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The common neurotrophin receptor, p75NTR , has been proposed to be an inhibitor of axon regeneration after peripheral nerve injury, but whether this effect is on the regenerating axons, immune cells migrating into the injury site, or cells in the pathway surrounding the axons is not clear. Cut nerves in mice expressing fluorescent proteins in axons were repaired with grafts from non-fluorescent hosts to study axon elongation when p75NTR was eliminated separately from axons and immune cells in the proximal stump of cut nerves, from cells in the regeneration pathway, or both. Two weeks later, axons from wild type mice regenerating into grafts devoid of p75NTR had elongated more than twice as far as axons in grafts from wild type mice. No enhancement of regeneration of axons in p75NTR knockout mice was observed, whether nerves were repaired with grafts from wild type mice or from p75NTR knockout mice. To evaluate whether inhibition of p75NTR could be used to improve regeneration, nerves in wild type mice repaired without grafts were exposed to a specific inhibitor of the p75NTR receptor, LM11A-31, at the time of nerve repair. This local blockade of p75NTR resulted in successful regeneration of axons of nearly three times as many motoneurons and reinnervation of twice as many muscle fibers by regenerating motor axons as untreated controls. Expression of p75NTR surrounding regenerating axons contributes to poor regeneration during the first 2 weeks after peripheral nerve injury. Inhibition of p75NTR might be a therapeutic target for treatments of peripheral nerve injuries.

BACKGROUND Downslope walking (DSW) is an eccentric-based exercise intervention that promotes neuroplasticity of spinal reflex circuitry by inducing depression of Soleus Hoffman (H)-reflexes in young, neurologically unimpaired adults. OBJECTIVE The objective of the study was to evaluate the effects of DSW on spinal excitability (SE) and walking function (WF) in people with multiple sclerosis (PwMS). METHODS Our study comprised two experiments on 12 PwMS (11 women; 45.3±11.8 years). Experiment 1 evaluated acute effects of a single 20-minute session of treadmill walking at three different walking grades on SE, 0% or level walking (LW), - 7.5% DSW, and - 15% DSW. Experiment 2 evaluated the effects of 6 sessions of DSW, at - 7.5% DSW (with second session being - 15% DSW) on SE and WF. RESULTS Experiment 1 showed significantly greater acute % H-reflex depression following - 15% DSW compared to LW (p = 0.02) and - 7.5% DSW (p = 0.05). Experiment 2 demonstrated significant improvements in WF. PwMS who showed greater acute H-reflex depression during the - 15% DSW session also demonstrated greater physical activity, long-distance WF, and the ability to have greater H-reflex depression after DSW training. Significant changes were not observed in regards to SE. CONCLUSIONS Though significant changes were not observed in SE after DSW training, we observed an improvement in WF which merits further investigation of DSW in PwMS.

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can be used to evaluate descending corticomotor influences on spinal reflex excitability through modulation of the Hoffman reflex (H-reflex). The purpose of this study was to characterize between-session reliability of cortical, spinal, and cortical-conditioned spinal excitability measures collected from the soleus muscle. Thirteen able-bodied young adult participants were tested over four sessions. Intraclass correlation coefficients were calculated to quantify between-session reliability of active motor threshold (AMT), unconditioned H-reflexes (expressed as a percentage of Mmax), and conditioned H-reflexes using short-latency facilitation (SLF) and long-latency facilitation (LLF). Pearson correlation coefficients were calculated to assess associations between H-reflex facilitation and unconditioned H-reflex amplitude. Between-session reliability for SLF (ICC = 0.71) was higher than for LLF (ICC = 0.45), was excellent for AMT (ICC = 0.95), and was moderate for unconditioned H-reflexes (ICC = 0.63). Our results suggest moderate-to-good reliability of SLF and LLF to evaluate cortical influences on spinal reflex excitability across multiple testing sessions in able-bodied individuals.

This article outlines the novel hypothesis that exercise promotes axon regeneration after peripheral nerve injury through neuronal brain-derived neurotrophic factor (BDNF), and there are three required means of promoting BDNF expression: 1) increased signaling through androgen receptors, 2) increased cAMP-responsive element-binding protein expression, and 3) increased expression of the transcription factor SRY-box containing gene 11.

Downslope walking (DSW) causes H-reflex depression in healthy adults, and thus may hold promise for inducing spinal reflex plasticity in people with Multiple Sclerosis (PwMS). The study purpose was to test the hypothesis that DSW will cause acute depression of spinal excitability in PwMS. Soleus H-reflexes were measured in PwMS (n = 18) before and after 20 min of treadmill walking during three visits. Participants walked on a different slope each visit [level: 0% level walking (LW), upslope: +7.5% treadmill walking with an upslope (USW) or downslope: −7.5% (DSW)]. The soleus Hmax/Mmax ratio was used to measure spinal excitability. Heart rate and ratings of perceived exertion (RPE) were measured during walking. DSW induced the largest change in spinal excitability (a 26.7% reduction in soleus Hmax/Mmax (p = 0.001)), although LW also reduced Hmax/Mmax (-5.3%, p = 0.05). Heart rate (p

The purpose of this study was to test the hypothesis that downslope treadmill walking decreases spinal excitability. Soleus H-reflexes were measured in sixteen adults on 3 days. Measurements were taken before and twice after 20 min of treadmill walking at 2.5 mph (starting at 10 and 45 min post). Participants walked on a different slope each day [level (Lv), upslope (Us) or downslope (Ds)]. The tibial nerve was electrically stimulated with a range of intensities to construct the M-response and H-reflex curves. Maximum evoked responses (Hmax and Mmax) and slopes of the ascending limbs (Hslp and Mslp) of the curves were evaluated. Rate-dependent depression (RDD) was measured as the % depression of the H-reflex when measured at a rate of 1.0 Hz versus 0.1 Hz. Heart rate (HR), blood pressure (BP), and ratings of perceived exertion (RPE) were measured during walking. Ds and Lv walking reduced the Hmax/Mmax ratio (P = 0.001 & P = 0.02), although the reduction was larger for Ds walking (29.3 ± 6.2% vs. 6.8 ± 5.2%, P = 0.02). The reduction associated with Ds walking was correlated with physical activity level as measured via questionnaire (r = −0.52, P = 0.04). Us walking caused an increase in the Hslp/Mslp ratio (P = 0.03) and a decrease in RDD (P = 0.04). These changes recovered by 45 min. Exercise HR and BP were highest during Us walking. RPE was greater during Ds and Us walking compared to Lv walking, but did not exceed “Fairly light” for Ds walking. In conclusion, in healthy adults treadmill walking has a short-term effect on soleus H-reflex excitability that is determined by the slope of the treadmill surface.