ABSTRACT
Transgenic mice have been previously used to assess nerve regeneration following peripheral nerve injury. However, mouse models are limited by their small caliber nerves, short nerve lengths, and their inability to fully participate during behavioral assessments. The transgenic Thy1 GFP rat is a novel transgenic rat model designed to assess regeneration following peripheral nerve injury. However, return of functional and behavioral recovery following nerve injury has not yet been evaluated in these rats. In this study, we ask whether differences in anatomy, recovery of locomotion, myological, and histomorphological measures exist between transgenic Thy1 GFP rats when compared to wild type (WT) Sprague Dawley rats following unilateral sciatic nerve injury. We found that both motor and sensory neuronal architecture, overground and skilled locomotion, muscle force, motor unit number estimation (MUNE) and wet muscle weights, and histomorphometric assessments are similar between both genetic phenotypes. Overall, these data support the use of the transgenic Thy1-GFP rat in experiments assessing functional and behavioral recovery following nerve injury and repair.
Subject(s)
Recovery of Function/physiology , Sciatic Neuropathy/physiopathology , Animals , Axotomy , Disease Models, Animal , Ganglia, Spinal/pathology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Locomotion/physiology , Male , Motor Neurons/pathology , Motor Skills/physiology , Muscle Strength , Muscle, Skeletal/pathology , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Sciatic Neuropathy/pathology , Sensory Receptor Cells/pathology , Spinal Cord/pathology , Stilbamidines , Thy-1 Antigens/geneticsABSTRACT
AIM: Recovery following nerve transection declines when target reconnection is delayed for prolonged periods. GDNF has previously been shown to promote motor axon regeneration following delayed nerve repair. MATERIALS & METHODS: We constructed delivery systems using fibrin gels containing free GDNF or poly(lactide-co-glycolide) microspheres with GDNF. The delivery systems were implanted with fluorescent fibrinogen surrounding the common fibular (CF; peroneal) nerve in transgenic Thy-1 GFP rats (whose axons express GFP) to track degradation of the system. A delayed nerve repair model was designed by transecting the rat CF nerve, where nerve regeneration was prevented by ligating the two stumps to surrounding muscle for 2 months prior to resuture. At resuture, either a delivery system with GDNF or an additional group consisting of fibrin gels with empty microspheres were implanted surrounding the repair site. In an additional positive control, the CF was transected and repaired immediately without delay. RESULTS: ELISA assays demonstrated GDNF release in vitro for 2 weeks from fibrin gels with GDNF microspheres. Implanted delivery systems, including GDNF microspheres, remained surrounding the nerve for at least 10 days compared with 3 days for free GDNF. Four weeks after repair, histomorphometry of distal nerve cross-sections taken 20 mm from the repair site demonstrated increased fiber diameter and myelin thickness due to release of GDNF from microspheres compared with empty microspheres. Additionally, the number of motoneurons that regenerated their axons to the same site increased to comparable levels as immediate repair due to the extended delivery of GDNF from microspheres. CONCLUSION: These findings demonstrate that early measures of nerve regeneration after delayed nerve repair is improved by GDNF microspheres implanted at the coaptation site.
Subject(s)
Axons/pathology , Fibrin/pharmacology , Gels/pharmacology , Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Nerve Regeneration/drug effects , Peroneal Nerve/pathology , Wound Healing/drug effects , Animals , Axons/drug effects , Female , Fluorescent Antibody Technique , Humans , Implants, Experimental , Microspheres , Peroneal Nerve/surgery , Rats , Rats, Sprague-Dawley , Staining and LabelingABSTRACT
BACKGROUND: Brachial plexus injury diagnosed following delivery often causes lifelong disability and frequently results in litigation. While there is no universally accepted name for this condition, the term 'obstetrical brachial plexus palsy' (OBPP) is commonly used worldwide. The difficulty with the term 'OBPP' lies with the use of the word 'obstetrical', which some have construed to imply obstetrical malpractice even if none occurred. Many regions, especially in the United States, are suffering increasing obstetrician shortages, sometimes as a result of unsustainable liability insurance premiums. We wanted to determine whether surgeons felt that an alternative to the term 'OBPP' was more appropriate. METHODS: We surveyed peripheral nerve surgeons worldwide to determine the appropriateness of the term 'OBPP' and alternative terms. RESULTS: The majority of US-based surgeons (94%) preferred alternative terms, such as 'neonatal brachial plexus palsy'. However, only 53% of surgeons from other regions preferred alternative terms. This difference was statistically significant (p < 0.0002). CONCLUSIONS: More precise and descriptive alternatives to the term 'OBPP' are available and acceptable to many surgeons. An alternative to 'OBPP' may improve communication between practitioners, families and the legal system, especially in the United States. Our peripheral nerve organisations may be able to provide further leadership on this matter.
