Biphasic bisperoxovanadium administration and Schwann cell transplantation for repair after cervical contusive spinal cord injury.

Biphasic bisperoxovanadium administration and Schwann cell transplantation for repair after cervical contusive spinal cord injury.
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DOI:
10.1016/j.expneurol.2014.12.002
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发表时间:
2015-02
影响因子:
5.3
通讯作者:
Xu, Xiao-Ming
Xu, Xiao-Ming
中科院分区:
医学2区
文献类型:
--
作者:
Walker, Chandler L.;Wang, Xiaofei;Bullis, Carli;Liu, Nai-Kui;Lu, Qingbo;Fry, Colin;Deng, Lingxiao;Xu, Xiao-Ming

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雪旺细胞(SC)有望用于脊髓损伤(SCI)修复;然而,作为单独治疗存在局限性。我们发现双过氧钒(bpV)对磷酸酶和张力蛋白同源物(PTEN)的急性抑制具有神经保护作用,并增强了颈部半挫伤SCI后的功能。我们假设联合急性bpV治疗和延迟SC植入将进一步改善颈脊髓损伤后的神经保护和恢复。将成年雌性Sprague道利(SD)大鼠随机分为5组:假手术组、溶媒组、bpV组、SC移植组和bpV + SC移植组。从表达绿色荧光蛋白(GFP)的成年SD大鼠(GFP-SC)中分离SC。200 g/kg bpV(pic)腹腔内(i. p.)在bpV治疗组中,SCI后每天两次,持续7天。于伤后第8天将GFP-SCs(1 × 106/5 μl培养基)移植于损伤中心。前肢功能测试10周,并进行组织学评估。与单独损伤相比,单独bpV显著减少损伤(40%,p<0.05)和空化(65%,p<0.05),并改善功能恢复(p <0.05)。该组合促进了类似的神经保护(p<0.01,相对于损伤);然而,单独的GFP-SC没有。两个SC移植组均表现出显著的长期SC存活、SMI-31+轴突长入和SC移植物中存在的RECA-1+血管;然而,bpV + SC促进的轴突-病变比仅SC高89%。我们的结论是,bpV可能在很大程度上有助于神经保护和功能的好处,而SC促进相当多的宿主组织的相互作用和修改。两者的结合显示出作为促进SCI后恢复的有吸引力的策略的前景。
Schwann cells (SCs) hold promise for spinal cord injury (SCI) repair; however, there are limitations for use as a lone treatment. We showed acute inhibition of the phosphatase and tensin homologue (PTEN) by bisperoxovanadium (bpV) was neuroprotective and enhanced function following cervical hemicontusion SCI. We hypothesized that combining acute bpV therapy and delayed SC engraftment would further improve neuroprotection and recovery after cervical SCI. Adult female Sprague Dawley (SD) rats were randomly sorted into 5 groups: sham, vehicle, bpV, SC transplantation, and bpV + SC transplantation. SCs were isolated from adult green fluorescent protein (GFP)-expressing SD rats (GFP-SCs). 200 g/kg bpV(pic) was administered intraperitoneally (i.p.) twice daily for 7 days post-SCI in bpV-treated groups. GFP-SCs (1 × 106 in 5 μl medium) were transplanted into the lesion epicenter at the 8th day post-SCI. Forelimb function was tested for 10 weeks and histology was assessed. bpV alone significantly reduced lesion (by 40%, p<0.05) and cavitation (by 65%, p<0.05) and improved functional recovery (p <0.05) compared to injury alone. The combination promoted similar neuroprotection (p<0.01 vs. injury); however, GFP-SCs alone did not. Both SC-transplanted groups exhibited remarkable long-term SC survival, SMI-31+ axon ingrowth and RECA-1+ vasculature presence in the SC graft; however, bpV + SCs promoted an 89% greater axon-to-lesion ratio than SCs only. We concluded that bpV likely contributed largely to the neuroprotective and functional benefits while SCs facilitated considerable host-tissue interaction and modification. The combination of the two shows promise as an attractive strategy to enhance recovery after SCI.
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