1Department of Neurosurgery, University Hospital Essen, University Duisburg-Essen.
2Institute for Neuropathology, University Hospital Essen, University Duisburg-Essen; and.
Neurosurg Focus. 2022 Jul;53(1):E3. doi: 10.3171/2022.4.FOCUS2210.
The pathophysiology of development, growth, and rupture of arteriovenous malformations (AVMs) is only partially understood. However, inflammation is known to play an essential role in many vascular diseases. This feasibility study was conducted to investigate the expression of enzymes (cyclooxygenase 2 [COX-2] and NLRP3 [NOD-, LRR-, and pyrin domain-containing protein 3]) in the AVM nidus that are essential in their inflammatory pathways and to explore how these influence the pathophysiology of AVMs.
The study group comprised 21 patients with partially thrombosed AVMs. The cohort included 8 ruptured and 13 unruptured AVMs, which had all been treated microsurgically. The formaldehyde-fixed and paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 and NLRP3 (COX-2 clone: CX-294; NLRP3: ab214185). The authors correlated MRI and clinical data with immunohistochemistry, using the Trainable Weka Segmentation algorithm for analysis.
The median AVM volume was 2240 mm3. The proportion of NLRP3-positive cells was significantly higher (26.23%-83.95%), compared to COX-2 positive cells (0.25%-14.94%, p < 0.0001). Ruptured AVMs had no higher expression of NLRP3 (p = 0.39) or COX-2 (p = 0.44), compared to nonruptured AVMs. Moreover, no patient characteristics could be reported that showed significant correlations to the enzyme expression.
NLRP3 consistently showed an approximately 10-fold higher expression level than COX-2, making the inflammatory process in AVMs appear to be mainly associated with ischemic (NLRP3)-driven rather than with mechanical (COX-2)-driven inflammatory pathways. No direct associations between NLRP3 and COX-2 expression and radiological, standard histopathological, or patient characteristics were found in this cohort.
动静脉畸形（AVM）的发生、生长和破裂的病理生理学机制尚不完全清楚。然而，炎症被认为在许多血管疾病中起着至关重要的作用。本可行性研究旨在探讨AVM 病灶中炎症途径中必需的酶（环氧化酶 2 [COX-2]和 NLRP3 [NOD、LRR 和 pyrin 结构域蛋白 3]）的表达，并探索这些酶如何影响 AVM 的病理生理学。
研究组包括 21 例部分血栓形成的 AVM 患者。该队列包括 8 例破裂和 13 例未破裂的 AVM，均经显微手术治疗。使用针对 COX-2 和 NLRP3 的单克隆抗体（COX-2 克隆：CX-294；NLRP3：ab214185）对福尔马林固定和石蜡包埋的样本进行免疫组织化学染色。作者使用 Trainable Weka Segmentation 算法对 MRI 和临床数据与免疫组织化学进行了相关性分析。
AVM 的中位数体积为 2240mm3。与 COX-2 阳性细胞（0.25%-14.94%，p<0.0001）相比，NLRP3 阳性细胞的比例明显更高（26.23%-83.95%）。与未破裂的 AVM 相比，破裂的 AVM 中 NLRP3（p=0.39）或 COX-2（p=0.44）的表达没有更高。此外，没有患者特征与酶表达呈显著相关。
NLRP3 的表达水平始终比 COX-2 高约 10 倍，这表明 AVM 中的炎症过程主要与缺血（NLRP3）驱动的炎症途径相关，而不是与机械（COX-2）驱动的炎症途径相关。在本队列中，未发现 NLRP3 和 COX-2 表达与影像学、标准组织病理学或患者特征之间存在直接关联。
