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三维动脉自旋标记法评估肢体远程缺血预处理后局灶性缺血性脑卒中大鼠模型中脑灌注的改善情况

Three Dimensional-Arterial Spin Labeling Evaluation of Improved Cerebral Perfusion After Limb Remote Ischemic Preconditioning in a Rat Model of Focal Ischemic Stroke.

作者信息

Zheng Tianxiu, Lai Xiaolan, Lu Jiaojiao, Chen Qiuyan, Wei Dingtai

机构信息

Department of Radiology, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, China.

Department of Hematology, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, China.

出版信息

Front Neuroanat. 2022 Jun 30;16:893953. doi: 10.3389/fnana.2022.893953. eCollection 2022.

Abstract

PURPOSE

To investigate the application value of 3D arterial spin labeling (3D-ASL) for evaluating distal limb ischemic preconditioning to improve acute ischemic stroke (AIS) perfusion.

MATERIALS AND METHODS

A total of 40 patients with AISs treated in our hospital from January 2020 to December 2020 were recruited, and 15 healthy individuals who were examined in our hospital during the same period were included as the control group; all of these participants were scored on the National Institutes of Health Stroke Scale (NIHSS) and examined by MRI. Sequences included conventional sequences, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and 3D-ASL, and cerebral infarct volume and cerebral blood flow (CBF) in the area of the infarct lesion were measured. After 3 months of treatment, patients with AIS were scored on the modified Rankin Scale (mRS) and divided into good prognosis and poor prognosis groups. In total, 55 adult male Sprague-Dawley rats were divided randomly into three groups: 20 in the middle cerebral artery occlusion (MCAO) group, 20 in the MCAO + limb remote ischemic preconditioning (LRP) group, and 15 in the sham group. In total, 48 h after the procedures, conventional MRI, DWI, and 3D-ASL sequence data were collected, and 2,3,5-trphenyltetrazolium chloride monohydrate (TTC) staining and behavioral scoring were performed. CBF was recorded in the infarct lesion area and the corresponding contralateral area, and the affected/contralateral relative values (rCBF) were calculated to compare the differences in rCBF between different groups. The pathological changes in brain tissues were observed by HE staining, and the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in brain tissues was detected by immunofluorescence and real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of VEGF was detected by western blotting.

RESULTS

Hypertension and internal carotid atherosclerosis are high-risk factors for ischemic stroke, and CBF values in the infarct area are significantly lower than those in the corresponding areas on the contralateral side. NIHSS and mRS scores and CBF values have higher specificity and sensitivity for the prognosis of patients with AIS. LRP significantly reduces the infarct area, improves behavioral deficits in rats with cerebral ischemia, reduces neurological injury and histological damage, protects vascular structures, and promotes neovascularization. In addition, 3D-ASL showed a significant increase in brain tissue perfusion in the ischemic area after LRP, and the expression of VEGF and CD31 showed a significant positive correlation with CBF values.

CONCLUSION

Three dimensional (3D) ASL can be used to evaluate LRP to improve stroke perfusion, and its protective effect may be closely related to LRP-induced vascular regeneration.

摘要

目的

探讨三维动脉自旋标记(3D-ASL)在评估肢体远端缺血预处理改善急性缺血性脑卒中(AIS)灌注方面的应用价值。

材料与方法

选取2020年1月至2020年12月在我院治疗的40例AIS患者,并纳入同期在我院检查的15名健康个体作为对照组;所有参与者均进行美国国立卫生研究院卒中量表(NIHSS)评分并接受MRI检查。序列包括常规序列、弥散加权成像(DWI)、磁共振血管造影(MRA)和3D-ASL,测量梗死灶区域的脑梗死体积和脑血流量(CBF)。治疗3个月后,对AIS患者进行改良Rankin量表(mRS)评分,并分为预后良好组和预后不良组。将55只成年雄性Sprague-Dawley大鼠随机分为三组:大脑中动脉闭塞(MCAO)组20只、MCAO + 肢体远程缺血预处理(LRP)组20只、假手术组15只。在操作后48小时,收集常规MRI、DWI和3D-ASL序列数据,并进行2,3,5-三苯基氯化四氮唑(TTC)染色和行为评分。记录梗死灶区域及相应对侧区域的CBF,并计算患侧/对侧相对值(rCBF)以比较不同组间rCBF的差异。通过HE染色观察脑组织的病理变化,通过免疫荧光和实时定量聚合酶链反应(RT-qPCR)检测脑组织中血管内皮生长因子(VEGF)和血小板内皮细胞黏附分子-1(PECAM-1/CD31)的表达。通过蛋白质印迹法检测VEGF的蛋白表达。

结果

高血压和颈内动脉粥样硬化是缺血性脑卒中的高危因素,梗死区域的CBF值明显低于对侧相应区域。NIHSS和mRS评分以及CBF值对AIS患者的预后具有较高的特异性和敏感性。LRP显著减小梗死面积,改善脑缺血大鼠的行为缺陷,减轻神经损伤和组织学损伤,保护血管结构并促进新生血管形成。此外,3D-ASL显示LRP后缺血区域脑组织灌注显著增加,VEGF和CD31的表达与CBF值呈显著正相关。

结论

三维(3D)ASL可用于评估LRP改善脑卒中灌注的情况,其保护作用可能与LRP诱导的血管再生密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef89/9280338/2a298a45a28b/fnana-16-893953-g001.jpg

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