Hydrocephalus, an imbalance between cerebrospinal fluid production and absorption, is diagnosed in more than 1 in 500 people in the United States. Approximately 80% of these patients will suffer long-term neurological deficits. Genetic diseases, meningitis, subarachnoid hemorrhage, stroke, traumatic brain injury, or tumors cause hydrocephalus. The common treatment for all hydrocephalus patients is CSF drainage by shunting. Despite all our efforts, shunts still have the highest failure rate of any neurological device. A shocking 98% of shunts fail after just ten years, a rate bumped up by the 80% of patients who suffer from tens if not hundreds of repetitive shunt failures. Shunts fail after becoming obstructed with attaching glia, creating a substrate for more glia or other cells and tissues (e.g. choroid plexus) to secondarily bind and block the flow of CSF through the shunt. Since glial attachment is a primary mechanism for shunt failure, we need to find out what it is about the pathophysiology of hydrocephalus that cause glia to attach and cause repetitive shunt failure. Until these cues are identified, we cannot address shunt failure in a principled way. In our first approach, we correlate patient revision history to change in cell attachment, hypothesizing that shunt failure exacerbates the likelihood for repeat shunt failure. In our second approach, we probe the mechanisms of shunt failure due to ever-present glia, specifically, how glial attachment changes as a function of factors influenced by repeat shunt failure. In our third approach, we probe mechanisms of shunt failure by blocking factors influenced by repeat shunt failure, and in doing so, propose methods to mitigate perpetual shunt failure. Methods include a first application of high-throughput, high-resolution, multi-spectral imaging and use of the FARSIGHT toolkit to provide a comprehensive quantitative analysis of the interaction between glia and the shunt. This project will set the stage for specific cause-effect engineering hypotheses to improve shunt design and ultimately lead to a fundamental leap of knowledge in hydrocephalus treatment. It will provide the foundation for my independent career managing a successful bioengineering research laboratory improving neuroprosthetics using biologically inspired design principles while providing professional development opportunities that allow me to train with the fields leading experts.

Public Health Relevance

Hydrocephalus is a disorder causing excess accumulation of cerebrospinal fluid in the brain, treated by using shunts to divert cerebrospinal fluid out of the cranial cavity. Nearly all shunts fail requiring patients to undergo several if not hundreds of shunt revisions in their lifetime. In this project, our team of neuroengineers, neurosurgeons, a pathophysiologist, a pathologist, and two experts in quantitative image analysis will identify if a patient's shunt failure history modifies glial attachment and causes higher rates of subsequent shunt failure. By studying correlations in the patient population and causations using an in vitro model, we embrace a multi- disciplinary approach that will provide a better understanding of an important biomedical problem in order to improve technology and patient outcome.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section (BNVT)
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Aguel, Felipe
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Wayne State University
Schools of Medicine
United States
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Garling, Richard Justin; Sood, Sandeep; Harris, Carolyn Anne (2017) Avoiding the pocket: A case report of coiling of distal shunt catheter into subcutaneous pocket. Int J Surg Case Rep 41:61-64
Hanak, Brian W; Bonow, Robert H; Harris, Carolyn A et al. (2017) Cerebrospinal Fluid Shunting Complications in Children. Pediatr Neurosurg 52:381-400
Hanak, Brian W; Ross, Emily F; Harris, Carolyn A et al. (2016) Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices. J Neurosurg Pediatr 18:213-23