Mechanism Of PPARβand MMP-9Involved In Early Brain Injury After Experimental Subarachnoid Hemorrhage

ObjectiveTo investigate the mechanism of early brain injury after SAH in ratsby observing the expression of PPARβ, NF-κB and MMP-9, and theapoptosis of neurons in hippocampus in early phase after SAH, andpermeability of BBB and BWC.Methods1. Simulation of SAH model: SAH animals were injected intosuprachiasmatic cistern with arterial blood.2. Expression of PPARβ, NF-κB and MMP-9mRNA were examinedby Real-time PCR. Expression of PPARβ, NF-κB and MMP-9protein wereexamined by immunohistochemistry and western blot.3. Observing the apoptosis of neurons by TUNEL staining inhippocampus.4. BBB permeability and the brain edema were examined bymeasuring brain EB contents and BWC in rats.5. The specific PPARβ agonist GW0742was used to increase the expression of PPARβ, and the relationship among the expression of PPARβ,NF-κB and MMP-9, apoptosis, BBB and brain edema were observed. Theneuroprotection of GW0742to EBI was also observed.Results1. The expressions of protein and mRNA of PPARβ decreaseddramatically at6h and reached to the lowest at72h (P<0.05); theexpressions of NF-κB increased significantly at6h and reached the highestat72h (P<0.05); the expressions of MMP-9increased significantly at6hand reached the highest at72h (P<0.05).2. The examination of TUNEL suggested that compared to shamgroup, the number of neuronal apoptosis of hippocampus increaseddramatically at6h after SAH, reached to the peak at72h (P<0.05).3. Compared to sham group, the brain EB contents and BWC weredramatically increased at6h and reached the peak at72h (P<0.05).4. The expression of PPARβ was increased dramatically by GW0742at72h after SAH, meanwhile the expressions of NF-κB and MMP-9decreased. TUNEL-positive neurons’ counts were significantly increased(P<0.05). The brain EB contents and BWC were dramatically decreasedcompared to SAH group (P<0.05).Conclusions1. PPARβ may be involved in the pathological process of EBI afterSAH, through NF-κB at transcriptional level, which is mediating the expression of MMP-9that lead to anoikis in neurons of hippocampus.2. GW0742injected at72h after SAH can increase expression ofPPARβ. It may have a potential protection of brain after SAH by reducinganoikis, BBB permeability and BWC.