Artesunate provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury via the TLR-4/NF-κB Pathway in Rats

抄録

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 I/R 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 2 hours. After 24 hours of reperfusion, neurological deficits, cerebrum water content, infarct volume, HE-staining, MPO activity, and proinflammatory cytokine levels were measured. Administration of 20, 40, 80, and 160 mg/kg ART i.p. 10 min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. A 80 mg/kg dosage was optimal. ART significantly reduced infarct volume, suppressed MPO activity and diminished the expressions of TLR-4, MyD88, NF-κB, TNF-α, and 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-κB pathway.