Peroxisome Proliferator-Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats

Background and Purpose Early brain injury is proposed to be the primary cause of the poor outcome after subarachnoid hemorrhage (SAH), which is closely related to the neural apoptosis. To date, the relationship between peroxisome proliferator-activated receptor / (PPAR/) and nuclear factor-B/matrix metalloproteinase-9 (NF-B/MMP-9) pathway, both of which are closely related to apoptotic effects, has been poorly studied in SAH. The present study was undertaken to evaluate the effects of PPAR/ on early brain injury and NF-B/MMP-9 pathway after SAH in rats. Methods SAH model was established by injecting nonheparinized autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Adenoviruses or small interfering RNAs were injected into the right lateral cerebral ventricle to, respectively, up- or downregulate PPAR/ expression before SAH. All animals were assessed with a neurological score and then killed at 24 hours after SAH surgery. The indexes of brain water content, blood-brain barrier permeability, and apoptosis were used to detect brain injury. The expression of PPAR/, NF-B, and MMP-9 were measured by immunohistochemistry, gelatin zymography, and Western Blot methods, respectively. In addition, GW0742, a specific agonist of PPAR/, was used to treat SAH in rats, the effects of which were evaluated by neurological scoring and Evans blue extravasation. Results Overexpression of PPAR/ by adenoviruses treatment significantly ameliorated brain injury with improvement in neurological deficits, brain edema, blood-brain barrier impairment, and neural cell apoptosis at 24 hours after SAH in rats, whereas downregulation of PPAR/ by small interfering RNAs administration resulted in the reverse effects of the above. The expression levels of NF-B and MMP-9 were markedly downregulated when PPAR/ increased after PPAR/ adenovirus transfection and upregulated when PPAR/ decreased by PPAR/ small interfering RNAs treatment. Moreover, GW0742 improved neurological deficits and reduced Evans blue extravasation at 24 hours after SAH. Conclusions PPAR/'s overexpression may attenuate early brain injury after rats' SAH administration, which reduces neural apoptosis possibly through blocking NF-B/MMP-9 pathway.