Chandler L Walker1, Yi Ping Zhang2, Yucheng Liu1, Yiping Li1, Melissa J Walker3, Nai-Kui Liu1, Christopher B Shields2, Xiao-Ming Xu1,3. 1. Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. 2. Norton Neuroscience Institute, Louisville, KY, USA. 3. Medical Neuroscience Program, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract
PURPOSE: Cervical injuries are the most common form of spinal cord injury (SCI), and are often complicated by pathological secondary damage. Therefore, cervical SCI is of great clinical importance for understanding pathology and potential therapies. Here we utilize a weight drop cervical hemi-contusion injury model using a NYU/MASCIS impactor that produced graded anatomical and functional deficits. METHODS: Three groups of rats were established: 1) Sham (laminectomy only) (n = 6), 12.5 mm weight drop (n = 10), and 25 mm weight drop (n = 10) SCI groups. Forelimb functional assessments of grooming ability, cereal manipulation, and forepaw adhesive removal were performed weekly after injury. Using transcranial magnetic motor evoked potentials (tcMMEPs), supraspinal motor stimulations were recorded in both forelimbs and hindlimbs at 5 and 28d post-injury. Lesion volume and myelinated tissue area were assessed through histological analysis. RESULTS: A 12.5 mm weight drop height produced considerable tissue damage compared to Sham animals, while a 25 mm drop induced even greater damage than the 12.5 mm drop (p < 0.05). Forelimb functional assessments showed that increased injury severity and tissue damage was correlated to the degree of forelimb functional deficits. Interestingly, the hindlimbs showed little to no motor function loss. Upon tcMMEP stimulation, surprisingly little motor signal was recorded in the hindlimbs despite outward evidence of hindlimb motor recovery. CONCLUSIONS: Our findings highlight a correlation between anatomical damage and functional outcome in a graded cervical hemi-contusion model, and support a loss of descending motor control from supraspinal inputs and intraspinal plasticity that promote spontaneous hindlimb functional recovery in this model.
PURPOSE: Cervical injuries are the most common form of spinal cord injury (SCI), and are often complicated by pathological secondary damage. Therefore, cervical SCI is of great clinical importance for understanding pathology and potential therapies. Here we utilize a weight drop cervical hemi-contusion injury model using a NYU/MASCIS impactor that produced graded anatomical and functional deficits. METHODS: Three groups of rats were established: 1) Sham (laminectomy only) (n = 6), 12.5 mm weight drop (n = 10), and 25 mm weight drop (n = 10) SCI groups. Forelimb functional assessments of grooming ability, cereal manipulation, and forepaw adhesive removal were performed weekly after injury. Using transcranial magnetic motor evoked potentials (tcMMEPs), supraspinal motor stimulations were recorded in both forelimbs and hindlimbs at 5 and 28d post-injury. Lesion volume and myelinated tissue area were assessed through histological analysis. RESULTS: A 12.5 mm weight drop height produced considerable tissue damage compared to Sham animals, while a 25 mm drop induced even greater damage than the 12.5 mm drop (p < 0.05). Forelimb functional assessments showed that increased injury severity and tissue damage was correlated to the degree of forelimb functional deficits. Interestingly, the hindlimbs showed little to no motor function loss. Upon tcMMEP stimulation, surprisingly little motor signal was recorded in the hindlimbs despite outward evidence of hindlimb motor recovery. CONCLUSIONS: Our findings highlight a correlation between anatomical damage and functional outcome in a graded cervical hemi-contusion model, and support a loss of descending motor control from supraspinal inputs and intraspinal plasticity that promote spontaneous hindlimb functional recovery in this model.
Entities:
Keywords:
Cervical hemi-contusion; functional recovery; spinal cord injury; tcMMEP; transcranial magnetic motor evoked potentials