Expression of Pro‐Inflammatory Cytokine and Chemokine mRNA Upon Experimental Spinal Cord Injury in Mouse: an In Situ Hybridization Study

Abstract

Injury to the spinal cord induces a complex cascade of cellular reactions at the local lesion area: secondary cell death and inflammatory reactions as well as scar and cavity formation take place. In order to investigate the molecular features underlying this local wounding response and to determine their pathophysiological implications, we studied the expression pattern of pro‐inflammatory and chemoattractant cytokines in an experimental spinal cord injury model in mouse. We show by in situ hybridization that transcripts for the pro‐inflammatory cytokines TNFα and IL‐1 as well as the chemokines MIP‐1 α and MIP‐1β are upregulated within the first hour following injury. In this early phase, the expression of the pro‐inflammatory cytokines is restricted to cells in the surroundings of the lesion area probably resident CNS cells. While TNFα is expressed in a very narrow time window, IL‐1 can be detected in a second phase in a subset of polymorphonuclear granulocytes which immigrate into the spinal cord around 6 h. Message for the chemokines MIP‐1α and β is expressed in a generalized way in the grey matter of the entire spinal cord around 24 h and gets again restricted to the cellular infiltrate at the lesion site at 4 days following injury. Interestingly, our data suggest that resident CNS cells, most probably microglial cells, and not peripheral inflammatory cells, are the main source for cytokine and chemokine mRNAs. The defined cytokine pattern observed indicates that the inflammatory events upon lesioning the CNS are tightly controlled. The very early expression of pro‐inflammatory cytokine and chemokine messages may represent an important element of the recruitment of inflammatory cells. Additional pathophysiological consequences of the specific cytokine pattern observed remain to be determined.