The back and forth of axonal injury and repair after stroke.
The back and forth of axonal injury and repair after stroke.
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DOI：
10.1097/wco.0000000000000149
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发表时间：
2014-12
影响因子：
4.8
通讯作者：
Hinman JD
中科院分区：
文献类型：
--
作者：
Hinman JD
轴突在中风后的损伤和修复阶段都起着核心作用。本文综述了卒中后轴突损伤研究的新原则以及轴突在卒中后神经修复中的作用。缺血性中风在急性期产生快速和显著的轴突损失。这种轴突的早期损失是由原发性缺血性损伤引起的，其触发钙信号传导波，激活蛋白水解机制和下游信号传导级联。轴突损伤的第二个进行性阶段发生在亚急性期，并损伤在初始缺血性损伤中存活但继续经历部分由轴胶质接触和轴突能量代谢的变化驱动的延迟轴突变性的轴突。从中风中恢复取决于在第三退化/再生阶段期间发生的轴突发芽和重新连接。尽管轴突发挥了重要作用，但对中风后早期和亚急性轴突变性的分子途径了解甚少。轴突神经生物学和信号转导的最新进展表明，新的靶点有望成为潜在的分子治疗方法，包括轴突钙信号转导、轴突胶质细胞能量代谢和细胞粘附以及逆行轴突丝裂原活化蛋白激酶途径。这些新的途径必须适当建模的类型和严重程度的轴突损伤不同中风亚型。中风引起的轴突损伤发生在三个不同的阶段，每个阶段都有一个独特的分子基础。关于轴突内的分子组织和分子信号传导的大量新数据是可用的，但尚未稳健地应用于中风后轴突损伤的研究。确定轴突内有助于损伤和修复的分子通路的时空模式可能为中风的治疗提供新的治疗策略。
The axon plays a central role in both the injury and repair phases after stroke. This review highlights emerging principles in the study of axonal injury in stroke and the role of the axon in neural repair after stroke. Ischemic stroke produces a rapid and significant loss of axons in the acute phase. This early loss of axons results from a primary ischemic injury that triggers a wave of calcium signaling, activating proteolytic mechanisms and downstream signaling cascades. A second progressive phase of axonal injury occurs during the subacute period and damages axons that survive the initial ischemic insult but go on to experience a delayed axonal degeneration driven in part by changes in axoglial contact and axonal energy metabolism. Recovery from stroke is dependent on axonal sprouting and reconnection that occurs during a third degenerative/regenerative phase. Despite this central role played by the axon, comparatively little is understood about the molecular pathways that contribute to early and subacute axonal degeneration after stroke. Recent advances in axonal neurobiology and signaling suggest new targets that hold promise as potential molecular therapeutics including axonal calcium signaling, axoglial energy metabolism and cell adhesion as well as retrograde axonal mitogen-activated protein kinase pathways. These novel pathways must be modeled appropriately as the type and severity of axonal injury vary by stroke subtype. Stroke-induced injury to axons occurs in three distinct phases each with a unique molecular underpinning. A wealth of new data about the molecular organization and molecular signaling within axons is available but not yet robustly applied to the study of axonal injury after stroke. Identifying the spatiotemporal patterning of molecular pathways within the axon that contribute to injury and repair may offer new therapeutic strategies for the treatment of stroke.