Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI:10.1177/17562864241243274

Pablo Hervella, Maria Luz Alonso-Alonso, Ana Sampedro-Viana, Manuel Rodríguez-Yáñez, Iria López-Dequidt, José M Pumar, Alberto Ouro, Daniel Romaus-Sanjurjo, Francisco Campos, Tomás Sobrino, José Castillo, Yago Leira, Ramón Iglesias-Rey

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引用次数: 0

Abstract

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies.

Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter.

Design: Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group.

Methods: We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ_1-40, Aβ_1-42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months.

Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ_1-40 and Aβ_1-42 were significantly lower in patients with deep LS (p < 0.0001). Aβ_1-42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001).

Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.

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皮层下和大脑深部小血管疾病的不同血液生物标志物。

背景：脑小血管疾病是腔隙性脑卒中（LS）最常见的病因。了解腔隙性脑卒中的发病机制对于预测疾病的严重程度、预后和开发疗法至关重要：研究将大脑深部结构中的腔隙性脑卒中与皮层下白质中的腔隙性脑卒中区分开来的分子特征：设计：前瞻性病例对照研究，包括 120 名影像学确诊的 LS 患者和 120 名对照组：我们研究了阿尔茨海默病生物标志物[淀粉样β（Aβ1-40，Aβ1-42）]、血清炎症标志物（白细胞介素-6，IL-6）和内皮功能障碍标志物[可溶性肿瘤坏死因子样细胞凋亡弱诱导因子和五肽-3（sTWEAK，PTX3）]与发生在大脑深部结构和皮层下白质的LS之间的关系。此外，我们还研究了 LS、白质高密度（WMHs）和 3 个月后的功能预后之间的联系。不良预后的定义是 3 个月时改良兰金量表>2：结果：深部腔隙性脑梗死患者与近期皮层下小梗死患者的 IL-6、PTX3 和 sTWEAK 水平存在显著差异（20.8 pg/mL 对 15.6 pg/mL，p 对 4624.4 pg/mL，p 对 1660.5 pg/mL，p = 0.001）。与预后良好的患者相比，预后较差的患者在 3 个月时这些生物标志物的浓度明显更高。相比之下，深层 LS 患者的 Aβ1-40 和 Aβ1-42 水平明显较低（皮质下白质 LS 患者的 Aβ1-40 和 Aβ1-42 水平明显较高），而这些患者的预后较差。WMH的严重程度仅与深层LS有显著相关性，并与sTWEAK相关（p 结论：大脑深部结构的腔隙性脑梗塞的病理生理机制似乎与皮层下白质的不同。因此，应探索特定的治疗和预防策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.