Research Article: Treatment with Riluzole Restores Normal Control of Soleus and Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic Nerve Crush at Birth

Date Published: January 17, 2017

Publisher: Public Library of Science

Author(s): Wojciech Zmysłowski, Anna M. Cabaj, Urszula Sławińska, Antal Nógrádi.

http://doi.org/10.1371/journal.pone.0170235

Abstract

The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles. S rats with 2–8 and 10–28 MUs that survived in Sol and EDL muscles respectively showed increases in the duration and duty factor of muscle EMG activity and a loss of correlation between the duty factors of muscle activity, and abnormal flexor-extensor co-activation 3 months after SNC. R rats with 5, 6 (Sol) and 15–29 MUs (EDL) developed almost normal EMG activity of both Sol and control EDL muscles, whereas EDL muscles with SNC showed a lack of recovery. R rats with 8 (Sol) and 23–33 (EDL) MUs developed almost normal EMG activities of all four muscles. A subgroup of S rats with a lack of recovery and R rats with almost complete recovery that had similar number of MUs (8 and 24–28 vs 8 and 23–26), showed that the number of MUs was not the only determinant of treatment effectiveness. The results demonstrated that rats with SNC failed to develop normal muscle activity due to malfunction of neuronal circuits attenuating EDL muscle activity during the stance phase, whereas treatment with Riluzole enabled almost normal EMG activity of Sol and EDL muscles during locomotor movement.

Partial Text

Generally, injuries to peripheral nerves lead to impairment of voluntary movement and gait abnormalities followed by muscle atrophy. Without pharmacological therapy to aid functional recovery, patients rely solely on surgical treatment and rehabilitation. Unfortunately, functional outcomes in human patients remain poor. Thus, a great amount of research carried out on animal models has focused on the effects of nerve injury on the structure and function of neuronal circuits involved in muscle control as well as on the search for pharmacological therapies that may improve functional outcomes in patients. Studies on the effect of sciatic nerve crush (SNC) are of special interest, because SNC is an excellent model of the type of nerve injury that occurs frequently during delivery disabling infants for life.

In this study we analyzed for the first time the effects of SNC in new born rats and treatment with Riluzole on soleus and extensor digitorum longus muscle activity during locomotion. Using EMG activity recorded simultaneously from both extensor and flexor muscles of the ankle joint of both hindlimbs we investigated the pattern of spontaneous locomotor behavior along a horizontal runway.

 

Source:

http://doi.org/10.1371/journal.pone.0170235