Ming-Yan Yang, Ya-Wen Yu, Da-Lei Li, Teng Liu, Zhi-Xia Wang, Bai-Fang Gong, Xin-Xin Bai, Ya-Ping He, Hai-Yue Liang, Hua-Ying Fan
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引用次数: 0
Abstract
Background
Discovering new drugs for ischemic stroke is an effective intervention that may address the significant unmet clinical need of stroke. There is increasing evidence indicating that apolipoprotein E (ApoE) can be a potential candidate for the treatment of ischemic stroke. A short ApoE peptide could maintain the anti-inflammation and neuroprotection of the intact protein. Herein, we synthetized a novel ApoE memetic peptide, referred to as CS15, and explored its efficacy and neuroprotection of its innovative formulation of gold nanoparticles (GNPs) in transient focal ischemia in rat.
Methods
We examined anti-inflammatory activities of CS15 using LPS-induced inflammatory response in BV2 cells and in mice. GNPs were prepared by citrate reduction method and surface modified with CS15 to generate CS15-coated GNPs (CS15-GNPs). The accumulation and distribution of CS15-GNPs in the brain were confirmed by detecting the gold amount and fluorescent intensity. The neuroprotection of CS15 and CS15-GNPs was evaluate using middle cerebral artery occlusion (MCAO) model.
Results
The results showed that CS15 exhibited more potent anti-inflammation than COG1410. GNPs are capable of transporting CS15 to the brain, expanding its duration of action. Intranasal administration of CS15-GNPs notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation in transient focal ischemia in rat, which had much higher efficiency than free CS15.
Conclusion
CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke.
期刊介绍:
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.