|Myelotomy with intramedullary hemorrhagic necrosis removal (MIHN) as a therapeutic strategy in a porcine model of traumatic spinal cord injury
The porcine model has been proposed as a large animal model for testing new therapeutic interventions in a species with spinal cord dimensions and physiology like humans. It is hoped that promising interventions developed in this model will have high translational potential for humans. Over the last year and a half, we have collaborated with Dr. Brian Kwon and his research group at the International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada, who developed a porcine SCI model. With their assistance, we have established their porcine SCI model at the University of Louisville Kentucky Spinal Cord Injury Research Center (KSCIRC). We have developed a comprehensive set of protocols, including:
Using this protocol, we have performed preliminary studies to thoroughly characterize this preclinical porcine model for new therapeutic strategies in SCI. Our preliminary in vivo MRI data of both the 20-cm and 40-cm weight drop injuries showed cord signal change, hemorrhage, and edema, very much reminiscent of human SCI MRI imaging. Serial MRI showed decreased swelling and reduction of edema and blood over the 12-week follow-up period during which there were significant improvements in hindlimb weight support and gait kinematics making this an excellent translational model to be used in this project.
In the human study mentioned above the first study evaluating this therapeutic approach, beneficial clinical effects were observed after MIHN followed by intra-injury cavity scaffold placement. There remains a likely possibility that the beneficial effects could be from MIHN alone, however, this control group is not being evaluated in the human study. Besides the limited literature about MIHN as a therapeutic approach for SCI, other gaps in knowledge arise from the fact that the outcome assessments in previous studies focused primarily on locomotor functional recovery and histological analysis without MRI neuroimaging, electrophysiological assessments, or cystometric bladder function evaluation. In summary, significant gaps exist regarding this promising therapeutic approach, and our goal is to address these gaps using a large animal porcine SCI model.
Our primary aim is to assess the effects of MIHN as a potential treatment for SCI. The benefit(s) and adverse impact(s) of MIHN on axon and cell body sparing, cord edema, injury and cord volumes, CSF flow, neural electrophysiological function and injury histopathology will be determined with comparisons to non-myelotomy injured pigs. Bladder function will be assessed using cystometric urodynamic testing.
|Adult NeuroRecovery Program