Department of Neurology, University of California at San Francisco, San Francisco,CA 94158, USA.
Ann Neurol. 2012 Dec;72(6):961-70. doi: 10.1002/ana.23727.
The scavenger receptor CD36 is injurious in acute experimental focal stroke and neurodegenerative diseases in the adult. We investigated the effects of genetic deletion of CD36 (CD36ko) on acute injury, and oxidative and inflammatory signaling after neonatal stroke.
Postnatal day 9 CD36ko and wild-type (WT) mice were subjected to a transient middle cerebral artery occlusion (MCAO). Injury, phagocytosis of dying cells, and CD36 inflammatory signaling were determined.
While the volume of tissue at risk by diffusion-weighted magnetic resonance imaging during MCAO was similar in neonatal CD36ko and WT mice, by 24 hours after reperfusion, injury was more severe in CD36ko and was associated with increased caspase-3 cleavage and reduced engulfment of neurons expressing cleaved caspase-3 by activated microglia. No significant superoxide generation was observed in activated microglia in injured WT, whereas increased superoxide production in vessels and nuclear factor (NF)-κB activation induced by MCAO were unaffected by lack of CD36. Lyn expression was higher in injured CD36ko, and cell type-specific patterns of Lyn expression were altered; Lyn was expressed in endothelial cells and microglia in WT but predominantly in dying neurons in CD36ko.
Lack of CD36 results in poorer short-term outcome from neonatal focal stroke due to lack of attenuation of NF-κB-mediated inflammation and diminished removal of apoptotic neuronal debris. Although inhibition of CD36 does not seem to be a good therapeutic target for protection after acute neonatal stroke, as it is after adult stroke, seeking better understanding of CD36 signaling in particular cell populations may reveal important therapeutic targets for neonatal stroke.
清道夫受体 CD36 在急性实验性局灶性脑卒中和成人神经退行性疾病中具有损伤作用。我们研究了 CD36 基因缺失（CD36ko）对新生儿脑卒中后的急性损伤、氧化和炎症信号的影响。
对出生后第 9 天的 CD36ko 和野生型（WT）小鼠进行短暂性大脑中动脉闭塞（MCAO）。测定损伤、死亡细胞的吞噬作用和 CD36 炎症信号。
虽然在 MCAO 期间扩散加权磁共振成像的危险组织体积在新生 CD36ko 和 WT 小鼠中相似，但在再灌注后 24 小时，CD36ko 的损伤更严重，与半胱天冬酶-3 切割增加和激活小胶质细胞吞噬表达切割半胱天冬酶-3 的神经元减少有关。在受伤的 WT 中，未观察到激活的小胶质细胞中产生明显的超氧化物，但 MCAO 引起的血管中超氧化物的产生增加和核因子（NF）-κB 的激活不受 CD36 缺乏的影响。在受伤的 CD36ko 中，Lyn 表达更高，并且 Lyn 表达的细胞类型特异性模式发生改变；Lyn 在 WT 中的内皮细胞和小胶质细胞中表达，但在 CD36ko 中主要在死亡神经元中表达。
由于缺乏 NF-κB 介导的炎症的衰减和凋亡神经元碎片清除减少，CD36 缺失导致新生儿局灶性脑卒中的短期预后较差。尽管抑制 CD36 似乎不是急性新生儿脑卒中后保护的一个好的治疗靶点，就像成人脑卒中后一样，但对 CD36 信号在特定细胞群体中的更好理解可能会揭示新生儿脑卒中的重要治疗靶点。
