Abstract: BACKGROUND: End-to-side nerve repair is attachment of a single distal nerve segment (recipient nerve) end-to-side to an intact donor nerve when there is a lack of proximal nerve segment after injury. The technique is currently used clinically but the mechanism(s) behind this technique are essentially unknown. METHODS: We have studied end-to-side nerve repair in the forelimb of rats, where a single distal radial nerve or an ulnar or a median, or both, nerves are attached end-to-side to an intact musculocutaneous nerve. We have studied functional recovery, origin of the regenerating axons and cell activation by the end-to-side nerve repair. FINDINGS: Functional recovery occurs after end-to-side nerve repair but is less sufficient than conventional end-to-end nerve repair or a nerve graft procedure. Sensory and motor axons grow from the musculocutaneous nerve out into the attached nerve segment(s). An injury is required to the musculocutaneous nerve to activate sensory and motor neurons as well as Schwann cells in the musculocutaneous nerve for initiation of regeneration. CONCLUSIONS: End-to-side nerve repair may be an alternative method in specific cases of complex nerve injuries to reconstruct nerve trunks when no other repair options are possible. Some functional recovery does occur but regeneration of sensory and motor axons require an injury to the neurons of the donor nerve.
Abstract: Regeneration occurs if a distal nerve segment is attached end-to-side to an intact donor nerve after the nerve has been injured. We investigated if attachment of a proximal nerve segment as well, as an extra source of axons, had any advantage over the single attachment of a distal nerve segment to the same donor nerve. In rats, a single distal radial nerve, or both the proximal and distal radial nerve segments, were attached end-to-side to the musculocutaneous nerve, and effects were examined up to eight months after the repair. Cell profiles were double-labelled, indicating recruitment of axons by collateral sprouting, but there were few such cells. There was a shift in the distribution of retrograde labelled neuronal cell profiles in spinal cord and in DRGs between the two types of repair. Both procedures resulted in axonal outgrowth and some functional recovery, but there was no improvement if a proximal nerve segment was also used as a source for axons.
Abstract: We wanted to find out if any of three different types of manipulations: a piece of muscle or nerve put parallel to a nerve; an epineurial window made, or sutures inserted into a nerve, or both; or pieces of nerve sutured to an epineurial window end-to-side to the musculocutaneous or sciatic nerve, resulted in activation of activating transcription factor 3 (ATF3) in neurons and in non-neuronal cells. ATF3, a marker of cell activation, was investigated by immunocytochemistry one week after manipulation. A piece of nerve or muscle parallel to a nerve did not induce ATF3 locally in the nerve and induced ATF3 only rarely in neurons. In contrast, an epineurial window or insertion of sutures, or both, with or without attachment of a piece of nerve placed end-to-side, induced robust ATF3 expression. We conclude that an injury to a peripheral nerve trunk associated with end-to-side nerve repair, activates neurons and non-neuronal cells and may contribute to sprouting of axons into the nerve attached end-to-side.
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.
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.
Abstract: The purpose of this study was to investigate the feasibility of rapid intraoperative elongation of the rat sciatic nerve with the use of tissue expander and to assess its functional recovery. Out of 51 rats 43 had their right sciatic nerve expanded with a 5-ml intraoperative expander over 1 hr and 8 were sham-operated controls. The functional recovery of the nerve was assessed at intervals up to 4 months using the Sciatic Functional index (SFI), neurophysiological indices, and histology. Intraoperative expansion elongated the rat sciatic nerve by about 13%. SFI decreased on the first postoperative day and started to recover by Day 7, reaching almost preoperative values by Days 14 and 30 according to De Medinaceli and Bain-Mackinnon-Hunter formulas, respectively. Latency and motor conduction velocity demonstrated a deterioration after expansion which peaked on Day 1. Recovery started by Day 7 and reached preoperative levels by 60 days. The histological findings indicated minor aberrations immediately after expansion and maximal demyelination with minimal axonal disruption on Day 1. The reparative process started by Day 7 and continued till Day 120 when almost no histological changes were observed. In conclusion, intraoperative nerve expansion successfully elongates the rat sciatic nerve. It also causes functional and morphological abnormalities which are of low to moderate degree, have a short duration, and are reversible. Intraoperative nerve expansion might be a valuable solution in the treatment of short nerve gaps, but its clinical application still needs to be evaluated.
