Methylcobalamin Facilitates Collateral Sprouting of Donor Axons and Innervation of Recipient Muscle in End-to-Side Neurorrhaphy in Rats

Abstract

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.

Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis

“…At least, the serum vitamin B12 concentration N 170 ng/mL seemed to be the therapeutic ranges by methylcobalamin treatment in sciatic nerve injury rats [2] and wobbler mice. Previous methylcobalamin-treated mouse studies have not measured the tissue concentration of vitamin B12 [2][3][4][5]. The present study showed that the mean concentration of muscle vitamin B12 was 329.9 ng/g in the high dose group (3 mg/kg/day) and 554.2 in the ultra-high dose group (30 mg/kg/day).…”

“…An important question is how serum and tissue concentrations of vitamin B12 were desired for neuroprotective effects on peripheral neuropathy and denervating muscles. In previous studies of methylcobalamin using animal models of peripheral nerve damages, therapeutic doses were varied from 250 μg/day to 1 mg/kg/day [2][3][4][5]. The mean serum concentration of vitamin B12 was 174.8 ng/mL after subcutaneous administration (1 mg/kg/day) with osmotic minipump [2] and 2500 μg/mL after intraperitoneal administration (500 μg/kg/day) [3].…”

“…has been shown to improve muscle weakness in patients with peripheral neuropathy [1]. Methylcobalamin promotes nerve regeneration in rat peripheral neuropathy or injury models [2][3][4][5]. A previous clinical trial demonstrated short-term high-dose (25 mg/day i.m.)…”

Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury

“…For example, the sciatic nerve injury has been associated to decreased levels of the vitamin B complex and vitamin B12 [ 18 ], indicating that the administration of these vitamins may improve the nerve regeneration process. Moreover, a positive effect of the vitamin B12 on SC proliferation and migration has been shown, including also the myelination of axons after end-to-side neurorrhaphy in rats [ 21 ]. Further on, vitamins B1, B6, and B12, display analgesic effects in experimental animal models for acute and chronic pain, upon the neuronal injury [ 22 ].…”

Vesicular nucleotide transporter‐immunoreactive type I cells associated with P2X3‐immunoreactive nerve endings in the rat carotid body

“…A mouse monoclonal anti‐S100B antibody (clone SH‐B1; S2532, Sigma‐Aldrich, PRID AB_477499) recognized a single band of 11 kDa by immunoblotting in the rat peripheral nerves (Liao, Wang, Huang, & Tseng, ). This antibody has also been used for immunohistochemical analyses of the rat brain (Henriksson & Tjälve, ) and Schwann cells in the peripheral nervous system (Lang et al, ).…”