The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury.

The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury. Exp Neurol. 2017 Apr 23;: Authors: Stivers NS, Pelisch N, Orem BC, Williams J, Nally JM, Stirling DP Abstract Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI. To test this hypothesis, we documented acute changes in microglia, axons, and oligodendroglia over time using two-photon excitation and an ex vivo laser-induced SCI (LiSCI) model. We utilized double transgenic mice that express GFP in either microglia or oligodendroglia, and YFP in axons, and we applied the lipophilic fluorescent dye (Nile Red) to visualize myelin. We found that treatment with Pam3CSK4 initiated one hour after injury induced a significant increase in the extent and timing of the microglial response to injury compared to vehicle controls. This enhanced response was observed 2 to 4h following SCI and was most prominent in areas closer to the ablatio...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research