myelin-basic-protein and Intervertebral-Disc-Displacement

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

CSF levels of myelin basic protein (MBP) and intrathecally produced CSF IgG (de novo IgG) were measured in 11 chronic progressive multiple sclerosis patients with a deteriorating course of the disease for at least 6 months preceding observation and a reference group of 17 neurological patients suffering from disc herniation. In the multiple sclerosis patients, CSF levels were determined just before and once in the period 3 to 10 weeks after the start of an immunosuppressive treatment with cyclophosphamide and prednisone. For multiple sclerosis patients the CSF MBP levels before treatment were significantly higher than for controls. The CSF MBP levels after the treatment were nearly all within the control range. The abnormal high concentration of intrathecally produced CSF IgG (de novo IgG) in multiple sclerosis patients was reduced after treatment. A correlation between CSF MBP and CSF de novo IgG in multiple sclerosis patients could not be demonstrated. If CSF MBP is an indicator of the (activity of) myelin breakdown in the brain, it can be concluded that an intensive immunosuppressive treatment in combination with prednisone has, at least, a short-term, beneficial effect on the amount of demyelinisation and possibly on the disease activity.

Topics: Adult; Aged; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunoglobulin G; Intervertebral Disc Displacement; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Prednisone