DDR1 may play a key role in destruction of the blood-brain barrier after cerebral ischemia-reperfusion.

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.

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