Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a PPARγ-dependent manner.

Abstract

To date, the neuroprotective effects of statins on intracerebral hemorrhage (ICH) are not well established. This study explored the effect and potential mechanism of simvastatin treatment on ICH. In the present study, the effects of simvastatin on hematoma absorption, neurological outcome, CD36 expression and microglia polarization were examined in rat model of ICH model. In the meantime, inhibitory effect of PPARγ inhibitor GW9662 was investigated following ICH. Additionally, the effect of simvastatin on PPARγ activation was also investigated in rat ICH model and primary microglia culture. Much more, the role of PPARγ and CD36 in simvastatin-mediated erythrocyte phagocytosis was also detected by using in vivo or in vitro phagocytosis models, respectively. After ICH, simvastatin promoted hematoma absorption and improved neurological outcome after ICH while upregulating CD36 expression and facilitating M2 phenotype polarization in perihematomal microglia. In addition, simvastatin increased PPARγ activation and reinforced microglia-induced erythrocyte phagocytosis in vivo and in vitro. All above effects of simvastatin were abolished by PPARγ inhibitor GW9662. In conclusion, our data suggested that simvastatin could enhance hematoma clearance and attenuate neurological deficits possibly by activating PPARγ.

• Authors: Yuelong Wang, Qianwei Chen, Qiang Tan, Zhou Feng, Zhenlin He, Jun Tang, Hua Feng, Gang Zhu, Zhi Chen
• Journal: Neuropharmacology (Neuropharmacology) Vol. 128 Pg. 244-254 (Jan 2018) ISSN: 1873-7064 [Electronic] England
• PMID: 29054366 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• 2-chloro-5-nitrobenzanilide
• Anilides
• Anticholesteremic Agents
• Antigens, CD
• Enzyme Inhibitors
• PPAR gamma
• Simvastatin

Topics

• Anilides (pharmacology)
• Animals
• Anticholesteremic Agents (adverse effects)
• Antigens, CD (metabolism)
• Cell Count
• Cerebral Hemorrhage (complications, diagnostic imaging, drug therapy)
• Disease Models, Animal
• Electrophoretic Mobility Shift Assay
• Enzyme Inhibitors (pharmacology)
• Hematoma (diagnostic imaging, etiology)
• Male
• Microglia (drug effects, metabolism, pathology)
• Neurologic Examination
• PPAR gamma (metabolism)
• Phagocytosis (drug effects)
• Protein Transport (drug effects)
• Rats
• Rats, Sprague-Dawley
• Simvastatin (adverse effects)
• Time Factors