Brain-derived neurotrophic factor and epilepsy: a systematic review.
Brain-derived neurotrophic factor and epilepsy: a systematic review.
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DOI：
10.1016/j.npep.2018.09.005
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发表时间：
2018-12-01
期刊：
影响因子：
2.9
通讯作者：
Ferrari, Fabrizio
中科院分区：
文献类型：
--
作者：
Iughetti, Lorenzo;Lucaccioni, Laura;Ferrari, Fabrizio
一些体外、离体和体内研究暗示脑源性神经营养因子（BDNF）在癫痫的病理生理学中。我们工作的目的是报告有关BDNF及其在癫痫中的潜在作用的最重要的发现。我们的目标是那些发表在体外和体内的证据BDNF和癫痫之间的关系。基础研究、随机试验、队列研究和综述被考虑用于提供广泛的临床数据。使用作者同意的关键词检索Medline、CENTRAL和Science Direct，直至2017年8月。BDNF在发育和成熟脑中具有明确的作用，在神经元培养物和动物脑切片中具有兴奋作用。此外，BDNF及其结合受体（即原肌球蛋白受体激酶B或Trk B）在癫痫动物模型和人类中增加，特别是在颞叶和海马区。在小鼠脑内急性注射BDNF诱导癫痫发作，阻断其转录和通路几乎或完全消除癫痫发作。相反，BDNF的慢性输注与神经元兴奋性降低相关，可能通过几种机制，包括神经肽Y（NPY）的中枢水平增加，氯离子电导改变和TrkB下调。虽然遗传学研究尚无定论，但血清BDNF在癫痫患者中更常见，并且似乎与疾病的严重程度相关。目前的证据表明，抑制BDNF-TrkB信号传导和加强NPY系统可能是癫痫，特别是颞叶癫痫的潜在治疗策略。
Several in vitro, ex vivo and in vivo studies imply brain-derived neurotrophic factor (BDNF) in the pathophysiology of epilepsy. Aim of our work is to report the most important findings regarding BDNF and its potential role in epilepsy. We targeted those publications addressing both in vitro and in vivo evidences of relationship between BDNF and epilepsy. Basic researches, randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. Medline, CENTRAL, and Science Direct were searched till August 2017 using keywords agreed by the authors. Together with a defined role in developmental and mature brain, BDNF has excitatory effects in neuronal cultures and animal brain slices. Furthermore, both BDNF and its conjugated receptor (i.e. Tropomyosin receptor kinase B or TrkB) are increased in animal models and humans with epilepsy, particularly in the temporal and hippocampal areas. Acute injection of BDNF in brain of mice induces seizures, which are almost or totally abolished blocking its transcription and pathway. Chronic infusion of BDNF is conversely associated with a decreased neuronal excitability, probably via several mechanism including an increase in central levels of neuropeptide Y (NPY), altered conductance of chloride, and downregulation of TrkB. While genetic studies are inconclusive, serum BDNF is more frequently higher in patients with epilepsy and appears to be correlated to severity of disease. Current evidences suggest that inhibiting BDNF-TrkB signaling and reinforcing the NPY system could represent a potential therapeutic strategy for epilepsy, especially for temporal lobe epilepsy.