Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists.
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 (P2X4R), 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.
Zhang
Zhiren
Z
Institute of Brain Research, University of Tuebingen, Calwer Str. 3, D-72076 Tuebingen, Germany. zhangzhiren@yahoo.com
Trautmann
Katrin
K
Schluesener
Hermann J
HJ
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D053331:Ectodysplasins; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists*; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000819:agonists*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors
D053331:Ectodysplasins; C485473:Eml2 protein, rat; D007093:Imidazoles; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C548228:P2rx4 protein, rat; D011956:Receptors, Cell Surface; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; C489639:TLR7 protein, rat; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; D001973:Bromodeoxyuridine; D011070:Poly I-C; C402365:resiquimod