Macrophage recruitment to acutely injured central nervous system is inhibited by a resident factor: a basis for an immune-brain barrier.

Compared to the peripheral nervous system (PNS), the central nervous system (CNS) of mammals has a poor prospect for regeneration. Accumulating evidence suggests that this is due, in part, to differences in how the immune and nervous systems communicate in response to injury. The macrophage is one of the central cells in this communication with the capacity to respond in a variety of ways depending on the conditions of stimulation. After injury, macrophages enter the CNS much later and in fewer numbers than they do the PNS. It is possible that this late and reduced response is not sufficient to modify the CNS environment to one that is conducive to successful regeneration. In the present study we investigated whether the limited macrophage invasion of injured CNS is due to the presence of an endogenous inhibitory factor that is persistent after injury. Using an in vitro migration assay, we show that rat optic nerve (CNS) is deficient in its ability to attract monocytes as compared to rat sciatic nerve (PNS). We further demonstrate that this deficiency is due to the presence of a soluble inhibitory factor in the CNS. This factor may also cause a subsequent effective difference in those macrophages that are recruited, as is shown by morphological data. The brain-resident factor that inhibits macrophage migration may be the physiological basis of an immune-brain barrier underlying the known phenomenon of immune privilege.