Di Pino Giovanni, Pellegrino Giovanni, Capone Fioravante, Assenza Giovanni, Florio Lucia, Falato Emma, Lotti Fiorenza, Di Lazzaro Vincenzo
Campus Bio-Medico University, Rome, Italy
Campus Bio-Medico University, Rome, Italy McGill University, Montreal, Quebec, Canada.
Neurorehabil Neural Repair. 2016 Jan;30(1):3-8. doi: 10.1177/1545968315583721. Epub 2015 Apr 20.
In search for individualized predictors of stroke recovery, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) is attracting great interest, because it has a negative impact on neurotrophin function. Since stroke recovery relies on brain plastic processes, on which BDNF is permissive, the dominant thought is in favor of a worse recovery in Met carriers. Conversely, we suggest that Met carriers do not differ in terms of absolute ability to recover from stroke, but they do differ on the way they recover. In particular, Met carriers rely more on subcortical plasticity, while ValVal patients more on intracortical plastic processes. Indeed, the direct evidence of impaired Met carrier recovery is inconsistent, as a high worldwide diffusion of the polymorphism suggests. The plasticity taking place in cortex, which is the one targeted by noninvasive brain stimulation strategies aimed at enhancing recovery, is less pronounced in Met carrier stroke patients, who have instead spared global recovery potential. Enhanced subcortical plasticity sustains better stroke recovery of Met carrier mice: this may also happen in humans, explaining the weaker interhemispheric cortical excitability imbalance recently described in Met carriers. Thus, BDNF haplotype determines mechanisms and structures involved in stroke recovery. The less pronounced cortical plasticity of Met carrier implies that plastic changes induced by interventional neurophysiological protocols would be better predictors of ValVal chronic outcome and those protocols would be more effective to boost their recovery. Other strategies, more focused on subcortical mechanisms, should be used in Met carriers.
在寻找中风恢复的个体化预测指标过程中，脑源性神经营养因子（BDNF）的Val66Met多态性引起了极大关注，因为它对神经营养因子功能有负面影响。由于中风恢复依赖于脑可塑性过程，而BDNF对该过程有促进作用，主流观点认为Met携带者的恢复情况较差。相反，我们认为Met携带者从中风恢复的绝对能力并无差异，但恢复方式有所不同。具体而言，Met携带者更多依赖于皮质下可塑性，而ValVal患者更多依赖于皮质内可塑性过程。事实上，正如该多态性在全球范围内的高扩散所表明的那样，关于Met携带者恢复受损的直接证据并不一致。在旨在促进恢复的非侵入性脑刺激策略所针对的皮质中发生的可塑性，在Met携带者中风患者中不太明显，而这些患者的整体恢复潜力并未受损。增强的皮质下可塑性维持了Met携带者小鼠更好的中风恢复：这在人类中也可能发生，解释了最近在Met携带者中描述的较弱的半球间皮质兴奋性失衡。因此，BDNF单倍型决定了中风恢复所涉及的机制和结构。Met携带者皮质可塑性不太明显意味着，介入性神经生理学方案诱导的可塑性变化将是ValVal患者慢性预后的更好预测指标，并且这些方案在促进他们的恢复方面将更有效。对于Met携带者，应采用更侧重于皮质下机制的其他策略。
