Biomarkers for Recovery of Veterans with Severe Spinal Cord Injury

Accurate prognosis prediction is essential for planning rehabilitation programs and setting functional goals of veterans with spinal cord injury (SCI). A gap in our knowledge is how to identify veterans with SCI with greater potential to recover early after injury. The overall goal of this proposal is to examine the potential of physiological and blood-based biomarkers to predict neurological and functional recovery in veterans with motor complete and incomplete SCI during inpatient rehabilitation. To address this question, we propose to implement a multisite clinical trial that will involve for VA sites: Edward Hines Jr. VA Hospital (leading site), Louis Stokes Cleveland VA Medical Center, James A. Haley Veterans' Hospital, and West Roxbury VA Medical Center to assure geographic and socio-demographic variation, and successful recruitment goals. In Aim 1, we will investigate the relationship between spasticity and neurological and functional recovery in veterans with SCI. A relationship has been found between residual corticospinal connectivity and severity of spasticity following SCI. We propose to measure spasticity in muscles below the level of injury bilaterally in veterans with SCI using clinical and kinematic outcomes at admission to and discharge from inpatient rehabilitation. Neurological recovery will be assessed by the International Standards for Neurological Classification of Spinal Cord Injury exam and functional recovery will be assessed by the Functional Independence Measure exam and quality of life outcomes. In Aim 2, we propose to determine the relationship between blood-based biomarkers and neurological and functional recovery in veterans with SCI. Brain-derived neurotrophic factor (BDNF) and single-nucleotide polymorphisms in BDNF play a critical role in promoting neuronal plasticity. We propose to measure serum levels of BDNF by using enzyme-linked immunosorbent assays (ELISA) at admission to and discharge from inpatient rehabilitation. The proposed experiments will provide new knowledge that could help to identify sensitive and easy-to-use biomarkers to predict recovery in veterans with SCI and affect the standard of care in the VA health care medical system. The absence of well-accepted biomarkers to predict recovery in veterans with SCI underlines the importance of these investigations.