Perivascular macrophages (PVM) are hematopoyetic cells that migrate to the brain perivascular space modulating the interactions between the immune and central nervous systems (CNS). Previously, their depletion with the icv administration of the pro-apoptotic drug clodronate encapsulated in liposomes increased the vascular production of the proinflammatory prostaglandin E2 (PGE2), the release of ACTH, corticosterone and fever, induced by the intravenous administration of Lipopolysaccharide (LPS). Further studies also demonstrated a decrease in the synthesis of the anti-inflammatory prostaglandin 15d-PGJ2.

With this background, we decide to deeper explore the mechanisms involved in the anti-inflammatory profile of PVM by depleting them in a model of depression induced by chronic mild stress (CMS) exposure in rats.

Our results showed an increase of the proinflammatory cytokines TNFα, IL-1 and IL-6 at mRNA levels in the prefrontal cortex of the groups of animals where the PVM were depleted, as well as in the protein levels of the pro-inflammatory nuclear factor NF-κB, the enzymatic pro-inflammatory enzymatic sources iNOS, COX-2 and m-PGES-1 and their product PGE2. A concomitant decrease of the 15d-PGJ2 mediator was also observed. In addition, we also checked whether the depletion of PVMs could regulate the expression of molecules implicated in the leukocyte traffic and infiltration in the CNS in our CMS model. Thus, the mRNA levels of the chemokines MCP-1, fractalkine and the adhesion molecule VCAM appeared increased in the animals without PVMs.

In summary, our results could suggest a potential anti-inflammatory role for PVMs in a depression model chronic stress-induced as CMS.