myelin-basic-protein and Intervertebral-Disc-Degeneration

Spinal cord injury (SCI) represents a devastating central nervous system disease that still lacks sufficient therapies. Here, dogs are increasingly recognized as a preclinical animal model for the development of future therapies. The aim of this study was a detailed characterization of axonopathy in canine intervertebral disc disease, which produces a mixed contusive and compressive injury and functions as a spontaneous translational animal model for human SCI. The results revealed an early occurrence of ultrastructurally distinct axonal swelling. Immunohistochemically, enhanced axonal expression of β-amyloid precursor protein, non-phosphorylated neurofilament (n-NF) and growth-associated protein-43 was detected in the epicenter during acute canine SCI. Indicative of a progressive axonopathy, these changes showed a cranial and caudally accentuated spatial progression in the subacute disease phase. In canine spinal cord slice cultures, immunoreactivity of axons was confined to n-NF. Real-time quantitative polymerase chain reaction of naturally traumatized tissue and slice cultures revealed a temporally distinct dysregulation of the matrix metalloproteinases (MMP)-2 and MMP-9 with a dominating expression of the latter. Contrasting to early axonopathy, diminished myelin basic protein immunoreactivity and phagocytosis were delayed. The results present a basis for assessing new therapies in the canine animal model for translational research that might allow partial extrapolation to human SCI.

Topics: Animals; Axons; Disease Models, Animal; Dogs; Female; GAP-43 Protein; Gene Expression Regulation; Hypoxanthine Phosphoribosyltransferase; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Macrophages; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Microglia; Microscopy, Electron, Transmission; Microscopy, Immunoelectron; Myelin Basic Protein; Neurofilament Proteins; Organ Culture Techniques; Peptide Elongation Factor 1; Phagocytes; RNA, Messenger; Spinal Cord; Spinal Cord Injuries; Statistics, Nonparametric