Abstract
Background
Early brain injury (EBI) is the early phase of secondary complications resulted in poor prognosis of subarachnoid hemorrhage (SAH). GPR18 is a G protein-coupled receptor which has been reported for neuroprotection in ischemia. In this study, we aimed to use resolvin D2 (RvD2) as an agonist to investigate the roles of GPR18 in different brain regions during EBI.
Methods
Location and time course of GPR18 after SAH were measured with immunofluorescence and western blot in endovascular perforation rat model. RvD2 was given one hour intranasally post-SAH, and SAH grades, neurobehavior and brain water content tests were performed after 24 hours. TUNEL and DHE staining were measured 24 hours post-SAH in cortex. Immunofluorescence, western blot and immunohistochemistry of proteins related to EBI in different brain regions were also performed.
Results
We found GPR18 mainly located in meninges, hypothalamus, cortex and white matter. And GPR18 expression increased in meninges and hypothalamus after EBI, however, it decreased in cortex and white matter. RvD2 could improve neurological scores and brain edema. Mast cell degranulation was attenuated, Chymase and Typtase expression decreased after RvD2 administration in meninges. RvD2 attenuated inflammation with increase of POMC, IL-10 and decrease of NPY, TNF-α in hypothalamus. In cortex, RvD2 alleviated oxidative stress and apoptosis, protected blood-brain barrier. RvD2 also ameliorated white matter injury by MBP elevation and APP depression.
Conclusions
Current results emphasized the importance of GPR18 in the whole brain during EBI. Upregulation of GPR18 with RvD2 may improve neurological functions with multi-mechanisms in different brain regions.
3,4-Dihydroxyphenylethanol alleviates early brain injury by modulating oxidative stress and Akt and nuclear factor-κB pathways in a rat model of subarachnoid hemorrhage
