ArticleJournal of neuroinflammation2022
Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07588932 (Relying on Pharmacotherapy to Improve Motor Gains of Robot-Assisted Upper-Extremity Rehabilitation in Chronic Stroke Survivors), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Relying on Pharmacotherapy to Improve Motor Gains of Robot-Assisted Upper-Extremity Rehabilitation in Chronic Stroke Survivors
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.Frontiers in pharmacology · 2023Pooled it
- Molecular mechanisms of blood-brain barrier dysfunction caused by obesity: pathophysiological understandings and treatment targets.Metabolic brain disease · 2026Review
- Targeting microglial PANoptosis through AMPK activation: Metformin as a promising therapy for spinal cord injury.Journal of pharmaceutical analysis · 2026Article
- Metformin and Sitagliptin Impact the Brain Kynurenine Pathway: Region-Specific Modulation of Neuroactive Metabolites in Non-Diabetic Male Rats.Molecules (Basel, Switzerland) · 2026Article
- Metformin's protection against blood-brain barrier disruption and neuronal dysfunction under oxygen-glucose deprivation and tobacco smoke and e-vape chemical exposure.Fluids and barriers of the CNS · 2025Article
- Immunomodulation With Local, Sustained Delivery of Pituitary Adenylate Cyclase Activating Polypeptide Results in Improved Functional Recovery in Stroke-Injured Mice.Advanced healthcare materials · 2025Article
- Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice.BMC biology · 2025Review
- Primitive and Definitive Neural Precursor Cells Are Present in Human Cerebral Organoids.International journal of molecular sciences · 2024Article
- Article
- Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review.International journal of molecular sciences · 2024Review
- Spinal Cord Injury Management Based on Microglia-Targeting Therapies.Journal of clinical medicine · 2024Review
- Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.Translational psychiatry · 2024Article
- The Antidiabetic Drug Metformin Attenuated Depressive and Anxiety-like Behaviors and Oxidative Stress in the Brain in a Rodent Model of Inflammation Induced by Lipopolysaccharide in Male Rats.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis.Neurochemical research · 2024Article
- Integrative Analysis of Machine Learning and Molecule Docking Simulations for Ischemic Stroke Diagnosis and Therapy.Molecules (Basel, Switzerland) · 2023Article
- Metformin Improves Functional Outcomes, Activates Neural Precursor Cells, and Modulates Microglia in a Sex-Dependent Manner After Spinal Cord Injury.Stem cells translational medicine · 2023Article
- Permeability of Metformin across an In Vitro Blood-Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs).Pharmaceutics · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeonatal stroke is a devastating insult that can lead to life-long impairments. In response to hypoxic-ischaemic injury, there is loss of neurons and glia as well as a neuroinflammatory response mediated by resident immune cells, including microglia and astrocytes, which can exacerbate damage. Administration of the antidiabetic drug metformin has been shown to improve functional outcomes in preclinical models of brain injury and the cellular basis for metformin-mediated recovery is unknown. Given metformin's demonstrated anti-inflammatory properties, we investigated its role in regulating the microglia activation and used a microglia ablation strategy to investigate the microglia-mediated outcomes in a mouse model of neonatal stroke.
methodsHypoxia-ischaemia (H-I) was performed on post-natal day 8. Metformin was administered for one week, starting one day after injury. Immunohistochemistry was used to examine the spatiotemporal response of microglia and astrocytes after hypoxia-ischaemia, with or without metformin treatment. To evaluate the effects of microglia depletion after hypoxia-ischaemia, we delivered Plexxikon 5622 for 1 or 2 weeks post-injury. The regional pattern of microglia and astrocyte depletion was assessed through immunohistochemistry. Motor behaviour was assessed with the righting reflex, hindlimb suspension, grip strength and cylinder tests.
resultsHerein, we revealed a spatiotemporally regulated response of microglia and astrocytes after hypoxia-ischaemia. Metformin treatment after hypoxia-ischaemia had no effect on microglia number and proliferation, but significantly reduced microglia activation in all regions examined, concomitant with improved behavioural outcomes in injured mice. Plexxikon 5622 treatment successfully ablated microglia, resulting in a > 90% depletion in microglia in the neonatal brain. Microglia rapidly repopulated upon treatment cessation of Plexxikon. Most interesting, microglia ablation was sufficient to reduce functional deficits after hypoxia-ischaemia, mimicking the effects of 1 week of metformin treatment post-injury.
conclusionThese results highlight the importance of regulating the neuroinflammatory response after neonatal stroke to promote recovery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.