(A) Experimental scheme for in vivo AIH: 6 10min hypoxic
episodes (8% oxygen) with equivalent 10min normoxic intervals. Green bar indicates
10 min hypoxic condition and black bar indicates 10 min normoxic condition (AIH total
duration=120 min). Control mice followed the same 120 min regime under normoxia. SNC:
sciatic nerve crush. (B) Western blot analysis of mouse L4 and L5 DRGs treated for 120 min
of normoxia (No) or hypoxia (Hx) using the AIH protocol. (C) Quantifications of protein
level of HIF-1α and p-JNKs (n=3 for each condition;
***p<0.001, **p<0.01 by
t-test; mean±SEM). (D) Representative longitudinal sections of
sciatic nerves from control or HIF1AcKO mice, dissected 3 days after injury with or
without daily AIH and immunostained for SCG10 and βIII tubulin. Scale bar,
500µm. (E and F) In vivo regeneration index calculated from (D)
(n=7 and 10 for normoxia and hypoxia from control mice,
n=10 and 8 for normoxia and hypoxia from HIF1AcKO mice;
*p<0.05 by one-way ANOVA with Tukey test; mean±SEM; ns,
not significant). (G) Motor axons reinnervation assays. EHL muscles of
thy1-YFP-16 mice dissected 12 days after sciatic nerve injury with or
without daily AIH were stained with Alexa Fluor 647-conjugated α-Bungarotoxin
(αBTX). Scale bar, 100µm. (H) Quantification of percentage of
axon-non-occupied (N) and axon-re-occupied NMJ end plates (O) (n=15 for
each condition; box, 25 to 75%; whisker, standard deviation; closed circle, mean;
***p<0.001 by one-way ANOVA with Tukey test; ns, not
significant).