シンキ カイハツシタ マンセイ ノウ テイカンリュウ モデル マウス ニ オケル ダイノウ ハクシツ ビョウヘン ト グリア ノ カッセイカ

京都大学0048新制・課程博士博士(医学)甲第11453号医博第2876号新制||医||898(附属図書館)23096UT51-2005-D203京都大学大学院医学研究科脳統御医科学系専攻(主査)教授 大森 治紀, 教授 橋本 信夫, 教授 芹川 忠夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Erythrocyte-Rich Thrombus Is Associated with Reduced Number of Maneuvers and Procedure Time in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy

Background: Only few studies have investigated the relationship between the histopathology of retrieved thrombi and clinical outcomes. This study aimed to evaluate thrombus composition and its association with clinical, laboratory, and neurointerventional findings in patients treated by mechanical thrombectomy due to acute large vessel occlusion. Methods: At our institution, 79 patients were treated by mechanical thrombectomy using a stent retriever and/or aspiration catheter between August 2015 and August 2016. The retrieved thrombi were quantitatively analyzed to quantify red blood cells, white blood cells, and fibrin by area. We divided the patients into two groups – a fibrin-rich group and an erythrocyte-rich group – based on the predominant composition in the thrombus. The groups were compared for imaging, clinical, and neurointerventional data. Results: The retrieved thrombi from 43 patients with acute stroke from internal carotid artery, middle cerebral artery, or basilar artery occlusion were histologically analyzed. Erythrocyte-rich thrombi were present in 18 cases, while fibrin-rich thrombi were present in 25 cases. A cardioembolic etiology was significantly more prevalent among the patients with fibrin-rich thrombi than among those with erythrocyte-rich thrombi. Attenuation of thrombus density as shown on computed tomography images was greater in patients with erythrocyte-rich thrombi than in those with fibrin-rich thrombi. All other clinical and laboratory characteristics remained the same. Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers, shorter procedure times, a shorter time interval between arrival and recanalization, and a higher percentage of stent retrievers in the final recanalization procedure. The occluded vessels did not differ significantly. Conclusions: In this study, erythrocyte-rich thrombus was associated with noncardioembolic etiology, higher thrombus density, and reduced procedure time

Inflammatory Biomarkers in Atherosclerosis: Pentraxin 3 Can Become a Novel Marker of Plaque Vulnerability

<div><p>Inflammation is crucially involved in the development of carotid plaques. We examined the relationship between plaque vulnerability and inflammatory biomarkers using intraoperative blood and tissue specimens. We examined 58 patients with carotid stenosis. Following carotid plaque magnetic resonance imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery (systemic) and common carotid artery immediately before and after CAS (local). Seventeen resected CEA tissue samples were embedded in paraffin, and histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin, adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL-1β, IL-10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were measured by multiplex bead array system and ELISA. CAS-treated patients were classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and TNFα), endothelial activation markers (E-selectin and VCAM-1), and inflammation markers (hs-CRP and PTX3) and downregulation of the anti-inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and intracarotid samples before and after CAS were higher in the vulnerable group than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed in the endothelial and perivascular cells. Our findings reveal that carotid plaque vulnerability is modulated by the upregulation and downregulation of proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a potential predictive marker of plaque vulnerability.</p></div

Proinflammatory and anti-inflammatory biomarkers in vulnerable plaques.

<p>Decreased adiponectin levels induce endothelial cell dysfunction with E-selectin release, with subsequent low IL-10 levels and high TNFα levels. Impaired endothelial cells release E-selectin, PTX3, and TNFα. Macrophages produce PTX3, TNFα, and IL-6.</p

Patient characteristics.

<p>eGFR: Estimated glomerular filtration rate; ACE-I angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker.</p