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CAREER: Investigating Injury Mechanism and Prevention Strategies of Neonatal Brachial Plexus Palsy

$205,454FY2023ENGNSF

Temple University, Philadelphia PA

Investigators

Abstract

The brachial plexus is a group of nerves traveling from the spinal cord in the neck down to the arm. During childbirth, this group of nerves can be injured by mechanical forces, like stretching and pulling. Such a stretch injury to the brachial plexus is called neonatal brachial plexus palsy and can result in varying degrees of paralysis. Though neonatal brachial plexus palsy can be quite detrimental to mobility, there is little data describing how stretching neonatal tissue contributes to injury or how to prevent it, particularly while under the oxygen-starved conditions associated with difficult births. This study will define injury thresholds, i.e., the point at which the tissue structure is irreparably changed by stretching, using animal models. The tissue property data will be used to develop a computational model capable of predicting human-like injury thresholds, which can be used to advance the science of obstetrical care through training and education. The study will test hypotheses relating anatomical location, structural composition, and magnitude of forces exerted on the tissue to the effects on tissue failure and rate of recovery. Research and education are integrated through undergraduate and graduate laboratory-based research, development of a new graduate-level course on integration of biomedical engineering with clinical need, and promoting biomedical engineering in underserved schools of the Philadelphia region with hands-on activities. Dr. Singh's long-term career goal is to minimize the occurrence of neonatal brachial plexus palsy by providing a detailed understanding of the injury mechanism and to develop prevention and treatment strategies based on fundamental knowledge. Toward this goal, Dr. Singh's research objectives are to: (1) provide a detailed understanding of the biomechanical, physiological, and histological properties of both the normal and hypoxic neonatal brachial plexus in neonatal piglets; and (2) utilize the animal model data to train a computational model to investigate the effects of the birth process on the brachial plexus. Specific hypotheses that will be tested include: (1) neonatal brachial plexus tissue will fail at the root/trunk segment; (2) tissue strain rate corresponds to rate of injury recovery; and (3) the extent of stretch directly affects histological outcome. In vivo biomechanical testing will be conducted using large animal surrogates. Experiments will evaluate the effects of stretch and strain using high-speed cameras, neurophysiological recordings, and histological assessments. The computational model development, starting from an existing framework, will focus on incorporating the parameters for neonatal brachial plexus mechanical properties. The insights gained from these studies will bridge a current knowledge gap, connecting the functional response of the neonatal brachial plexus with injury threshold for permanent damage. The research will culminate with a promising clinical translational tool aimed at reducing the prevalence of human injury at birth. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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