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PLoS One. 2013 Sep 30;8(9):e76302. doi: 10.1371/journal.pone.0076302. eCollection 2013.

Methylcobalamin facilitates collateral sprouting of donor axons and innervation of recipient muscle in end-to-side neurorrhaphy in rats.

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Department of Anatomy, Faculty of Medicine, Chung Shan Medical University and Department of Pediatrics, Chung Shan Medical University Hospital, Taichung City, Taiwan.


Using ulnar nerve as donor and musculocutaneous nerve as recipient we found earlier that end-to-side neurorrhaphy resulted in weak functional reinnervation after lengthy survival. End-to-side neurorrhaphy however is the sole choice of nerve repair at times and has the advantage of conserving donor nerve function. Here, we investigated whether myelination-enhancing agent methylcobalamin and motoneuron trophic factor pleiotrophin enhances the recovery after end-to-side neurorrhaphy. Methylcobalamin significantly increased the expression of growth associated protein 43 and S100 protein and βIII tubulin in musculocutaneous nerve 1 month after neurorrhaphy suggesting the ingrowth of ulnar axonal sprouts in reactive Schwann cell environment. Upper limb functional test, compound muscle action potential measurements, motor end plate counts, and axon and myelin analyses showed that methylcobalamin treatment alone or with pleiotrophin improved the recovery significantly, 3 and 6 months post-surgery. There were fewer axons, closer in number to that of the intact recipient nerve, found in the distal repaired nerve of the methylcobalamin-treated than that of the vehicle control, suggesting that methylcobalamin facilitates axonal maturation and eliminates supernumerary sprouts. In conclusion, our results showed that methylcobalamin does indeed enhance the recovery of peripheral nerve repaired in end-to-side configuration.

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