Parp Inhibition Attenuates Early Brain Injury Through NF-?B/MMP-9 Pathway In A Rat Model Of Subarachnoid Hemorrhage

PurposePoly(ADP-ribose)polymerases(PARPs)play an important role in a range of neurological diseases,however,the role of PARP in early brain injury after SAH remains unclear.This study was designed to explore the role of PARP in early brain injury after SAH and the potential mechanisms..MethodsAn endovascular perforation model was used to induce SAH in rats.Eighty-nine male SD rats were randomly divided into the Sham group,SAH+Vehicle group and SAH+PARP inhibitor(PJ34)group.PJ34(10 mg/kg)or vehicle(0.9%NaCl)were given intraperitoneally at 5 min and 8 h after SAH induction.Mortality,SAH grades,neurological function,Evans Blue extravasation,brain edema,Immunofluorescence Staining and western blot were performed.ResultsPJ34 reduced the BBB permeability and brain edema,improved neurological function and attenuated neuronal cell death in the rat model of SAH.Moreover,PJ34 inhibited the nuclear translocation of NF-?B,decreased expression of proinflammatory cytokines IL-1?,IL-6 and TNF-?,reduced the expression of MMP-9,prevented the degradation of tight junction proteins,and decreased microglia activation.ConclusionPARP inhibition by PJ34 reduced brain edema,microglia activation and neuronal cell death,and improved neurological function in a rat model of SAH.The potential mechanisms might be associated with the NF-?B/MMP-9 pathway.