99mTc annexin V imaging of neonatal hypoxic brain injury
99mTc annexin V imaging of neonatal hypoxic brain injury
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DOI：
10.1161/01.str.31.11.2692
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发表时间：
2000-11-01
期刊：
影响因子：
8.3
通讯作者：
Blankenberg, FG
中科院分区：
文献类型：
--
作者：
D'Arceuil, H;Rhine, W;Blankenberg, FG
背景和目的：-脑缺氧缺血性损伤（HII）后新生儿细胞延迟丢失被认为是脑瘫的主要原因。在这项研究中，我们使用放射性标记的膜联蛋白V（延迟细胞丢失（细胞凋亡）的标记物）对患有HII的新生兔进行成像。方法-22只新生新西兰白兔结扎右颈总动脉，降低吸入氧浓度以诱导I-III。实验动物（n=17）暴露于缺氧环境，直至发生同侧半球平均扩散系数下降。缺氧逆转且平均扩散系数值正常化后，实验动物注射Tc-99m膜联蛋白V。2小时后记录放射性核素图像。结果-实验动物在缺氧后没有显示血脑屏障破坏或灌注异常的MR证据。膜联蛋白图像显示实验动物而非对照动物的两个半球都有多灶性大脑摄取。实验动物大脑的组织学显示，通过末端脱氧核苷酸转移酶介导的 dUTP 缺口标记 (TUNEL) 染色，发现分散的固缩皮质和海马神经元，神经胶质细胞的细胞质空泡化，没有细胞凋亡的证据。细胞类型标记物和外源性膜联蛋白 V 的双重染色显示，在实验大脑和存在完整血脑屏障的对照大脑中，膜联蛋白 V 定位于分散的神经元和星形胶质细胞的细胞质中。 结论：即使在弥散加权和灌注 MR 上显示正常的大脑中，HII 后也可能发生细胞凋亡。这些数据表明放射性标记的膜联蛋白 V 对有脑瘫风险的新生儿进行筛查的作用。
Background and Purpose: -Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII.Methods-Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce I-III. Experimental animals (n=17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred.. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with Tc-99m annexin V. Radionuclide images were recorded 2 hours later.Results-Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier.Conclusions-Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.