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Published on: September 21, 2021
Microglia activation in rat spinal cord by systemic injection of TLR3 and TLR7/8 agonists
Zhiren Zhang1, Katrin Trautmann, Hermann J Schluesener
1Institute of Brain Research, University of Tuebingen, Calwer Str. 3, D-72076 Tuebingen, Germany. zhangzhiren@yahoo.com
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 (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.
Insights
Systemic administration of toll-like receptor (TLR) ligands like poly(I:C) and R848 transiently increases spinal cord microglia. These innate immune stimulators may offer tools for modulating spinal cord regeneration and should be considered in clinical trial designs.
Area of Science:
- Neuroimmunology
- Innate Immunity
- Spinal Cord Research
Background:
- Toll-like receptors (TLRs) are key components of the innate immune system.
- TLR agonists like poly(I:C) and R848 are used to study immune responses.
- Understanding peripheral immune modulation of the central nervous system is crucial.
Purpose of the Study:
- To investigate the effects of systemic TLR agonist administration on spinal cord microglia in rats.
- To assess the extent of microglial activation and proliferation following TLR stimulation.
- To explore the potential of TLR ligands in modulating spinal cord immune activity and regeneration.
Main Methods:
- Systemic intraperitoneal injections of poly(I:C) and R848 in rats.
- Analysis of microglial populations using ED-1 staining.
- Immunostaining with microglial markers (AIF-1, EMAPII, OX6, P2X4R).
- Cell proliferation tracing using 5-bromo-2'-deoxyuridine (BrdU).
Main Results:
- A significant but transient increase in ED-1+ microglia was observed 4 days post-injection.
- Immunostaining indicated incomplete microglial activation.
- BrdU tracing revealed that less than 5% of proliferating cells were microglia.
Conclusions:
- Systemic TLR agonists induce transient changes in spinal cord innate immunity.
- These findings have implications for clinical trial design involving TLR ligands.
- TLR ligands may serve as potential tools for modulating spinal cord regeneration.
