Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2023
Proprotein convertase subtilisin/kexin type 9 inhibitor ameliorates cerebral ischemia in mice by inhibiting inflammation.
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Chen Linyu, Du Yuanyuan, Qiao Huimin, Yang Lan, Zhang Peipei, Wang Jing, Zhang Cong, Jiang Wei, Xu Renhao, Zhang Xiangjian
Аннотация
OBJECTIVES: To investigate the potential protective effects of evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on ischemic stroke and its underlying mechanisms.
MATERIALS AND METHODS: We established a mouse model with distal middle cerebral artery occlusion. We evaluated the therapeutic effects through neurological function and infarct size, while the underlying mechanisms were elucidated using western blotting and real-time polymerase chain reaction.
RESULTS: Evolocumab improved neurological recovery, reduced the infarct volume, suppressed the activation of Toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB), and attenuated the increased levels of IL-1β and TNF-α after cerebral ischemia.
CONCLUSION: Evolocumab protects against cerebral ischemic injury by inhibiting inflammation. Therefore, the TLR4/NF-кB pathway may represent a major mechanism in ischemic stroke.
MATERIALS AND METHODS: We established a mouse model with distal middle cerebral artery occlusion. We evaluated the therapeutic effects through neurological function and infarct size, while the underlying mechanisms were elucidated using western blotting and real-time polymerase chain reaction.
RESULTS: Evolocumab improved neurological recovery, reduced the infarct volume, suppressed the activation of Toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB), and attenuated the increased levels of IL-1β and TNF-α after cerebral ischemia.
CONCLUSION: Evolocumab protects against cerebral ischemic injury by inhibiting inflammation. Therefore, the TLR4/NF-кB pathway may represent a major mechanism in ischemic stroke.