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Introduction: Stroke, the second leading cause of death and disability in Europe, is primarily caused by interrupted blood supply, leading to ischemia-reperfusion (IR) injury and subsequent neuronal death. Current treatment options are limited, highlighting the need for novel therapies. Neural stem cells (NSCs) have shown promise in treating various neurological disorders, including stroke. However, the underlying mechanisms of NSC-mediated recovery remain unclear.
Methods: Eighty C57Bl/6-Tyrc-Brd mice underwent ischemic stroke induction and were divided into four groups: sham, stroke-affected, stroke-affected with basal cell medium injection, and stroke-affected with NSCs transplantation. NSCs, isolated from mouse embryos, were stereotaxically transplanted into the stroke-affected brains. Magnetic resonance imaging (MRI) and neurological scoring were used to assess recovery. Immunohistochemical analysis and gene expression assays were performed to evaluate pyroptosis and necroptosis markers.
Results: NSC transplantation significantly improved neurological recovery compared to control groups. In addition, although not statistically significant, NSCs reduced stroke volume. Immunohistochemical analysis revealed upregulation of Gasdermin D (GSDMD) expression post-stroke, predominantly in microglia and astrocytes. However, NSC transplantation led to a reduction in GSDMD signal intensity in astrocytes, suggesting an effect of NSCs on GSDMD activity. Furthermore, NSCs downregulated Mixed Lineage Kinase Domain-Like Protein () expression, indicating a reduction in necroptosis. Immunohistochemistry demonstrated decreased phosphorylated MLKL (pMLKL) signal intensity in neurons while stayed the same in astrocytes following NSC transplantation, along with increased distribution in microglia.
Discussion: NSC transplantation holds therapeutic potential in stroke recovery by targeting pyroptosis and necroptosis pathways. These findings shed light on the mechanisms underlying NSC-mediated neuroprotection and support their further exploration as a promising therapy for stroke patients.
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http://dx.doi.org/10.3389/fnmol.2024.1439994 | DOI Listing |
Adv Mater
December 2024
State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, 250100, P. R. China.
Parkinson's disease (PD) is a neurodegenerative disease caused by the dysfunction and death of dopaminergic neurons. Neural-stem-cell (NSC)-based therapy is a promising approach for the treatment of PD but its therapeutic performance is limited by low efficiency of differentiation of NSCs to dopaminergic neurons. Although electrical stimulation can promote neuronal differentiation, it is not verified whether it can induce the NSCs to specifically differentiate into dopaminergic neurons.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Neural stem cells (NSCs) have increasingly been recognized as the most promising candidates for cell-based therapies for the central nervous system (CNS) injuries, primarily due to their pluripotent differentiation capabilities, as well as their remarkable secretory and homing properties. In recent years, extensive research efforts have been initiated to explore the therapeutic potential of NSC transplantation for CNS injuries, yielding significant advancements. Nevertheless, owing to the formation of adverse microenvironment at post-injury leading to suboptimal survival, differentiation, and integration within the host neural network of transplanted NSCs, NSC-based transplantation therapies often fall short of achieving optimal therapeutic outcomes.
View Article and Find Full Text PDFBiologics
December 2024
Graduate Institute of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan.
Background And Objectives: Stem cell therapy shows great promise for treating Alzheimer's disease (AD). Cholinesterase inhibitors (ChEIs) like donepezil are well-established for alleviating AD symptoms. This study aimed to determine if combining ChEI treatment with stem cell therapy could improve therapeutic outcomes.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Research Center of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, China. Electronic address:
Background: Brachial plexu root avulsion (BPRA) commonly causes extensive motoneuron death, motor axon degeneration and denervation of biceps, leading to devastating motor dysfunction in the upper limb. Edaravone (Eda) has been proven to exert anti-oxidative and neuroprotective effects on various neurological disorders. Herein, we aimed to investigate the efficacy profile and potential mechanisms of Eda on BPRA in vitro and in vivo models.
View Article and Find Full Text PDFNeural Regen Res
November 2024
Beijing Yinfeng Dingcheng Biological Engineering Technology Co., Ltd., Beijing, China.
Exogenous neural stem cell (NSC) transplantation has become one of the most promising treatment methods for chronic stroke. Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury, which limits the ability to observe long-term behavioral recovery. Here, we used a severe stroke rat model with 150 minutes of ischemia, which produced severe behavioral deficiencies that persisted at 12 weeks, to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.
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