Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse-induced median mononeuropathy.
Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse-induced median mononeuropathy.
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DOI：
10.1002/jor.24709
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Popoff SN
中科院分区：
文献类型：
--
作者：
Barbe MF;Hilliard BA;Amin M;Harris MY;Hobson LJ;Cruz GE;Dorotan JT;Paul RW;Klyne DM;Popoff SN
正中神经的包封是过度使用引起的正中单神经病的标志，并导致功能下降。我们测试了针对 CTGF/CCN2 的抗体（称为 FG-3019 或 Pamrevlumab）是否可以在临床相关的过度使用啮齿动物模型（其中出现中位单神经病）中减少已确定的神经纤维化和感觉运动下降。年轻成年雌性大鼠执行为期 18 周的高重复高力 (HRHF) 杠杆拉动任务。然后在 18 周时对大鼠实施安乐死（HRHF 未治疗），或休息并用抗 CCN2 单克隆抗体 (HRHF-Rest/FG-3019) 或 IgG (HRHF-Rest/IgG) 进行全身治疗 6 周，结果与非任务对照大鼠进行比较。与对照组相比，未治疗 HRHF 和 HRHF-Rest/IgG 大鼠的神经病理学表现明显，正中神经中神经周围胶原沉积和髓磷脂碱性蛋白 (dMBP) 降解增加，以及下颈背根神经节 (DRG) 中 P 物质增加。与对照组相比，两组均表现出功能下降，特别是正中神经感觉传导速度下降、有害的低温超敏反应和握力下降。与对照组（没有显示）相比，未经 HRHF 治疗的大鼠腹角神经元中 ATF3 免疫阳性细胞核也有所增加。与对照组相比，FG-3019 治疗的大鼠的正中神经中的神经周围胶原蛋白或 dMBP、下颈部 DRG 中的 P 物质或腹角中的 ATF3 免疫阳性细胞核的水平没有增加到高于对照水平，并且正中神经传导速度和热敏感性相似。我们假设神经纤维化过程通过在运动过程中压迫或阻碍正中神经而导致感觉运动下降，并且使用抗 CCN2 治疗抑制纤维化可以逆转这些影响。
Encapsulation of median nerves is a hallmark of overuse‐induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG‐3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develops. Young adult female rats performed a high repetition high force (HRHF) lever‐pulling task for 18 weeks. Rats were then euthanised at 18 weeks (HRHF untreated), or rested and systemically treated for 6 weeks with either an anti‐CCN2 monoclonal antibody (HRHF‐Rest/FG‐3019) or IgG (HRHF‐Rest/IgG), with results compared with nontask control rats. Neuropathology was evident in HRHF‐untreated and HRHF‐Rest/IgG rats as increased perineural collagen deposition and degraded myelin basic protein (dMBP) in median nerves, and increased substance P in lower cervical dorsal root ganglia (DRG), compared with controls. Both groups showed functional declines, specifically, decreased sensory conduction velocity in median nerves, noxious cold temperature hypersensitivity, and grip strength declines, compared with controls. There were also increases of ATF3‐immunopositive nuclei in ventral horn neurons in HRHF‐untreated rats, compared with controls (which showed none). FG‐3019‐treated rats showed no increase above control levels of perineural collagen or dMBP in median nerves, Substance P in lower cervical DRGs, or ATF3‐immunopositive nuclei in ventral horns, and similar median nerve conduction velocities and thermal sensitivity, compared with controls. We hypothesize that neural fibrotic processes underpin the sensorimotor declines by compressing or impeding median nerves during movement, and that inhibiting fibrosis using an anti‐CCN2 treatment reverses these effects.
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DOI：
10.1016/j.jelekin.2017.10.007
发表时间：
2018-03
期刊：
Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology
影响因子：
--
作者：
Festen-Schrier VJMM;Amadio PC
通讯作者：
Amadio PC
影响因子：
2.8
作者：
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通讯作者：
Amadio, Peter C.
影响因子：
6.2
作者：
Barr, AE;Safadi, FF;Barbe, MF
通讯作者：
Barbe, MF
影响因子：
3.5
作者：
Gonzalez, David;Rebolledo, Daniela L.;Brandan, Enrique
通讯作者：
Brandan, Enrique
影响因子：
4.8
作者：
Hunt D;Raivich G;Anderson PN
通讯作者：
Anderson PN