Abstract:
:Lysophosphatidic acid (LPA) the simplest of the water-soluble phospholipids, is produced by activated platelets, macrophage and endothelial cells. It also evokes various biological responses. When LPA concentrations reach high levels, brain injury, including stroke and intracerebral hemorrhage (ICH), occurs. Previous studies have shown that LPA is crucial in increasing blood-brain barrier (BBB) permeability, and the Rho/Rho kinase (ROCK) signaling pathway is involved in the regulation of endothelial permeability. However, the exact mechanism by which the Rho/ROCK pathway mediates BBB disruption induced by LPA remains to be determined. In the present study, we observed that LPA induced the increase of BBB permeability in the right striatum after 10 µl LPA (100 µM) was injected into the ipsilateral caudate nucleus of rats. The ROCK was involved in the expression of proteolytic enzymes, matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA), leading to LPA-induced BBB disruption. ROCK inhibitor (Y27632) markedly inhibited the expression of proteolytic enzymes induced by LPA as well as the BBB disruption after it was co-injected with LPA. Thus, results of the present study suggest that LPA increases BBB permeability, which may be due to the Rho/ROCK signaling pathway and the subsequent production of proteolytic enzymes MMP-9 and uPA.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Yu Y,Qin J,Liu M,Ruan Q,Li Y,Zhang Zdoi
10.3892/ijmm.2014.1618subject
Has Abstractpub_date
2014-03-01 00:00:00pages
661-9issue
3eissn
1107-3756issn
1791-244Xjournal_volume
33pub_type
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