دورية أكاديمية
Recovering the regenerative potential in chronically injured nerves by using conditioning electrical stimulation.
| العنوان: | Recovering the regenerative potential in chronically injured nerves by using conditioning electrical stimulation. |
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| المؤلفون: | Senger JB; 1Division of Plastic Surgery, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta., Rabey KN; 2Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta.; 4Department of Anthropology, Faculty of Science, University of Alberta, Edmonton, Alberta, Canada., Acton L; 2Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta., Lin YS; 2Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta., Lingrell S; 2Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta., Chan KM; 3Division of Physical Medicine and Rehabilitation, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta; and., Webber CA; 2Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta. |
| المصدر: | Journal of neurosurgery [J Neurosurg] 2021 Oct 15; Vol. 136 (5), pp. 1442-1454. Date of Electronic Publication: 2021 Oct 15 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Neurological Surgeons Country of Publication: United States NLM ID: 0253357 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1933-0693 (Electronic) Linking ISSN: 00223085 NLM ISO Abbreviation: J Neurosurg Subsets: PubMed not MEDLINE; MEDLINE |
| أسماء مطبوعة: | Publication: Charlottesville, VA : American Association of Neurological Surgeons Original Publication: Chicago [etc.] |
| مستخلص: | Objective: Chronically injured nerves pose a significant clinical challenge despite surgical management. There is no clinically feasible perioperative technique to upregulate a proregenerative environment in a chronic nerve injury. Conditioning electrical stimulation (CES) significantly improves sensorimotor recovery following acute nerve injury to the tibial and common fibular nerves. The authors' objective was to determine if CES could foster a proregenerative environment following chronically injured nerve reconstruction. Methods: The tibial nerve of 60 Sprague Dawley rats was cut, and the proximal ends were inserted into the hamstring muscles to prevent spontaneous reinnervation. Eleven weeks postinjury, these chronically injured animals were randomized, and half were treated with CES proximal to the tibial nerve cut site. Three days later, 24 animals were killed to evaluate the effects of CES on the expression of regeneration-associated genes at the cell body (n = 18) and Schwann cell proliferation (n = 6). In the remaining animals, the tibial nerve defect was reconstructed using a 10-mm isograft. Length of nerve regeneration was assessed 3 weeks postgrafting (n = 16), and functional recovery was evaluated weekly between 7 and 19 weeks of regeneration (n = 20). Results: Three weeks after nerve isograft surgery, tibial nerves treated with CES prior to grafting had a significantly longer length of nerve regeneration (p < 0.01). Von Frey analysis identified improved sensory recovery among animals treated with CES (p < 0.01). Motor reinnervation, assessed by kinetics, kinematics, and skilled motor tasks, showed significant recovery (p < 0.05 to p < 0.001). These findings were supported by immunohistochemical quantification of motor endplate reinnervation (p < 0.05). Mechanisms to support the role of CES in reinvigorating the regenerative response were assessed, and it was demonstrated that CES increased the proliferation of Schwann cells in chronically injured nerves (p < 0.05). Furthermore, CES upregulated regeneration-associated gene expression to increase growth-associated protein-43 (GAP-43), phosphorylated cAMP response element binding protein (pCREB) at the neuronal cell bodies, and upregulated glial fibrillary acidic protein expression in the surrounding satellite glial cells (p < 0.05 to p < 0.001). Conclusions: Regeneration following chronic axotomy is impaired due to downregulation of the proregenerative environment generated following nerve injury. CES delivered to a chronically injured nerve influences the cell body and the nerve to re-upregulate an environment that accelerates axon regeneration, resulting in significant improvements in sensory and motor functional recovery. Percutaneous CES may be a preoperative strategy to significantly improve outcomes for patients undergoing delayed nerve reconstruction. |
| فهرسة مساهمة: | Keywords: chronic nerve injury; conditioning electrical stimulation; nerve reconstruction; peripheral nerve; rat |
| تواريخ الأحداث: | Date Created: 20211015 Latest Revision: 20240521 |
| رمز التحديث: | 20240521 |
| DOI: | 10.3171/2021.4.JNS21398 |
| PMID: | 34653977 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1933-0693 |
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| DOI: | 10.3171/2021.4.JNS21398 |