Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis
Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis
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DOI：
10.1186/s12974-018-1150-4
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发表时间：
2018-04-14
影响因子：
9.3
通讯作者：
Buttari, Fabio
中科院分区：
文献类型：
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作者：
Bassi, Mario Stampanoni;Iezzi, Ennio;Buttari, Fabio
背景：在复发缓解型多发性硬化症（RR-MS）的早期阶段，脑病变负荷与临床残疾之间往往缺乏明确的相关性，从而产生了所谓的临床放射学悖论。不同的因素可能会导致这种差异。特别是，突触可塑性可能会减少脑损伤的临床表现，从而产生持久的突触强度增强，这在很大程度上取决于神经营养素诱导的蛋白质合成。急性炎症期间免疫细胞释放的细胞因子可以改变突触传递和可塑性，可能影响多发性硬化症的临床病程。此外，免疫细胞可以通过分泌参与神经元和少突胶质细胞存活的不同生长因子来促进急性后阶段的大脑修复。血小板源性生长因子 (PDGF) 是一种神经营养因子，可能特别参与临床恢复。事实上，PDGF 在体外和 MS 中促进突触活性的长期增强，因此可能是改善新脑损伤临床补偿的关键因素。本研究的目的是探讨诊断时脑脊液 (CSF) PDGF 浓度是否会影响 RR-MS 的临床病程。方法：在诊断时，我们连续测量了 100 名早期 MS 患者的 CSF 浓度，包括 PDGF、主要促炎和抗炎细胞因子以及神经元损伤的可靠标志物。在随访期间前瞻性收集疾病活动的临床和放射学参数。结果：CSF PDGF 水平与延长无复发生存期呈正相关。相反，疾病活动的放射学标志物、神经元损伤的生化标志物和疾病进展的临床参数不受 PDGF 浓度的影响。较高的脑脊液 PDGF 水平与中枢神经系统内的抗炎环境相关。结论：我们的结果表明，PDGF 可以在 RR-MS 过程中促进更长的无复发期，而不影响炎症再激活和炎症驱动的神经元损伤，并可能增强适应性可塑性。
Background: In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS.Methods: At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro-and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up.Results: CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system.Conclusions: Our results suggest that PDGF could promote a more prolonged relapse-free period during the course of RR-MS, without influencing inflammation reactivation and inflammation-driven neuronal damage and likely enhancing adaptive plasticity.