Neuroprotective effect of ADS032 on acute ischemic stroke in mice
HUANG Wen
LI Ming-yang
ZHANG Yong-gang
XIONG Xiao-xing
Abstract：Objective To explore the effect and mechanism of ADS032 on neurological function in mice after acute ischemic stroke. Methods One hundred male C57BL/6 mice were randomly divided into five groups:sham operation group,model group,and low-,medium-,and high-dose ADS032 groups,with 20 mice in each group. The middle cerebral artery occlusion model was established by suture method to simulate ischemic stroke. After ischemia,ADS032 (50,100,200 mg/kg) was intraperitoneally injected once a day for 3 days. The neurological function of mice was evaluated according to the Longa score,the cerebral infarction volume was evaluated by TTC staining,the content of microglia in the infarcted cerebral tissues was detected by immunofluorescence staining,the expressions of anti-inflammatory factors interleukin (IL)-4,IL-10 and pro-inflammatory factors IL-18,IL-1β in the infarcted cerebral tissues were detected by real-time fluorescent quantitative PCR,and the expressions of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome,apoptosis-associated speck-like protein (ASC),and IL-18,IL-1β were detected by Western blotting. Results Compared with the sham operation group,the model group had significant cerebral infarction (P<0.05),aggravated neurological deficit (P<0.05),a significant increase in the number of microglia in the infarcted cerebral tissues (P<0.05),significantly increased levels of NLRP3,ASC,IL-18,and IL-1β(P<0.05),and significantly decreased levels of IL-4 and IL-10 (P<0.05). Compared with the model group,ADS032 significantly reduced the cerebral infarction volume (P<0.05),significantly improved the neurological deficit (P<0.05),significantly reduced the number of microglia in the infarcted cerebral tissues (P<0.05),significantly alleviated the neuroinflammatory response,and increased the levels of anti-inflammatory factors (P<0.05),in a dose-dependent manner. Conclusion ADS032 has a significant neuroprotective effect on acute ischemic stroke in mice,and its mechanism may be related to the inhibition of inflammatory response.
Keywords：Acute ischemic strokeADS032NeuroinflammationNeuroprotective effectMice
Publication Date：2024-07-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 415-421 )