Berberine Enhanced Survival and Axonal Regenration of Motoneurons Following Spinal Root Avulsion and Reimplantation in Rats
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AbstractBackground and Aims: Brachial plexus avulsion (BPA) refers to tearing off of the root from the surface of the spinal cord, which could induce the death of most motoneurons and degeneration of axons in the corresponding spinal segment, thus resulting in permanent paralysis of motor functions in the upper limb. There is currently no satisfactory treatment for BPA and its clinical prognosis is poor. Besides, BPA triggers an intense local inflammation response and oxidative stress, leading to apoptosis in neurons and glia. Berberine (BBR), an isoquinoline alkaloid, is the major active compound found in Phellodendron chinense Schneid. Growing evidence suggests that BBR has neuro-protective, anti-inflammatory and anti-oxidative properties in various animal models of central nervous system (CNS)-related disorders [4]. In recent years, the protective effect of BBR on the neurodegenerative disorders has been increasingly concerned. Here, we investigated whether BBR could promote motoneuron survival and axonal regeneration in a rat model of BPA.
Methods: Adult female Sprague Dawley rats (180-220 g) were orally administered with berberine (60, 120 and 240 mg/kg) after avulsion-replantation injury. Terzis grooming test (TGT) was performed weekly to evaluate the motor functional recovery of the injured upper limb. The regeneration of motoneurons was checked by FluoroGold (FG) retrograde labeling. At 1, 2, 4 and 8 weeks after injury, we employed immunofluorescence to detect positive cells of nNOS, ChAT, CISD2, P75, GFAP and IBA1 in C5-C7 spinal cord tissues. Besides, biceps were stained with H&E, α-Bungarotoxin (α-BTX) and NF-200 for motor endplate assessment, the numbers of ChAT and GAP43 positive fibers were counted in musculocutaneous nerve. Meanwhile, the expressions of SOD, Akt, and NF-κB were determined by western blot.
Results: Our results showed that BBR obviously enhanced survival of motoneurons and accelerated the recovery of motor function in the forelimb following root avulsion and reimplantation. The number of FG-labeled and P75+ regenerative motoneurons was significantly elevated in BBR treatment animals. The survival of motoneurons was notably promoted with BBR administration through increasing the ChAT-positive and CISD2-positive cells and decreasing nNOS-positive cells. Moreover, reduced muscle atrophy, increased functional endplates and motor axons in biceps and musculocutaneous nerve were observed in BBR-treated rats. Besides, BBR markedly reduced microglia and astrocyte activation, up-regulated the expressions of Cu/Zn SOD and Akt and down-regulated the expression of NF-κB.
Conclusions: These results suggested that berberine could be used to assist reimplantation surgery in repairing BPA injuries in clinical treatment, may be through Akt signaling activation and downregulation of NF-κB nuclear transposition.
All Author(s) ListXie ZHANG, Xiao Dong LIU, Qiuju YUAN, Zhixiu LIN
Name of ConferenceInternational Conference on Brain Research in Chinese Medicine: Degeneration and Repair
Start Date of Conference26/07/2018
End Date of Conference28/07/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Proceedings TitleInternational Conference on Brain Research in Chinese Medicine: Degeneration and Repair
Year2018
Month7
LanguagesEnglish-United Kingdom

Last updated on 2019-24-10 at 11:08