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Principal Investigator: Anita Singh
Organization: TEMPLE UNIV OF THE COMMONWEALTH
Fiscal Year: 2024
Award: $347,348
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Neonatal Brachial Plexus Palsy (NBPP) is a complication of childbirth that can result in significant long-term
sequelae. NBPP associated injuries often include cases of spinal cord injury (SCI) and are very poorly
understood. Our long-term research goals are to develop both prevention and treatment strategies for NBPP.
Consequently, objectives of this study are to use our novel and unique clinically-relevant neonatal piglet model:
a) To identify brachial plexus (BP) strains and forces that lead to morphological and functional SCI by
investigating the effects of BP stretch on acute pathology and functionality within the spinal cord (SC), b) To
investigate clinically-relevant systemic biomarkers for early diagnosis of SCI during NBPP, and c) To develop
computational models of maternal pelvis and fetus that predict risk of NBPP and associated SCI during
complicated NBPP delivery scenarios. Based on our preliminary work, our central hypothesis is that moderate
to severe BP stretches will transmit forces to SC resulting in SC tissue damage, which are also observable as
high expression of systemic injury biomarkers in the serum and cerebrospinal fluid, and suppression or loss of
motor neuron excitability. Our innovative approach is aimed at developing new knowledge of acute NBPP injury
mechanisms and report SCI tolerance values of BP strains and forces. These data will enable novel clinical tools
for diagnosis and prevention, as well as suggest targets for early clinical interventions for NBPP. We will test the
overall hypothesis through the following independent specific aims: 1) To determine whether moderate to
severe BP stretches will lead to SCI as evident by acute SCI markers in situ, functional loss in motor
neurons and systemic acute SCI biomarkers, and 2) To identify delivery maneuvers and NBPP risk
factors that lead to abnormal BP strains and forces, increasing the likelihood of associated SCI. The
expected outcomes of this work are the first ever data on: 1) morphological and functional injury outcomes that
help determine SCI tolerance values of BP strains and forces during BP stretch, 2) molecular biomarkers that
can enable early diagnosis of SCI, and 3) developing highly biofidelic computational models for NBPP prediction
and obstetric training. The results will also have an important positive impact, because, they lay the groundwork
to develop a new class of targeted clinical interventions.
Terms: <3-D><3-Dimensional><3D><Acute><Animals><Area><Assay><Bioassay><Biochemical><Biological Assay><Biological Markers><Biomechanics><Bleeding><Blood Serum><Body Tissues><Brachial Plexus><Brachial plexus structure><Cadaver><Cerebrospinal Fluid><Childbirth><Clinical><Complex><Complication><Computer Models><Computerized Models><Data><Development><Devices><Diagnosis><Diagnostic><Discipline of obstetrics><Dysfunction><Early Diagnosis><Early Intervention><Early treatment><Electrophysiology><Electrophysiology (science)><Elements><Event><Failure><Fetus><Functional disorder><Fusimotor Neurons><Gamma Motor Neurons><Gamma-Efferent Motor Neurons><Goals><Head and Neck><Head and neck structure><Hemorrhage><Histologic><Histologically><Human><In Situ><Inflammatory Response><Injury><Intervention><Intervention Strategies><Knowledge><Lateral><Lead><Lifelong disability><Maps><Medulla Spinalis><Modeling><Modern Man><Molecular><Morphology><Motor Cell><Motor Neurons><NIH><National Institutes of Health><Neonatal><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Obstetrics><Outcome><Palsy><Paralysed><Pathologic><Pathology><Pb element><Pelvic><Pelvic Region><Pelvis><Permanent disability><Physiopathology><Plegia><Predicting Risk><Preventative strategy><Prevention><Prevention strategy><Preventive strategy><Primiparity><Property><Proteomics><Publishing><Reporting><Research><Research Priority><Risk><Risk Factors><Science><Serum><Spinal><Spinal Cord><Spinal Cord Trauma><Spinal Trauma><Spinal cord injured><Spinal cord injury><Stretching><Testing><Therapeutic><Tissues><Training><Transmission><Traumatic Myelopathy><United States National Institutes of Health><Visualization software><Work><avulsion injury><bio-markers><biochemical model><biologic marker><biomarker><biomechanical><birth complications><blood loss><cadaveric><cadavers><cerebral spinal fluid><child birth><clinical development><clinical diagnostics><clinical relevance><clinical training><clinically relevant><combinatorial><computational modeling><computational models><computer based models><computer based prediction><computerized modeling><critical injury><delivery complications><devastating injury><developmental><diagnostic tool><early biomarkers><early detection><early detection biomarkers><early detection markers><early therapy><electrophysiological><fetal><force sensor><forecasting risk><functional loss><functional status><heavy metal Pb><heavy metal lead><in silico><in vivo><injuries><injury prevention><innovate><innovation><innovative><insight><interventional strategy><long-term sequelae><medical diagnostic><molecular biomarker><molecular marker><motoneuron><motor neuron degeneration><neonatal care><neural inflammation><neuroinflammation><neuroinflammatory><neuronal><neuronal excitability><next generation><novel><paralysis><paralytic><pathophysiology><pig model><piglet model><porcine model><predict risk><predict risks><predicted risk><predicted risks><predicting risks><predictive modeling><predictive risk><predictive tools><predicts risk><pressure><prevent><preventing><primipara><response><risk prediction><risk predictions><severe injury><simulation><spinal fluid><swine model><three dimensional><tool><transmission process><treatment strategy><visualization tool><γ Motor Neurons>