C-reactive Protein Involved In Cerebral Ischemia/reperfusion Injury: Possible Pro-inflammatory Mechanism

Objectives: The aim of this study was to investigate the involvement of C-reactive protein (CRP) in cerebral ischemia/reperfusion injury and its possible pro-inflammatory effects. Methods: CRP levels in the ischemic brain tissue or in the circulation were analyzed in an in vivo rat brain ischemia model of middle cerebral artery occlusion and in the vascular cells under inflammatory or hypoxia conditions. To determine the possible effects of CRP on brain microvessel endothelium, we examined the effects of CRP on brain microvascular endothelial cells (BMECs) with emphasis on its relation to cell adhesions molecules. We also evaluated simvastatin or pioglitazone treatment whether has protective effects. Results: In the present work, a significant increase of CRP in the serum and the cortex but not the hippocampus was observed in the rats exposed to cerebral ischemia and reperfusion. In brain endothelial cells and monocytes, CRP was significantly induced by hypoxia or lipopolysaccharide treatment. Incubation of BMECs with CRP significantly increased lactate dehydrogenase leakage, elicited significant expression of adhesion molecules and stimulated rapidly phosphorylation of signal transducer and activator of transcription-3 on tyrosine residues. Pretreatment with simvastatin, pioglitazone and AG490 significantly reduced these inductions of adhesion molecules. Conclusion: These findings indicate that CRP elevated in the ischemic brain or in the brain endothelial cells could result in much higher levels in microdomain in the brain infarction area, and CRP might be involved directly in the inflammatory processes in the cerebrovascular wall by up-regulations of cell adhesion molecules and thus will contribute to the brain injury.