2. Academic Validation
  3. Esketamine Provides Neuroprotection After Intracerebral Hemorrhage in Mice via the NTF3/PI3K/AKT Pathway

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

  • CNS Neurosci Ther. 2024 Dec;30(12):e70145. doi: 10.1111/cns.70145.
Xiaoyu Niu 1,  Yuanyuan Zheng 2 3,  Wang Wang 4,  Liwei Zhang 4,  Shaoshuai Wang 5,  Xihua Lu 1,  Junyang Wang 6,  Gaiqing Yang 7,  Ting Zhao 8,  Qiang Li 9,  Nan Li 10,  Junmin Wang 6,  Jian Wang 6,  Changsheng Li 1 11
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Henan Provincial Key Laboratory of Radiation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3 Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 4 Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • 5 Non-Commissioned Officer School of Army Medical University, Shijiazhuang, China.
  • 6 Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • 7 Department of Neurology, Zhengzhou Central Hospital, Zhengzhou University, Zhengzhou, China.
  • 8 Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.
  • 9 Department of Neurology, Shanghai Gongli Hospital of Pudong New Area, Shanghai, China.
  • 10 Department of Neurology, The 2nd Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 11 Department of Anesthesiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
PMID: 39690816 DOI: 10.1111/cns.70145
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.

Keywords

NTF3; PI3K/AKT signaling pathway; esketamine; intracerebral hemorrhage; neuroprotection.

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