Open AccessDl-3-n-butylphthalide Reduces Neurovascular Inflammation and Ischemic Brain Injury in Mice
Author(s) -
Chun-Sheng Yang,
Ai Guo,
Yulin Li,
Kaibin Shi,
FuDong Shi,
Minshu Li
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2019.0608
Subject(s) - medicine , ischemia , inflammation , pharmacology , stroke (engine) , brain ischemia , middle cerebral artery , downregulation and upregulation , ischemic stroke , cerebral blood flow , infiltration (hvac) , blood–brain barrier , neurovascular bundle , anesthesia , immunology , pathology , central nervous system , biology , mechanical engineering , biochemistry , engineering , gene , physics , thermodynamics
Dl-3-n-butylphthalide (NBP) is a synthetic compound that has been approved for the treatment of ischemic stroke in China. The mechanisms underlying the treatment efficacy of NBP have been reported in multiple studies and remain controversial. Here, we show that NBP treatment attenuated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion or photothrombosis-induced permanent cerebral ischemia. NBP induced downregulation of intercellular adhesion molecule 1 and protease-activated receptor 1 in cerebrovascular endothelial cells after cerebral ischemia and reperfusion. This effect was associated with the reduced brain infiltration of myeloid cells and improved cerebral blood flow after reperfusion. The beneficial effects of NBP were diminished in mice subjected to the depletion of Gr1 + myeloid cells before brain ischemia. Therefore, the restriction of neurovascular inflammation is a key mode of action for NBP in ischemic stroke.