Artesunate Provides Neuroprotection against Cerebral Ischemia-Reperfusion Injury via the TLR-4/NF-kappa B Pathway in Rats

摘要

Inflammation has an important role in ischemia-reperfusion (I/R) injury. Artesunate (ART) has anti-microbial and anti-inflammatory pharmacological activities, and it is used for various types of serious malaria, including cerebral malaria. ART maintains a high concentration in the brain but little is known about the neuroprotective effect of ART against brain UR injury. We studied the neuroprotection of ART against brain I/R injury and its underlying mechanism. In this study, rats were subjected to middle cerebral artery occlusion (MCAO) for 2h. After 24h of reperfusion, neurological deficits, cerebrum water content, infarct volume, hematoxylin-eosin (H&E)-staining, myeloperoxidase (MPO) activity, and proinflammatory cytokine levels were measured. Administration of 20, 40, 80, and 160mg/kg ART intraperitoneally (i.p.) 10min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. An 80mg/kg dosage was optimal. ART significantly reduced infarct volume, suppressed MPO activity and diminished the expressions of toll-like receptor (TLR)-4, MyD88, nuclear factor-kappa B (NF-kappa B), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in the area of the ischemic cortex. The neuroprotective action of ART against focal cerebral I/R injury might be due to the attenuation of inflammation through the TLR-4/NF-kappa B pathway.