Attenuated Reactive Gliosis And Enhanced Functional Recovery Following Spinal Cord Injury In Null Mutant Mice Of Platelet-activating Factor Receptor

Background:Reactive gliosis, also known as glial scar formation, is a cell reaction after CNSinjury. In this progress, both activated microgila and astreocytes participate theformation and the regulation of glial scar. After injury, multisourced cytokines andchemokines released in acute inflammatory phase thread through blood-brain barrierand activate microglia and astrocytes, and eventually result in gliosis. One hand, thescar can protect the adjacent tissue by restricting the inflammatory reaction in alimited area, on the other hand, it also block the pathway of axon regeneration andremyelination. Platelet activating factor (PAF)，also known as glial scar formation is aunique phosphoglycerine that mediates the biological functions of both immune andnervous systems. Excessive PAF plays an important role in neural injury via itsspecific receptor (PAFR). In this study, we hypothesized that PAF signaling activatesreactive gliosis after spinal cord injury (SCI) and blocking the PAF pathway wouldmodify the glia scar formation and promote functional recovery.Results:PAF microinjected into the normal wild-type spinal cord induced adose-dependent activation of microglia and astrocytes. In the SCI mice, PAFR nullmutant mice showed a better functional recovery in grip and rotarod performancesthan wild-type mice. Although both microglia and astrocytes were activated after SCIin wild-type and PAFR null mutant mice, expressions of IL-6, vimentin, nestin andGFAP were not significantly elevated in PAFR null mutants. Disruption of PAFsignaling inhibited the expressions of proteoglycan CS56and neurocan (CSPG3).Intriguingly, compared to the wild-type SCI mice, less axonal retraction/dieback at7dpi but more NFH-labeled axons at28dpi were found in the area adjacent to theepicenter in PAFR null mutant SCI mice. Moreover, treatment with PAFR antagonistGinkgolide B (GB) at the chronic phase rather than acute phase enhanced thefunctional recovery in the wild-type SCI mice. Conclusion:These findings suggest that PAF signaling participates in reactive gliosis afterSCI, and blocking of this signaling enhances functional recovery and to some extentmay promote axon regrowth.