- Author:
Hongxuan FENG
1
;
Linghao HU
2
;
Hongwen ZHU
1
;
Lingxue TAO
1
;
Lei WU
1
;
Qinyuan ZHAO
1
;
Yemi GAO
1
;
Qi GONG
1
;
Fei MAO
2
;
Xiaokang LI
2
;
Hu ZHOU
1
;
Jian LI
2
;
Haiyan ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Blood–brain barrier; Brain ischemia; Cell cycle; Inflammation; Neuroprotection
- From: Acta Pharmaceutica Sinica B 2020;10(3):434-446
- CountryChina
- Language:English
- Abstract: Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.