Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists

Abstract

Here we describe activation of microglia in the rat spinal cord by systemic injections of toll-like receptor agonist polyinosine–polycytidylic acid (poly(I:C), a TLR3 ligand) and R848 (a TLR 7/8 ligand). A significant but transient increase of ED-1 + spinal cord microglia was observed 4 days after a single intraperitoneal (i.p.) injection. Immunostainings by different microglial markers, AIF-1, EMAPII, OX6, P2X 4 receptor (P2X 4R), indicated that microglia were not fully activated and tracing of cell proliferation by 5-bromo-2´-deoxyuridine revealed that only a small fraction of proliferating cells were microglia (less than 5%). Thus, these stimulators of the innate immune system have, after peripheral administration, clearly effects on the innate immune system of the spinal cord. This should be considered in the design of clinical trials, as both TLR ligands have been used in patients. As injections of TLR ligands can be used to modulate immune activity in the spinal cord, such agents might be tools to modulate local regenerative processes in the spinal cord.