Esketamine Provides Neuroprotection After Intracerebral Hemorrhage in Mice via the NTF3/PI3K/AKT Pathway

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-12-17 DOI:10.1111/cns.70145

Xiaoyu Niu, Yuanyuan Zheng, Wang Wang, Liwei Zhang, Shaoshuai Wang, Xihua Lu, Junyang Wang, Gaiqing Yang, Ting Zhao, Qiang Li, Nan Li, Junmin Wang, Jian Wang, Changsheng Li

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Abstract

Background

Esketamine (ESK), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, modulates neurotransmitter signaling in the central nervous system. However, the specific mechanisms and therapeutic potential of ESK for intracerebral hemorrhage (ICH) remain unclear. This study aimed to investigate whether ESK promotes nerve repair and improves neurological outcomes in an experimental model of ICH.

Methods

ICH was induced in mice via collagenase injection into the striatum. Body weight, neurological impairment, and behavioral changes were assessed. ESK administration significantly improved several indicators of ICH. Comprehensive RNA transcriptome sequencing and network pharmacology analyses identified neurotrophin-3 (NTF3) and the PI3K/AKT signaling pathway as targets for ESK treatment. Western blotting and immunofluorescence detected the protein expression levels and cellular localization of NTF3.

Results

After 28 days of adeno-associated virus infection in the mouse striatum, ESK treatment significantly enhanced neuroprotection, indicating the crucial role of NTF3 in ESK-mediated neuroprotection in ICH mice. Inhibition of the PI3K/AKT pathway using the PI3K-specific inhibitor LY294002 significantly attenuated the therapeutic effects of ESK, suggesting that this pathway is involved in ESK-mediated neurorepair in ICH mice.

Conclusions

ESK treatment significantly improved functional outcomes and demonstrated neuroprotective effects in animal models of ICH. NTF3/PI3K/AKT pathway activation by ESK indicates its therapeutic potential in the treatment of ICH.

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

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.