Navarro X, Vivó Meritxell, Valero-Cabré Antoni
Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain.
Prog Neurobiol. 2007 Jul;82(4):163-201. doi: 10.1016/j.pneurobio.2007.06.005. Epub 2007 Jun 22.
Injuries to the peripheral nerves result in partial or total loss of motor, sensory and autonomic functions conveyed by the lesioned nerves to the denervated segments of the body, due to the interruption of axons continuity, degeneration of nerve fibers distal to the lesion and eventual death of axotomized neurons. Injuries to the peripheral nervous system may thus result in considerable disability. After axotomy, neuronal phenotype switches from a transmitter to a regenerative state, inducing the down- and up-regulation of numerous cellular components as well as the synthesis de novo of some molecules normally not expressed in adult neurons. These changes in gene expression activate and regulate the pathways responsible for neuronal survival and axonal regeneration. Functional deficits caused by nerve injuries can be compensated by three neural mechanisms: the reinnervation of denervated targets by regeneration of injured axons, the reinnervation by collateral branching of undamaged axons, and the remodeling of nervous system circuitry related to the lost functions. Plasticity of central connections may compensate functionally for the lack of specificity in target reinnervation; plasticity in human has, however, limited effects on disturbed sensory localization or fine motor control after injuries, and may even result in maladaptive changes, such as neuropathic pain, hyperreflexia and dystonia. Recent research has uncovered that peripheral nerve injuries induce a concurrent cascade of events, at the systemic, cellular and molecular levels, initiated by the nerve injury and progressing throughout plastic changes at the spinal cord, brainstem relay nuclei, thalamus and brain cortex. Mechanisms for these changes are ubiquitous in central substrates and include neurochemical changes, functional alterations of excitatory and inhibitory connections, atrophy and degeneration of normal substrates, sprouting of new connections, and reorganization of somatosensory and motor maps. An important direction for ongoing research is the development of therapeutic strategies that enhance axonal regeneration, promote selective target reinnervation, but are also able to modulate central nervous system reorganization, amplifying those positive adaptive changes that help to improve functional recovery but also diminishing undesirable consequences.
周围神经损伤会导致运动、感觉和自主神经功能部分或完全丧失，这些功能由受损神经传递至身体的失神经支配节段，这是由于轴突连续性中断、损伤部位远端神经纤维变性以及轴突切断的神经元最终死亡所致。周围神经系统损伤因此可能导致严重残疾。轴突切断后，神经元表型从递质状态转变为再生状态，诱导众多细胞成分的下调和上调以及一些在成年神经元中通常不表达的分子的重新合成。这些基因表达的变化激活并调节负责神经元存活和轴突再生的通路。神经损伤引起的功能缺陷可通过三种神经机制得到补偿：受损轴突再生使失神经支配的靶器官重新获得神经支配、未受损轴突的侧支分支实现重新神经支配以及与丧失功能相关的神经系统回路重塑。中枢连接的可塑性可在功能上补偿靶器官重新神经支配缺乏特异性的情况；然而，人类的可塑性对损伤后感觉定位紊乱或精细运动控制的影响有限，甚至可能导致适应不良的变化，如神经性疼痛、反射亢进和肌张力障碍。最近的研究发现，周围神经损伤会在全身、细胞和分子水平引发一系列并发事件，这些事件由神经损伤引发，并在脊髓、脑干中继核、丘脑和大脑皮层的可塑性变化过程中不断发展。这些变化的机制在中枢基质中普遍存在，包括神经化学变化、兴奋性和抑制性连接的功能改变、正常基质的萎缩和变性、新连接的芽生以及躯体感觉和运动图谱的重组。当前研究的一个重要方向是开发治疗策略，这些策略既能促进轴突再生、促进选择性靶器官重新神经支配，又能调节中枢神经系统重组，放大那些有助于改善功能恢复的积极适应性变化，同时减少不良后果。
