Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging

Abstract

Introduction: The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. Methods: Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. Results: Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. Discussion: Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values.

Delivery of adipose‐derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration

“…The group treated with ASCs delivered in PBS had the second smallest number of DAPI + objects; it may be that a decreased number of surviving ASCs with this delivery method leads to a reduced efficacy of the hypothesized immunomodulatory effects of these cells. Increasing interest in the role of immunomodulation in peripheral nerve regeneration has led to a number of studies demonstrating the importance of “fine‐tuning” this response.…”

“…Zheng et al . were recently able to demonstrate improvement in regeneration with treatment with both proinflammatory and anti‐inflammatory agents, allowing for both rapid Wallerian degeneration and a decrease in T‐cell proliferation and inflammatory cytokines.…”

“…In addition, immunomodulatory effects of ASCs have been described, particularly in the context of transplant medicine . The importance of regulation of the immune response in peripheral nerve regeneration—both the benefit of appropriate clearance of degenerating material and the requirement to prevent excessive inflammation—is an area of ongoing investigation …”

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

“…On the other hand, administration of the immunosuppressant tacrolimus (FK506) can also promote peripheral nerve regeneration and functional recovery 11,12 . FK506 can prevent T‐cell proliferation 13 and inhibit T‐cell function by binding to FK‐binding proteins (FKBPs) 14 . It has been shown that FK506 can promote peripheral nerve regeneration through suppression of fibroblast proliferation, which is activated by inflammatory cytokines at the site of nerve repair, 11,15 and can exert a maximal effect on nerve regeneration when administered at a high dose (5 to 10 mg/kg/d) after nerve crush injury in rats 12 .…”

“…It has been shown that FK506 can promote peripheral nerve regeneration through suppression of fibroblast proliferation, which is activated by inflammatory cytokines at the site of nerve repair, 11,15 and can exert a maximal effect on nerve regeneration when administered at a high dose (5 to 10 mg/kg/d) after nerve crush injury in rats 12 . Recently, the sequential use of LPS and FK506 has been reported to be able to exert synergistic repair effects in neurotmesis 13 …”