scholarly journals A guide to reducing adverse outcomes in rabbit models of sciatic nerve injury

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Elisabeth Orozco ◽  
Koichi Masuda ◽  
Sameer B. Shah

Abstract Background Peripheral nerve damage can have debilitating consequences. Rabbit sciatic nerve transection models allow the effective evaluation of surgical repair strategies for large nerve gaps. Despite advantages in size, ease of handling, and functional utility, rabbits can suffer from a number of side effects that affect animal welfare and the quality of scientific inquiry. Such side-effects, which include pressure ulcers and traumatic damage to the foot, are primarily a consequence of insensitivity of the distal hindlimb following sciatic nerve injury. In this study, we present a number of methodologies for identifying, treating, and preventing unintended adverse effects in rabbit sciatic nerve injury models. Results First, we categorize pressure ulcers according to their severity and describe the deployment of a padded bandaging technique to enable ulcer healing. We also introduce a proactive bandaging approach to reduce the likelihood of pressure ulcer formation. Second, we define phenotypes that distinguish between foot injuries resulting from self-mutilation (autotomy) from those caused by incidental traumatic injury secondary to sensori-motor damage. Finally, we detail an effective strategy to reduce the usage of Elizabethan collars; through a gradual weaning protocol, their usefulness in preventing autotomy is retained, while their propensity to impede rabbit grooming and cause abrasion-injury to the neck region is minimized. Conclusions We suggest that application of these methods offer a practical and systematic approach to avoid adverse side effects associated with rabbit sciatic nerve damage, enabling improved animal welfare and scientific outcomes in a powerful nerve injury model.

2018 ◽  
Vol 18 (4) ◽  
pp. 687-693 ◽  
Author(s):  
Tiansheng Shi ◽  
Jing-Xia Hao ◽  
Zsuzsanna Wiesenfeld-Hallin ◽  
Xiao-Jun Xu

Abstract Background and aims The clinical management of neuropathic pain remains a challenge. We examined the interaction between gabapentin and NMDA receptor antagonists dextromethrophan and MK-801 in alleviating neuropathic pain-like behaviors in rats after spinal cord or sciatic nerve injury. Methods Female and male rats were produced with Ischemic spinal cord injury and sciatic nerve injury. Gabapentin, dextromethorphan, MK-801 or drug combinations were injected with increasing doses. Mechanical response thresholds were tested with von Frey hairs to graded mechanical touch/pressure, and ethyl chloride spray was applied to assess the cold sensitivity before and after injuries. Results In spinally injured rats, gabapentin and dextromethorphan did not affect allodynia-like behaviors at doses of 30 and 20 mg/kg, respectively. In contrast, combination of 15 or 30 mg/kg gabapentin with dextromethorphan at 10 mg/kg produced total alleviation of allodynia to mechanical or cold stimulation. Further reducing the dose of gapapentin to 7.5 mg/kg and dextromethorphan to 5 mg/kg still produced significant effect. MK-801, another NMDA receptor antagonist, also enhanced the effect of gabapentin in spinally injured rats. Similar synergistic anti-allodynic effect between dextromethorphan and gabapentin was also observed in a rat model of partial sciatic nerve injury. No increased side effect was seen following the combination between gabapentin and dextromethorphan. Conclusions In conclusion, the present study suggested that combining NMDA receptor antagonists with gabapentin could provide synergistic effect to alleviate neuropathic pain and reduced side effects. Implications Combining NMDA receptor antagonists with gabapentin may provide a new approach in alleviating neuropathic pain with increased efficacy and reduced side effects.


2014 ◽  
Vol 125 (11) ◽  
pp. 855-860 ◽  
Author(s):  
Chao Hu ◽  
Taogen Zhang ◽  
Zhouming Deng ◽  
Bin Ren ◽  
Lin Cai ◽  
...  

2020 ◽  
Vol 14 (4) ◽  
pp. 263-269
Author(s):  
A. A. Starinets ◽  
E. L. Egorova ◽  
A. A. Tyrtyshnaia ◽  
I. V. Dyuisen ◽  
A. N. Baryshev ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.


2021 ◽  
Vol 145 ◽  
pp. 104984
Author(s):  
Christopher R. Richmond ◽  
Laurel L. Ballantyne ◽  
A. Elizabeth de Guzman ◽  
Brian J. Nieman ◽  
Colin D. Funk ◽  
...  

2014 ◽  
Vol 564 ◽  
pp. 27-31 ◽  
Author(s):  
Masahiro Ohsawa ◽  
Junpei Mutoh ◽  
Shohei Yamamoto ◽  
Hiroaki Hisa

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