Division of Neurocritical Care, Massachusetts General Hospital, 55 Fruit Street, Lunder 644, Boston, MA 02114, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Divisions of Stroke, Cerebrovascular and Critical Care Neurology, Brigham and Women's Hospital, Boston, MA, USA.
J Stroke Cerebrovasc Dis. 2022 Oct;31(10):106685. doi: 10.1016/j.jstrokecerebrovasdis.2022.106685. Epub 2022 Aug 22.
Neuroinflammation and secondary injury play a central role in the pathophysiology of intracerebral hemorrhage. The dual endothelin-1/VEGFsignal-peptide receptor (DEspR) has been reported to mediate the inflammatory response after acute brain injury in a rodent model. We performed a pilot study to assess the expression of DEspR on circulating leukocytes in patients who presented with spontaneous intracerebral hemorrhage (ICH).
We performed a prospective observational study of patients presenting to two academic medical centers with ICH. Normal healthy volunteers (NHV) were also recruited for sample analysis. Whole blood was obtained, and flow cytometry was performed to examine DEspR expression on neutrophils, monocytes, and lymphocytes.
A total of 19 patients were included in analysis. Median ICH volume was 39 cm [IQR 19 cm, 73 cm] and median ICH score was 2 [IQR 2, 3]. DEspR expression was more abundant on neutrophils (median 2.4% [IQR 0.5%, 5.8%], p = 0.0064) and monocytes (median 4.4% [IQR 1.7%, 15.8%], p = 0.003) relative to lymphocytes (median 0.9% [IQR 0.2%, 3.3%]). ICH patients had higher DEspR expression in all leukocytes relative to NHV (p < 0.05 for all). Among ICH patients, those with a medical history of hypertension showed higher DEspR expression on neutrophils and monocytes (p = 0.018) compared to those without hypertension.
In this pilot study, DEspR is expressed on circulating neutrophils and monocytes in humans after ICH, with higher levels of expression in those with hypertension. Future work in larger cohorts should examine the relationship of DEspR expression with neuroinflammatory endpoints and long-term outcome.
神经炎症和继发性损伤在脑出血的病理生理学中起着核心作用。双重内皮素 1/VEGF 信号肽受体（DEspR）已被报道在啮齿动物模型中介导急性脑损伤后的炎症反应。我们进行了一项初步研究，以评估在自发性脑出血（ICH）患者中循环白细胞上 DEspR 的表达。
我们对两家学术医疗中心就诊的 ICH 患者进行了前瞻性观察性研究。还招募了正常健康志愿者（NHV）进行样本分析。采集全血，进行流式细胞术检查中性粒细胞、单核细胞和淋巴细胞上 DEspR 的表达。
共纳入 19 例患者进行分析。ICH 体积中位数为 39cm[IQR19cm，73cm]，ICH 评分中位数为 2[IQR2，3]。与淋巴细胞（中位数 0.9%[IQR0.2%，3.3%]）相比，中性粒细胞（中位数 2.4%[IQR0.5%，5.8%]，p=0.0064）和单核细胞（中位数 4.4%[IQR1.7%，15.8%]，p=0.003）上的 DEspR 表达更为丰富。ICH 患者所有白细胞上的 DEspR 表达均高于 NHV（所有 p<0.05）。在 ICH 患者中，与无高血压患者相比，有高血压病史的患者中性粒细胞和单核细胞上的 DEspR 表达更高（p=0.018）。
在这项初步研究中，ICH 后人类循环中性粒细胞和单核细胞上表达了 DEspR，高血压患者的表达水平更高。未来在更大的队列中应检查 DEspR 表达与神经炎症终点和长期结局的关系。
