scholarly journals The differential effects of pathway- versus target-derived glial cell line–derived neurotrophic factor on peripheral nerve regeneration

2010 ◽  
Vol 113 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Christina K. Magill ◽  
Amy M. Moore ◽  
Ying Yan ◽  
Alice Y. Tong ◽  
Matthew R. MacEwan ◽  
...  

Object Glial cell line–derived neurotrophic factor (GDNF) has potent survival effects on central and peripheral nerve populations. The authors examined the differential effects of GDNF following either a sciatic nerve crush injury in mice that overexpressed GDNF in the central or peripheral nervous systems (glial fibrillary acidic protein [GFAP]–GDNF) or in the muscle target (Myo-GDNF). Methods Adult mice (GFAP-GDNF, Myo-GDNF, or wild-type [WT] animals) underwent sciatic nerve crush and were evaluated using histomorphometry and muscle force and power testing. Uninjured WT animals served as controls. Results In the sciatic nerve crush, the Myo-GDNF mice demonstrated a higher number of nerve fibers, fiber density, and nerve percentage (p < 0.05) at 2 weeks. The early regenerative response did not result in superlative functional recovery. At 3 weeks, GFAP-GDNF animals exhibit fewer nerve fibers, decreased fiber width, and decreased nerve percentage compared with WT and Myo-GDNF mice (p < 0.05). By 6 weeks, there were no significant differences between groups. Conclusions Peripheral delivery of GDNF resulted in earlier regeneration following sciatic nerve crush injuries than that with central GDNF delivery. Treatment with neurotrophic factors such as GDNF may offer new possibilities for the treatment of peripheral nerve injury.

2014 ◽  
Vol 2014 ◽  
pp. 1-11
Author(s):  
Liang Shu ◽  
Jingjing Su ◽  
Lingyan Jing ◽  
Ying Huang ◽  
Yu Di ◽  
...  

Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.


2021 ◽  
Vol 9 (A) ◽  
pp. 1006-1010
Author(s):  
Agus Roy Rusly Hariantana Hamid ◽  
Sri Maliawan ◽  
DPG Purwa Samatra ◽  
I Nyoman Mantik Astawa ◽  
I Made Bakta ◽  
...  

BACKGROUND: The role of neurotrophic factors (brain-derived neurotrophic factors and glial cell line-derived neurotrophic factors) and early electrical stimulation (EES) in the injured nerve has found promising in several studies. However, there is still limited knowledge about the effect of EES in the distal part of the nerve to sustain this level of expression of growth factors. AIM: We aim to evaluate the effects of EES in in neural regeneration by measuring the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in animal model. METHODS: The research was conducted starting from April to May 2021 using male Wistar rats. Using general anesthesia, the sciatic nerve was cut. The intervention group was treated with EES in the distal stump, right after nerve resection (20 Hz, 1–2 mA, 2–5 s), while the control group received no treatment after nerve resection. A reoperation on day 3 was performed in both groups to measure BDNF and GDNF expression level of the distal nerve tissue by ELISA as well as histopathological examination of sprouting axons of the injured proximal nerve. RESULTS: A total of 32 samples were included in the study. A statistically significant levels of GDNF is found higher in the EES group (n = 16) than the control group (n = 16) (35. 71 pg/100 mg, confidence interval (CI) 95% 23.93, 47.48, p < 0.05). The number of sprouting axons is found lower in the EES group (p < 0.05). The BDNF level is similar between the two groups, however not significant. After a subgroup analysis, it was found that the greater the level of GDNF, the fewer the axon sprouts in both groups (fewer axon group 58.35 [n = 22, CI 95% 45.14, 71.55] vs. more axon group 47.14 [n = 10, CI 95% 35.33, 58.95]), p < 0.05. CONCLUSION: The EES proves its benefit in accelerating the axonal regeneration by increasing the expression GDNF in the distal nerve stumps in the electrical excited degenerated sciatic nerve in the rat model.


2005 ◽  
Vol 95 (2) ◽  
pp. 537-543 ◽  
Author(s):  
Asako Hase ◽  
Fumiaki Saito ◽  
Hiroki Yamada ◽  
Ken Arai ◽  
Teruo Shimizu ◽  
...  

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