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[Identification of macrophage migration inhibitory factor (MIF) in rat spinal cord and its kinetics on experimental
1Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan.
Background:
Among spinal cord injuries, secondary injury is considered to be a "reversible" process and seems to be a key target for the treatment of spinal cord injury. Recently, macrophage migration inhibitory factor (MIF) has been reevaluated as being one of the most important cytokines which act during wound healing, proliferation and differentiation of cells. However, the expression of MIF in the spinal cord has not been investigated yet.
Purpose:
The purpose of this paper is to demonstrate the MIF expression in normal rat spinal cord and to evaluate the kinetics of MIF after spinal cord injury.
Materials & Methods:
Female Wistar (280-320 g) rats were studied. Spinal cord injury was made by the clip compression method at the level of C7/Th1 (56 g, For 1 min.). The expression of MIF was examined by immunohistochemistry and northern blot analysis. MIF content in the cerebrospinal fluid (CSF) was measured by enzyme-linked immunosorbent assays (ELISA). Furthermore, to examine the MIF function on neuronal cell, cell proliferation assay (MTS assay) was carried out using PC12, pheochromocytoma cell line, and LN444, glioblastoma cell line, in the presence of anti-MIF monoclonal antibody.
Results:
MIF stain was positive in normal rat spinal cord white matter. The expression of MIF decreased between 1 hour and 6 hours after injury. It was found to have re-appeared 24 hours after injury. The kinetics of MIF mRNA expression showed reverse-correlation with those of the MIF positive stain. MIF content in CSF was found to be elevated soon after injury. MTS assay suggested that MIF had some proliferative function on neuronal cells.
Conclusion:
MIF exists in the rat white matter. And it's immediately released into the CSF and then re-synthesized 24-hr after injury. MIF shows a cell proliferative function on neuronal cells. These results suggest that MIF plays an important role for secondary spinal cord injury.
Insights
Macrophage migration inhibitory factor (MIF) is present in rat white matter and released into cerebrospinal fluid after spinal cord injury. MIF reappears 24 hours post-injury and promotes neuronal cell proliferation, suggesting a key role in secondary spinal cord injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Context:
- Secondary spinal cord injury (SCI) is a critical therapeutic target.
- Macrophage migration inhibitory factor (MIF) is a key cytokine in wound healing and cell proliferation.
- MIF expression in the spinal cord remains largely uninvestigated.
Purpose:
- To investigate macrophage migration inhibitory factor (MIF) expression in normal rat spinal cord.
- To determine the temporal changes (kinetics) of MIF following spinal cord injury.
Summary:
- MIF is detected in the white matter of normal rat spinal cords.
- Following SCI, MIF expression initially decreases then reappears 24 hours post-injury.
- MIF levels in cerebrospinal fluid increase immediately after injury.
- In vitro assays indicate MIF promotes neuronal cell proliferation.
Impact:
- These findings reveal MIF's presence and dynamic expression in the spinal cord.
- MIF's role in neuronal proliferation suggests its involvement in secondary SCI pathogenesis.
- MIF represents a potential therapeutic target for mitigating secondary spinal cord injury.
