Early events of the inflammatory reaction induced in rat brain by lipopolysaccharide intracerebral injection: relative contribution of peripheral monocytes and activated microglia.

We have previously demonstrated that lipopolysaccharide (LPS) intracerebral injection induced only minimal inflammatory reaction in rat brain, apart from an increased number of 'brain macrophages' observed 24 h after LPS administration [Montero-Menei et al., Brain Res., 653 (1994) 101-111]. However, the nature of these 'brain macrophages' in the inflammatory response is still unclear. The present study focused on the early time-points (from 5 h to 24 h) after LPS injection or stab-lesion, and was aimed at the identification of the peripheral (monocytes) or parenchymal (microglia) origin of these 'brain macrophages'. OX42- and ED1-labeling did not clearly discriminate between monocytes/macrophages and reactive microglia, both cell types being immunoreactive. In other experiments, rats were made aplasic by irradiation prior to lesioning. These experiments clearly demonstrated that LPS induces an intense monocyte recruitment and, to a lesser extent, microglial activation since about 80% of the cells present 24 h after LPS injection consisted of recruited monocytes not observed in aplasic rats. Interestingly, our data show that LPS exerts a sequential dual action by first inhibiting the monocyte recruitment observed 5 h after stab lesion and then enhancing it at 15 h and 24 h after injection. A possible involvement of cytokines, chemokines and adhesion molecules in the mechanisms occurring in the early events of brain inflammatory reaction is discussed.