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The effects of electrical stimulation on neurons and glia of the central nervous system

J Neural Eng · 2025 · Mixed · Low evidence

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MixedLow evidencePaper 2470

Review of 124 manuscripts reports that DC stimulation can promote axonal extension toward the cathode and axon retraction at the anode, while AC stimulation can enable axonal extension in both directions with effects dependent on intensity and duration. Acros…

Study snapshot

PublicationJ Neural Eng · 2025
Study typereview
Reported directionMixed
Evidence ratingLow

Abstract

Category: Neuroscience Tags: electrical stimulation, central nervous system, neurons, glia, neurotherapeutics, rehabilitation, inflammation DOI: 10.1088/1741-2552/ae2f9c URL: pubmed.ncbi.nlm.nih.gov Overview This review paper investigates how both direct current (DC) and alternating current (AC) electrical stimulation (ES) affect cells of the central nervous system (CNS), examining their potential and current use as neurotherapeutic strategies. The discussion also explores the promise of combining ES with other treatments, and its growing role in modern clinical rehabilitation. Approach - Comprehensive review bridging basic research and clinical translation. - 124 manuscripts identified via Google Scholar provided insights into ES effects on neurons and glia in various in vitro and in vivo models. Findings - DC Stimulation: Promotes axonal extension towards the cathode and causes axon retraction at the anode, which can limit regeneration. - AC Stimulation: Alternates electrode polarity, enabling axonal extension in both directions, with effects dependent on intensity and duration of stimulation. - Glial Response: ES—AC or DC—downregulates pro-inflammatory cytokine production and upregulates anti-inflammatory cytokines, favoring A2/M2 reactive states which are conducive to regeneration. - Oligodendrocytes: DC and AC stimulation enhance oligodendrocyte precursor cell (OPC) differentiation, increasing myelin content and supporting axonal myelination. - Combinatorial Approaches: ES combined with stem cell therapy, drug delivery, or electroactive biomaterials increases the efficacy of these interventions. - Clinical Applications: Short sessions of ES can provide long-term improvements. Early clinical efforts target gait restoration, tremor reduction, and speech improvement in conditions like spinal cord injury, Parkinson’s Disease, and stroke. Conclusion ES is an evolving neurotherapeutic strategy showing promise for CNS-related diseases and injuries. In-depth understanding of ES effects on neurons and glia is vital for optimization of future clinical applications. Researchers, clinicians, and patients should be aware that electrical stimulation actively modifies central nervous system cellular environments, which directly links to health risks and benefits depending on stimulation parameters and patient context. All EMF exposure can modulate biological responses, underscoring the ongoing need for rigorous EMF safety evaluation.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typereview
Effect directionmixed
PopulationNot supplied
Sample size124
ExposureNot supplied
Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Review of 124 manuscripts reports that DC stimulation can promote axonal extension toward the cathode and axon retraction at the anode, while AC stimulation can enable axonal extension in both directions with effects dependent on intensity and duration. Across AC or DC, electrical stimulation is described as downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines, favoring A2/M2 reactive states, and enhancing OPC differentiation with increased myelin content; combinatorial approaches and short clinical sessions are reported to improve outcomes in early clinical applications.

Outcomes measured

  • axonal extension/regeneration
  • axon retraction
  • pro-inflammatory cytokine production
  • anti-inflammatory cytokine production
  • glial reactive states (A2/M2)
  • oligodendrocyte precursor cell (OPC) differentiation
  • myelin content/axonal myelination
  • clinical rehabilitation outcomes (gait restoration, tremor reduction, speech improvement)

Limitations

  • Review paper; no primary data reported in abstract
  • Search described as using Google Scholar; inclusion/exclusion criteria and quality assessment not detailed in abstract
  • Findings summarized across various in vitro and in vivo models; heterogeneity likely but not characterized in abstract
  • Stimulation parameters (e.g., intensity, duration) noted as important but not quantified in abstract
View raw extracted JSON
{
  "study_type": "review",
  "exposure": {
    "band": null,
    "source": "electrical stimulation (direct current and alternating current)",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": null,
  "sample_size": 124,
  "outcomes": [
    "axonal extension/regeneration",
    "axon retraction",
    "pro-inflammatory cytokine production",
    "anti-inflammatory cytokine production",
    "glial reactive states (A2/M2)",
    "oligodendrocyte precursor cell (OPC) differentiation",
    "myelin content/axonal myelination",
    "clinical rehabilitation outcomes (gait restoration, tremor reduction, speech improvement)"
  ],
  "main_findings": "Review of 124 manuscripts reports that DC stimulation can promote axonal extension toward the cathode and axon retraction at the anode, while AC stimulation can enable axonal extension in both directions with effects dependent on intensity and duration. Across AC or DC, electrical stimulation is described as downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines, favoring A2/M2 reactive states, and enhancing OPC differentiation with increased myelin content; combinatorial approaches and short clinical sessions are reported to improve outcomes in early clinical applications.",
  "effect_direction": "mixed",
  "limitations": [
    "Review paper; no primary data reported in abstract",
    "Search described as using Google Scholar; inclusion/exclusion criteria and quality assessment not detailed in abstract",
    "Findings summarized across various in vitro and in vivo models; heterogeneity likely but not characterized in abstract",
    "Stimulation parameters (e.g., intensity, duration) noted as important but not quantified in abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "electrical stimulation",
    "direct current",
    "alternating current",
    "central nervous system",
    "neurons",
    "glia",
    "inflammation",
    "oligodendrocytes",
    "myelination",
    "rehabilitation",
    "neurotherapeutics"
  ],
  "suggested_hubs": []
}
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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1088/1741-2552/ae2f9c
PubMed: 41418406

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