Hofstetter
Laboratory
University of Washington
Department of Neurological Surgery
OUR RESEARCH
Our laboratory focuses on the spinal cord. In particular, we target systems of the spinal cord that may have a direct positive impact on patient care at the University of Washington Medical Center. We have a variety of ongoing projects.
CUTTING EDGE TECHNOLOGIES FOR REAL TIME SPINAL BLOOD FLOW MONITORING
In collaboration with Dr. Matthew Bruce at UW's Applied Physics Laboratory, we are implementing a novel Ultrafast Contrast-Enhanced Ultrasound platform to monitor hemodynamic changes after spinal cord injury with unprecedented temporal and spatial resolution. By combining a contrast agent with high frequency plane-wave ultrasound imaging, we are able to visualize tissue perfusion, as well as changes in vessel architecture and blood flow velocities. We believe that this technology will lead to significant improvements in the ability of physicians to identify tissue at risk for secondary damage after injury. Eventually this technology might lead to better functional outcomes for patients with acute spinal cord injury.
INTERVENTIONS TO HALT ACUTE HEMORRHAGE AFTER TRAUMA
Spinal cord injury can lead to a near complete loss of blood flow at the site of injury, along with significant reductions in blood flow in adjacent tissue. This loss of blood flow is a key contributor to the secondary phase of injury, characterized by tissue swelling, inflammation, and progressive cell death. Therapies that can prevent hemorrhage after injury may be instrumental in limiting the extent of secondary spinal cord damage.
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Our lab is currently attempting to reduce spinal blood loss with the administration of hemostatic nanoparticles, produced in the lab of Dr. Erin Lavik at the University of Maryland. In an attempt to limit postoperative hemorrhage, rodents are treated with intravenous nanoparticles (green). Particles are seen in the lesion area of an acutely injured spinal cord. The blood vessels are depicted in red.
UNDERSTANDING THE ROLE OF THE IMMUNE SYSTEM IN ACUTE SPINAL CORD INJURY
After spinal cord injury, the resulting tissue damage and reduced blood flow leads to the activation and recruitment of immune cells. Throughout the main cavity of necrotic spinal tissue, the activity of resident microglia and invading macrophages lead to axon degeneration. Astrocytes surround and encase the cavity, which serves as a barrier to axon regeneration. The inflammatory immune response following spinal cord injury plays a key role in the expansion of the initial area of tissue necrosis.
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Currently, we are engaged in studies aimed at altering the inflammatory response to spinal cord injury by targeting macrophages, promoting the formation of anti-inflammatory phenotypes over pro-inflammatory ones. We are also investigating the specific role that extracellular matrix degradation plays in initiating the inflammatory response.
STRATEGIES TO RESTORE BLADDER FUNCTION AFTER SPINAL CORD INJURY
More than 80% of all patients with spinal cord injury suffer from neurogenic bladder. Commonly, spinal cord injury causes an imbalance in the signals to the bladder that regulate contraction and relaxation, which leads to elevated bladder pressures and damage to the bladder's muscles. Aside from significantly impairing quality of life, neurogenic bladder can lead to an elevated risk for numerous other urinary tract disorders.
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A common treatment strategy for neurogenic bladder is to denervate the detrusor muscle, which is responsible for contraction during urination. This has been shown to reduce bladder pressures and improve bladder compliance in patients. However, in many cases this treatment is applied after significant damage to the bladder has already occurred. Our lab is currently investigating the efficacy of performing bladder denervation acutely after spinal cord injury. Findings from these studies may pave the way for improved clinical bladder management strategies.
