title: DDR1 may play a key role in destruction of the blood-brain barrier after cerebral ischemia-reperfusion.
abstract: Discoidin domain receptor 1 (DDR1) has been shown to mediate matrix metalloproteinase-9 (MMP-9) secretions and degrade all extracellular matrix compounds in mammalian tumor cells. We hypothesized that DDR1 expression will be elevated and the blood-brain barrier (BBB) will be damaged after focal cerebral ischemia in rats. Inhibiting DDR1 expression can alleviate BBB disruption and cerebral ischemic damage via down-regulation of MMP-9 expression and activity. To test our hypothesis, we injected specific DDR1 siRNA into ipsilateral ischemic lateral ventricles in a focal ischemic model. Our results showed that phospho-DDR1 expression increased after ischemia/reperfusion (I/R) injury (p < 0.01). Inactivation of DDR1 by specific siRNA caused a decrease in phospho-DDR1 and MMP-9 expression in the ischemic cortex, reduced stroke-induced infarct volume, and alleviated BBB disruption in rat brain following I/R injury (p < 0.01). Our results suggested that DDR1-siRNA attenuates phospho-DDR1 and MMP-9 upregulation, which was followed by a reduction in infarction and BBB disruption in the ischemic brain after I/R injury. DDR1 may represent a molecular target for the prevention of BBB disruption after cerebral I/R injury.
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Mingxia
authors: M
authors: Zhu
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Dong
authors: D
authors: Xing
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Zhihong
authors: Z
authors: Lu
authors: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Yanhong
authors: Y
authors: Fan
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Wugang
authors: W
authors: Hou
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors: Hailong
authors: H
authors: Dong
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: mzkxlz@126.com.
authors: Lize
authors: L
authors: Xiong
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: dongh369@126.com.
authors: Hui
authors: H
authors: Dong
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology*; D001921:Brain / Q000201:enzymology; D002545:Brain Ischemia / Q000201:enzymology*; D000070819:Discoidin Domain Receptor 1; D057967:Infusions, Intraventricular; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015427:Reperfusion Injury / Q000201:enzymology
chemical_list: D034741:RNA, Small Interfering; C511169:DDR1 protein, rat; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D020780:Matrix Metalloproteinase 9
keywords: Blood–brain barrier; Discoidin domain receptor 1; MCAO; Matrix metalloproteinase; Rats