Activity-Based Therapies for Repair of the Corticospinal System Injured during Development.
Activity-Based Therapies for Repair of the Corticospinal System Injured during Development.
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DOI：
10.3389/fneur.2014.00229
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发表时间：
2014
影响因子：
3.4
通讯作者：
Martin JH
中科院分区：
文献类型：
--
作者：
Friel KM;Williams PT;Serradj N;Chakrabarty S;Martin JH
这篇综述介绍了皮质脊髓束（CST）发育的机制基础，来源于动物模型，并应用已经学到的知识来告知基于神经活动的CST修复策略。我们首先讨论了在正常发育中，早期的双侧CST投影后来被细化为密集的交叉CST投影，同时保持稀疏的同侧投影。利用一种新的小鼠遗传模型，我们发现促进同侧CST投射会产生镜像运动，这在偏瘫性脑瘫（CP）中很常见，这表明当同侧CST投射变得异常密集和强烈时，它们就会变得不适应。接下来，我们将讨论动物研究如何支持一种发展的“竞争规则”，即更活跃/使用的连接更具竞争力，并超过较少活跃/使用的连接。基于这一规律，单侧损伤后受损的CST与未损伤的CST相比，竞争脊髓突触连接的能力更弱。这可能导致受损半球对侧投影的逐渐丧失和未受损半球同侧CST的反应性增加。损伤后发展中的CST的病理生理学知识为介入策略提供了依据。在偏瘫CP的动物模型中，促进受损系统的活性或在发育性损伤后立即降低未受损系统的活性，都能增加受损系统的突触竞争力，有助于显著的CST修复和运动恢复。然而，延迟干预，尽管显著的CST修复，不能恢复熟练的运动，强调需要考虑其他神经系统的修复策略，包括红脊髓和脊髓间神经系统。我们的介入方法利用神经活动依赖过程，在恢复功能方面非常有效。这些方法是微创的，并准备翻译到人类。
This review presents the mechanistic underpinnings of corticospinal tract (CST) development, derived from animal models, and applies what has been learned to inform neural activity-based strategies for CST repair. We first discuss that, in normal development, early bilateral CST projections are later refined into a dense crossed CST projection, with maintenance of sparse ipsilateral projections. Using a novel mouse genetic model, we show that promoting the ipsilateral CST projection produces mirror movements, common in hemiplegic cerebral palsy (CP), suggesting that ipsilateral CST projections become maladaptive when they become abnormally dense and strong. We next discuss how animal studies support a developmental “competition rule” whereby more active/used connections are more competitive and overtake less active/used connections. Based on this rule, after unilateral injury the damaged CST is less able to compete for spinal synaptic connections than the uninjured CST. This can lead to a progressive loss of the injured hemisphere’s contralateral projection and a reactive gain of the undamaged hemisphere’s ipsilateral CST. Knowledge of the pathophysiology of the developing CST after injury informs interventional strategies. In an animal model of hemiplegic CP, promoting injured system activity or decreasing the uninjured system’s activity immediately after the period of a developmental injury both increase the synaptic competitiveness of the damaged system, contributing to significant CST repair and motor recovery. However, delayed intervention, despite significant CST repair, fails to restore skilled movements, stressing the need to consider repair strategies for other neural systems, including the rubrospinal and spinal interneuronal systems. Our interventional approaches harness neural activity-dependent processes and are highly effective in restoring function. These approaches are minimally invasive and are poised for translation to the human.
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影响因子：
2.2
作者：
Al-Oraibi, Saleh;Eliasson, Ann-Christin
通讯作者：
Eliasson, Ann-Christin
影响因子：
5.3
作者：
Brus-Ramer, Marcel;Carmel, Jason B.;Martin, John H.
通讯作者：
Martin, John H.
影响因子：
2
作者：
Ellis, Michael D.;Acosta, Ana Maria;Dewald, Julius P. A.
通讯作者：
Dewald, Julius P. A.
DOI：
10.1523/jneurosci.1435-10.2010
发表时间：
2010-08-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Carmel JB;Berrol LJ;Brus-Ramer M;Martin JH
通讯作者：
Martin JH
影响因子：
3
作者：
Deppe, Wolfgang;Thuemmler, Kerstin;Wiedemann, Baerbel
通讯作者：
Wiedemann, Baerbel