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- Bontioti, Eleana
(författare)
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End-to-side nerve repair - A study in the forelimb of the rat
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nerve injuries have a profound impact on individuals, suffering for the patients and induce cost for society. When dealing with severe nerve injuries that create a gap between nerve segments or when the injury is at the brachial plexus level, the clinical alternatives are limited. The brachial plexus model and its branches in the forelimb was evaluated as an experimental model for studies of nerve regeneration, particularly end-to-side nerve repair. Different types of nerve injuries and repair were induced to the forelimb of the rat, with specific focus on end-to-side nerve repair, i.e. when a distal end of an injured nerve is attached end-to-side to an intact nerve trunk. The radial or both median/ulnar nerves were subjected to a crush injury, a transection and conventional end-to-end nerve repair, a nerve graft procedure or a transection and end-to-side nerve repair. In the latter experiments, the distal nerve segment was attached end-to-side to the intact musculocutaneous nerve. Pawprints and tetanic muscle force were used for evaluation of functional outcome up to eight months after repair. Immunocytochemistry of the C-terminal flanking peptide of NPY (CPON), activating transcription factor 3 (ATF3; marker for cellular activation) and neurofilaments were used to investigate cell body activation and axonal outgrowth. Retrograde labeling detected the source of regenerated nerve fibres. Morphometry analysed the quality of the regenerating axons. Axonal outgrowth was related to the severity of the injury and repair method. A conditioning lesion shortened the time for functional recovery. In end-to-side nerve repair both sensory and motor neurons send axons to the recipient nerve. Retrograde labeling showed few doubled labelled cells indicating that collateral sprouting was only one mechanism by which regeneration occurred. Two recipient nerves could be supported from a single donor nerve. There was no advantage of attachment of also a proximal nerve stump as an extra source of axon to the same donor as an attempt to improve the regenerating capacity. The expression of CPON was dependent on the level of the nerve lesion, i.e. a more profound effect after a proximal injury. Application of an epineural window and/or sutures with or without end-to-side attachment of a nerve segment to a potential donor nerve was needed for ATF3 activation, while application of a piece of muscle or nerve alongside a donor nerve had no such effect. An injury to the donor nerve is a prerequisite for activation of neurons and non-neuronal cells leading to sprouting of axons. End-to-side nerve repair is an alternative method to reconstruct severe nerve injuries when a proximal nerve segment is not available.
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| 2. |
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| 3. |
- Bontioti, Eleana, et al.
(författare)
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End-to-side nerve repair in the upper extremity of rat.
- 2005
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 10:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- The end-to-side nerve-repair technique, i.e., when the distal end of an injured nerve is attached end-to-side to an intact nerve trunk in an attempt to attract nerve fibers by collateral sprouting, has been used clinically. The technique has, however, been questioned. The aim of the present study was to investigate end-to-side repair in the upper extremity of rats with emphasis on functional recovery, source, type, and extent of regenerating fibers. End-to-side repair was used in the upper limb, and the radial or both median/ulnar nerves were attached end-to-side to the musculocutaneous nerve. Pawprints and tetanic muscle force were used to evaluate functional recovery during a 6-month recovery period, and double retrograde labeling was used to detect the source of the regenerated nerve fibers. The pawprints showed that, in end-to-side repair of either one or two recipient nerves, there was a recovery of toe spreading to 60-72% of the preoperative value (lowest value around 47%). Electrical stimulation of the end-to-side attached radial or median/ulnar nerves 6 months after repair resulted in contraction of muscles in the forearm innervated by these nerves (median tetanic muscle force up to 70% of the contralateral side). Retrograde labeling showed that both myelinated (morphometry) sensory and motor axons were recruited to the end-to-side attached nerve and that these axons emerged from the motor and sensory neuronal pool of the brachial plexus. Double retrograde labeling indicated that collateral sprouting was one mechanism by which regeneration occurred. We also found that two recipient nerves could be supported from a single donor nerve. Our results suggest that end-to-side repair may be one alternative to reconstruct a brachial plexus injury when no proximal nerve end is available.
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| 5. |
- Bontioti, Eleana, et al.
(författare)
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Mechanisms underlying the end-to-side nerve regeneration
- 2009
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Ingår i: International Review of Neurobiology. - 0074-7742. ; 87, s. 251-268
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Forskningsöversikt (refereegranskat)abstract
- End-to-side (ETS) nerve repair is used in selected clinical cases. The mechanisms, by which regeneration into the attached nerve segment is initiated and occur, are still not fully understood. Based on numerous experimental studies, different mechanisms have been Suggested by which regenerating axons are recruited, such as contamination From the proximal nerve segment, collateral sprouting, and terminal regenerating sprouting from the donor nerve. A variety of experimental models, most commonly in the lower and upper extremity of rats, and techniques have been used to shed light on the mechanisms. Retrograde labeling techniques have revealed that collateral sprouting do occur, but is probably, at least as observed in long-term experiments, less important over time. Pruning of branching nerve fibers, induced by the collateral sprouting, is an additional mechanism in this context. Experiments have also focused on the stimuli, including the question of epineurial or perineurial windows, that trigger the sprouting of axons form the donor nerve, which can detected by the use of markers of cellular injury. In die present article, we review studies contributing to clarifications of mechanisms of end-to-side nerve repair, including used experimental techniques. We also stress the importance of the plastic brain.
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| 6. |
- Bontioti, Eleana N, et al.
(författare)
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Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries.
- 2003
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 8:3, s. 159-168
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to establish an accurate, reproducible, and simple method to evaluate functional recovery after different types of nerve injuries to the brachial plexus of rats. To that end, pawprints, measured as distance between the first and fourth and second and third digits, were used for evaluation of injuries including crush injury, transection/repair, or graft repair of the median, ulnar, and radial nerves. Immunocytochemistry of the C-terminal flanking peptide of neuropeptide Y (CPON) and neurofilaments was used to investigate the cell body response and axonal outgrowth, respectively. Functional recovery was dependent on the severity as well as on the level of the lesion. Neither a single injury to the median nerve nor an injury to the ulnar nerve affected the pawprint, while an injury to both these nerves or a single injury to the radial nerve caused impairment of pawprints. There was a rapid recovery after crush injury to these nerves compared to previous reports of a similar injury to the sciatic nerve. The pattern of axonal outgrowth was related to the severity of the lesion. A conditioning lesion, i.e., an initial lesion of the same nerve preceding a test injury by a few days, of both motor/sensory fibers led to a quicker functional recovery. Surprisingly, conditioning of only sensory fibers had nearly the same effect. The cell body response was dependent on the level of the nerve lesion. The upper extremity of rats might be useful to evaluate the effects of new repair methods after nerve injuries using functional evaluation with pawprints as a simple and accurate method
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