Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics.
Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics.
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DOI：
10.1371/journal.pone.0111072
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Karimi-Abdolrezaee S
中科院分区：
文献类型：
--
作者：
Alluin O;Delivet-Mongrain H;Gauthier MK;Fehlings MG;Rossignol S;Karimi-Abdolrezaee S
虽然已经在动物模型中评估了脊髓损伤（SCI）后的几种细胞和药理学治疗，但越来越多的人认识到解决胶质瘢痕的方法，包括使用软骨素酶ABC（ChABC），可以促进神经解剖学可塑性。此外，越来越多的证据表明，组合策略是解锁ChABC所能实现的可塑性的关键。鉴于此，我们评估了ChABC在组合方法中的解剖学和功能后果，该方法还包括生长因子（EGF，FGF 2和PDGF-AA）治疗和每日跑步机训练对中胸夹压SCI大鼠后肢运动恢复的影响。使用定量的神经解剖学和运动学评估，我们证明了联合治疗显着增强了主要下行脊髓束，如皮质脊髓和神经能脊髓通路的神经解剖可塑性。此外，药物治疗减弱了慢性星形胶质细胞增生和炎症病变处和附近的跑步机训练的适度协同作用。我们还观察到一种趋势，即在SCI后的前4周内，用ChABC和生长因子治疗的大鼠的运动能力较早恢复，并伴有整体角度偏移的改善。在7周恢复期结束时，所有组的大鼠在跑步机上运动期间表现出令人印象深刻的运动学参数的自发恢复。然而，虽然组合治疗导致明确的慢性神经解剖可塑性，这些结构变化并没有转化为一个额外的长期改善运动参数的研究，包括后肢-前肢耦合。这些研究结果表明，联合ChABC，生长因子和运动训练对损伤脊髓的可塑性和诱导早期神经行为恢复的潜力的有益影响。然而，可能需要额外的方法，如干细胞疗法或更适应的跑步机训练方案来优化这种修复策略，以诱导持续的功能性运动改善。
While several cellular and pharmacological treatments have been evaluated following spinal cord injury (SCI) in animal models, it is increasingly recognized that approaches to address the glial scar, including the use of chondroitinase ABC (ChABC), can facilitate neuroanatomical plasticity. Moreover, increasing evidence suggests that combinatorial strategies are key to unlocking the plasticity that is enabled by ChABC. Given this, we evaluated the anatomical and functional consequences of ChABC in a combinatorial approach that also included growth factor (EGF, FGF2 and PDGF-AA) treatments and daily treadmill training on the recovery of hindlimb locomotion in rats with mid thoracic clip compression SCI. Using quantitative neuroanatomical and kinematic assessments, we demonstrate that the combined therapy significantly enhanced the neuroanatomical plasticity of major descending spinal tracts such as corticospinal and serotonergic-spinal pathways. Additionally, the pharmacological treatment attenuated chronic astrogliosis and inflammation at and adjacent to the lesion with the modest synergistic effects of treadmill training. We also observed a trend for earlier recovery of locomotion accompanied by an improvement of the overall angular excursions in rats treated with ChABC and growth factors in the first 4 weeks after SCI. At the end of the 7-week recovery period, rats from all groups exhibited an impressive spontaneous recovery of the kinematic parameters during locomotion on treadmill. However, although the combinatorial treatment led to clear chronic neuroanatomical plasticity, these structural changes did not translate to an additional long-term improvement of locomotor parameters studied including hindlimb-forelimb coupling. These findings demonstrate the beneficial effects of combined ChABC, growth factors and locomotor training on the plasticity of the injured spinal cord and the potential to induce earlier neurobehavioral recovery. However, additional approaches such as stem cell therapies or a more adapted treadmill training protocol may be required to optimize this repair strategy in order to induce sustained functional locomotor improvement.
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DOI：
10.1523/jneurosci.2995-12.2012
发表时间：
2012-09-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Husch A;Van Patten GN;Hong DN;Scaperotti MM;Cramer N;Harris-Warrick RM
通讯作者：
Harris-Warrick RM
影响因子：
2.7
作者：
Fouad, K;Metz, GAS;Schwab, ME
通讯作者：
Schwab, ME
影响因子：
2.5
作者：
Barriere, Gregory;Frigon, Alain;Rossignol, Serge
通讯作者：
Rossignol, Serge
影响因子：
2.2
作者：
Fouad, K.;Pearse, D. D.;Vavrek, R.
通讯作者：
Vavrek, R.
软骨素酶ABC促进脊髓损伤后完整和受伤的脊柱系统的发芽。
DOI：
10.1523/jneurosci.2980-06.2006
发表时间：
2006-10-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barritt AW;Davies M;Marchand F;Hartley R;Grist J;Yip P;McMahon SB;Bradbury EJ
通讯作者：
Bradbury EJ