ABSTRACT
OBJECTIVES: Intracerebral hemorrhage (ICH) is a serious public health problem with high mortality and morbidity. The current study aims to investigate the effects of rosiglitazone on the microglial distribution and the expression of PPARγ and CD36 in the ICH rat model. METHODS NEW: Sprague-Dawley male rats (n=116) were randomly divided into four groups: control, ICH, rosiglitazone, and PPARγ antagonist (GW9662). Hematoxylin-eosin staining was used to observe the brain edema in the ICH rat model. The effect of rosiglitazone on the expression of OX-42, a microglial marker, was evaluated by immunohistochemistry. Immunohistochemistry, quantitative real-time PCR, and western blot were utilized to assess the role of rosiglitazone in the expression of PPARγ and CD36. RESULTS: ICH rats exhibited a remarkable brain edema at 72 h. OX-42 expression was significantly increased in brain tissues of ICH rats. Rosiglitazone remarkably promoted the OX-42 expression in ICH rats, whereas GW9662 suppressed OX-42 expression. In addition, immunohistochemistry analysis showed that rosiglitazone markedly enhanced the expression of PPARγ and CD36 in brain tissues around the hematoma in ICH rats, while GW9662 inhibited their expression in ICH rats. Moreover, rosiglitazone significantly promoted the mRNA and protein expression of PPARγ and CD36 in the brain tissues of ICH rats, while GW9662 showed the opposite trend. CONCLUSION: Rosiglitazone may improve microglial distribution via promoting the expression of PPARγ and CD36 around the hematoma in the ICH rat model, which may provide effective therapeutic targets for the treatment of ICH.
ABSTRACT
Objective: Cerebral ischemia-reperfusion (I/R) injury is a common pathological feature in ischemic stroke. Autophagy plays a key role in I/R-induced neuronal death. Neuroprotectin D1 (NPD1) is a docosahexaenoic acid derivative with neuroprotective and anti-inflammatory properties. The purpose of this study was to investigate the mediatory role of NPD1 on I/R-induced injury and to elucidate the underlying mechanisms involved in this process.Methods: An I/R injury model was established in PC12 cells induced by oxygen and glucose deprivation/reoxygenation (OGD/R). NPD1 at increasing doses (5, 10, 20, 50, 100 nM) were added to cells one hour before OGD/R. To investigate the effect of ring finger protein 146 (RFP146) deficiency in I/R injury, PC12 cells were transiently transfected with small interfering RNF146 before further experiment.Results: Compared to the controls, OGD/R-challenged cells exhibited significantly decreased cell viability, induced oxidative stress, and excessive autophagic cell death following OGD/R. Pretreatment with NPD1 protected cells against ischemic injury as evidenced by enhanced cell survival, decreased oxidative stress markers, and a lower level of autophagy compared to drug-free group. OGD/R also increased the level of RFP146 and inhibited the expression of ß-catenin in PC12 cells. NPD1 treatment promoted the production of RNF146 and ß-catenin in cells following OGD/R experiment. Moreover, RNF146 deficiency significantly inhibited ß-catenin expression and reversed the protective effects of NPD1 in OGD/R-induced cells.Conclusion: NPD1 alleviated excessive autophagy via regulating RNF146 and Wnt/ß-catenin signaling, suggesting the potential therapeutic use of NPD1 for the protection against cerebral I/R injury.
