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

ABSTRACT

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 h. After 24 h 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 160 mg/kg ART intraperitoneally (i.p.) 10 min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. An 80 mg/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-κB (NF-κB), tumor necrosis factor (TNF)-α, 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-κB pathway.