey Manley, M.D., Ph.D.; Nicholas Barbaro, M.D.

UCSF Dept. of Anesthesiology, Center for Cerebrovascular Research: Tomoki Hashimoto, M.D.; William Young, M.D.

UCSF Dept. of Surgery: Nancy Boudreau, Ph.D.

Applied Biomechanics, Inc (Alameda, CA): Louis Cheng, Ph.D.

Wayne State University Department of Biomedical Engineering: Albert King, Ph.D.; King Yang, Ph.D.

Selected Publications

Goldsmith, W., Monson, K. L., 2005. On the state of head injury biomechanics – past, present, and future. Part 2: Physical experimentation. Critical Reviews in Biomedical Engineering 33(2):105-207.

Monson, K. L., Goldsmith, W., Barbaro, N. M., Manley, G. T., 2005. Significance of source and size in the mechanical response of human cerebral blood vessels. Journal of Biomechanics 38(4): 737-744.

Monson, K. L., Goldsmith, W., Barbaro, N. M., Manley, G. T., 2003. Axial mechanical properties of fresh human cerebral blood vessels. Journal of Biomechanical Engineering 125(2): 288-294.

Zhang, L., Bae, J., Hardy, W. N., Monson, K. L., Manley, G. T., Goldsmith, W., Yang, K. H., King, A. I., 2002. Computational study of the contribution of the vasculature on the dynamic response of the brain. Stapp Car Crash Journal 46: 145-163.

Monson, K. L., Goldsmith, W., Barbaro, N. M., Manley, G., 2000. Static and dynamic mechanical and failure properties of human cerebral vessels. In: Crashworthiness, Occupant Protection, and Biomechanics in Transportation Systems 2000, ASME. Ed. by H. F. Mahmood, S. D. Barbat, and M. R. Baccouche. AMD v. 246 / BED v. 49: 255-265.

 

Content provided by UCSF Brain & Spinal Injury Center
Last updated January 29, 2009 10:40 AM

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