Fig. 3
From: Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling
Fingolimod (FTY720) enhances myelin thickness independent of its immunomodulatory properties. a Representative images of semi-thin sections used for g-ratio measurements. b G-ratios indicate significantly reduced myelin thickness in crushed nerves of C57BL/6 and Rag1 −/− control animals compared to myelin thickness of contralateral non-crushed nerves. Fingolimod-treated mice showed a reciprocal ratio, with slightly, but even significantly increased myelin thickness in crushed nerves compared to contralateral non-crushed nerves. N = 5/5/4/4/4/4/4/4 animals (from left to right, quantification of one slide per animal). c Treatment of C57BL/6 mice with the autotaxin inhibitor PF-8380 prevented the significant reduction in myelin thickness in regenerating axons normally observed after crush injury (N = 4/4 animals, quantification of one slide per animal). d Representative images of semi-thin sections used for g-ratio measurements at 14-day post-crush in PF-8380 treated mice. e PF-8380 treated C57BL/6 mice did not show an improvement in nerve conduction at 14-day post-crush, pointing to no effect of autotaxin inhibition on axonal regeneration (N = 4/4 animals). f Fingolimod significantly reduces sciatic nerve concentration of 16:0 and 18:0 LPA at 3-h post-injury in crushed nerves of C57BL/6 mice. LPA concentration is still reduced in average at 24-h post-crush. However, in DMSO-treated control mice, nerve injury did not induce invariably increased LPA levels in the crushed nerve compared to contralateral non-crushed nerves. LPA levels are depicted as a ratio calculated from LPA in the crushed nerve and the corresponding contralateral non-crushed nerve (LPAc/LPANC) to account for individual LPA levels between different animals. (N = 4 for each column). g PF-8380 significantly reduces LPA levels at 3-h post-injury in crushed nerves of C57BL/6 mice (N = 5 animals for each column (3 h) or four animals for each column (24 h), respectively) (C crushed, NC non-crushed). Statistical analysis was done by Student’s t test, two-tailed. Data represent mean ± s.e.m. Statistical significance is indicated by asterisks with P ≤ 0.05*, P ≤ 0.01**, and P ≤ 0.001***