The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)
Histological and functional characterization of cervical spinal cord injury after graded contusion
Author ORCID Identifier
Date of Graduation
Masters of Science (MS)
Qi Lin Cao, M.D.
Radbod Darabi, Ph.D.
Ying Liu, M.D., Ph.D.
Qingchun Tong, Ph.D.
Jiaqian Wu, Ph.D.
Most spinal cord injuries (SCIs) are cervical contusions and result in deficits for both locomotion and reaching and grasping functions. Previous studies have characterized histological and functional deficits in locomotion using primarily thoracic contusions, but most patients have cervical injuries. Damage to descending long spinal tracts (dLSTs) is one well-established cause of functional loss after SCI and has been explored in laceration and transection models, but these are not clinically relevant. In this study, I will explore the histological and functional deficits after graded cervical hemicontusion SCI and examine the potential contribution of different histological deficits to forelimb function after injury. B6 mice received a clinically relevant cervical hemicontusion graded at either 50, 70, or 90 kDyne force and were then tested weekly in complex horizontal ladder (cHL), rotarod, grooming, and either pellet reaching or pasta handling. Our results showed greater injury severity significantly increased missteps in cHL, reduced stepping time in rotarod, and decreased grooming ability. Histological analyses revealed that injury severity significantly increased the injury size by fibronectin-immunoreactivity (IR) and gray matter loss by MAP2-IR. There was a significant correlation between lesion size and gray matter loss and injury severity. Correlations between histology and behavior outcomes showed a significant correlation between the percentage of missteps in cHL, injury severity, and lesion size. Additionally, both rotarod score and grooming score correlated with injury severity, lesion size, and gray matter loss. This study characterizes a clinically relevant injury model, shows that graded cervical hemicontusions result in degrees of functional and anatomical loss, and serves as a baseline to aid future studies in identifying therapeutic targets to promote functional recovery after cervical SCI and improve the quality of life for patients with SCI.
SCI, cervical, forelimb, histology, functional recovery, contusion