Immune Response And Signals Mediating Of MCP-1 After Spinal Cord Injury (SCI)

In the context of a spinal cord injury (SCI), accumulating evidence suggests that immune cells recruited to the lesion site may exacerbate tissue damage. Given that immune responses that rapidly develop after SCI may lead to microgliosis and cause exacerbation of tissue damage, it is important to define the exact role (s) of individual immune molecules during the course of pathological conditions and the mechanisms by which their production is regulated. A better knowledge of the functions of these molecules could allow the identification of new potential targets to treat CNS injuries by either promoting axonal growth or reducing tissue loss.This subject is aimed to study the definitive immune response in vivo and signals mediating of MCP-1 after spinal cord injury so as to provide experimental evidence for the clinical treatment on sequential spinal cord injury, improving the spinal cord repairing after injury. The purpose of this study is to examine the spatio-temporal distribution of the monocyte chemoattractant protein-1 (MCP-1), identify the signals that mediate MCP-1 expression after SCI, 5 studies were performed:1,the spatio-temporal distribution of the monocyte chemoattractant protein-1 (MCP-1) after the mice spinal cord injury. 2,the cellular sources of the monocyte chemoattractant protein-1 (MCP-1) at different courses after the mice spinal cord injury. 3,the roles of MyD88 and IL-1R express MCP-1 mRNA following the acute spinal cord injury by signaling pathway, 4,the role of Purinergic Receptor P2X7 express MCP-1 mRNA at different courses following the acute spinal cord injury. 5,the role of monocyte chemoattractant protein-1 (MCP-1) on microglia and macrophage after (MCP-1) injecton at the mice spinal cord.The main experimental methods : contusion of 70 kdyn was performed on the vertebral column using the Infinite Horizon (IH) SCI device , microinjection of MCP-1 into the normal spinal cord dorsal column using a glass micropipette with a tip diameter of 30μm, depending on the experiment performed, spinal cord injured and Microinjection of MCP-1 mice were sacrificed by perfusion at different courses post-surgery, a spinal cord segment of 12 mm centered over the lesion site was cut in several series of 30-μm-thick coronal sections using a cryostat. Sections were collected directly onto slides, the three-dimensional (3D) reconstruction of the lesion, ISH was carried out to detect mRNAs coding for the chemokine MCP-1, All sections were prehybridized, hybridized and posthybridized in parallel to equalize background intensity, To identify the populations of cells expressing MCP-1 and IL-1 mRNAs, ISH was combined with immunofluorescence. The main results of this study were as follows:1,a rapid and widespread expression of MCP-1 after the mice spinal cord injury, the MCP-1 expression depended on the time courses during the phase from 3hours to 4days the MCP-1 expression increased significantly. 2,the spatial changes of MCP-1 expression after the mice spinal cord injury which were responsible by specific immune cells. 3,resident CNS cells located nearby the site of injury, such as endothelial cells, perivascular microglial cells, astrocytes, and neurons are responsible for the rapid expression of MCP-1 following spinal cord trauma. Immune cells that are recruited within damaged areas such as macrophages, appear however to be mainly accountable for the expression of MCP-1 during the subacute and chronic phases of SCI.4,MCP-1 expression was controlled by MyD88 and IL-1R through signaling pathways at the early acute (3 hours) and chronic (28 days) phases of SCI and still there is other pathways partly responsible for MCP-1 expression. 5,MCP-1 expression was not declined significantly between P2X7 receptor knock out mice and control ones, some other signaling pathways are responsible for MCP-1 expression after that. 6,MCP-1 stimulate the recruitment and activation of macrophages and microglia.The main conclusions in the study:1,The expression of MCP-1 after the mice spinal cord injury depended on the time courses and the spatial changes; 2,Different immune cells were responsible for the expression of MCP-1 at specific courses after the mice spinal cord injury; 3,MyD88 and IL-1R signaling pathway controlled the expression of MCP-1 mRNA at different phases following a spinal cord injury; 4,P2X7 receptor signaling was not the key role mediated the MCP-1 expression by activation the IL-1βR; 5,MCP-1 stimulates macrophages recruitment and microglia/macrophages activation.Such knowledge will be important to further define and understand the molecular and cellular events involved in the development of the inflammatory response following a SCI.