ArticleFrontiers in aging neuroscience2021
Conversion of Reactive Astrocytes to Induced Neurons Enhances Neuronal Repair and Functional Recovery After Ischemic Stroke.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Titer- and Intervention Timing-Dependent Functional Effects of AAV9-NeuroD1 Gene Therapy on Spinal Cord Injury.Current issues in molecular biology · 2026Article
- Conversion of human glial cells into neurons in ex vivo culture of human brain tissue: Essential roles of the transcription factors NeuroD1 and Ascl1.Neural regeneration research · 2026Article
- Ferroptosis modulation enhances astrocyte-to-neuron conversion induced by a novel chemical cocktail in the hemorrhagic brain.Signal transduction and targeted therapy · 2026Article
- Neurogenin-2 Reprograms Human Microglial Lineage Cells into Neurons In Vitro and in Chimeric Brains.bioRxiv : the preprint server for biology · 2026Article
- Article
- Neurorehabilitation for cognitive and motor recovery: mechanisms, interventions, and translational advances.Frontiers in neurology · 2026Review
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- The Mechanisms and Application Prospects of Astrocyte Reprogramming into Neurons in Central Nervous System Diseases.Current neuropharmacology · 2026Review
- Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes.Current neuropharmacology · 2026Review
- Glial Cell Reprogramming in Ischemic Stroke: A Review of Recent Advancements and Translational Challenges.Translational stroke research · 2025Review
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Transcription Factor-Based Gene Therapy Enables Functional Repair of Rat Following Chronic Ischemic Stroke.CNS neuroscience & therapeutics · 2025Article
- The role of astrocyte metabolic reprogramming in ischemic stroke (Review).International journal of molecular medicine · 2025Review
- Lactoferrin Attenuates Pro-Inflammatory Response and Promotes the Conversion into Neuronal Lineages in the Astrocytes.International journal of molecular sciences · 2025Article
- Review
- Flavonoids in Brain Ischemia-Reperfusion and their Effect on Kinases as Signaling Pathway Activity.CNS & neurological disorders drug targets · 2025Article
- From Physiology to Pathology of Astrocytes: Highlighting Their Potential as Therapeutic Targets for CNS Injury.Neuroscience bulletin · 2025Review
- Runx2 Suppresses Astrocyte Activation and Astroglial Scar Formation After Spinal Cord Injury in Mice.Molecular neurobiology · 2024Article
- Targeting the neurovascular unit: Therapeutic potential of traditional Chinese medicine for the treatment of stroke.Heliyon · 2024Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The master neuronal transcription factor NeuroD1 can directly reprogram astrocytes into induced neurons (iNeurons) after stroke. Using viral vectors to drive ectopic ND1 expression in gliotic astrocytes after brain injury presents an autologous form of cell therapy for neurodegenerative disease. Cultured astrocytes transfected with ND1 exhibited reduced proliferation and adopted neuronal morphology within 2-3 weeks later, expressed neuronal/synaptic markers, and extended processes. Whole-cell recordings detected the firing of evoked action potentials in converted iNeurons. Focal ischemic stroke was induced in adult GFAP-Cre-Rosa-YFP mice that then received ND1 lentivirus injections into the peri-infarct region 7 days after stroke. Reprogrammed cells did not express stemness genes, while 2-6 weeks later converted cells were co-labeled with YFP (constitutively activated in astrocytes), mCherry (ND1 infection marker), and NeuN (mature neuronal marker). Approximately 66% of infected cells became NeuN-positive neurons. The majority (~80%) of converted cells expressed the vascular glutamate transporter (vGLUT) of glutamatergic neurons. ND1 treatment reduced astrogliosis, and some iNeurons located/survived inside of the savaged ischemic core. Western blotting detected higher levels of BDNF, FGF, and PSD-95 in ND1-treated mice. MultiElectrode Array (MEA) recordings in brain slices revealed that the ND1-induced reprogramming restored interrupted cortical circuits and synaptic plasticity. Furthermore, ND1 treatment significantly improved locomotor, sensorimotor, and psychological functions. Thus, conversion of endogenous astrocytes to neurons represents a plausible, on-site regenerative therapy for stroke.
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