ArticleCNS drugs2014
Perispinal etanercept for post-stroke neurological and cognitive dysfunction: scientific rationale and current evidence.
Article in CNS drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Analysis of the Mediating Role of Cytokines in the Relationship Between Nonalcoholic Fatty Liver Disease and Cognitive Impairment After Ischemic Stroke.Brain and behavior · 2026Article
- Rapid Improvement in Cerebral Palsy Following Treatment With Perispinal Etanercept: A Case Report.Cureus · 2026Article
- From anti-inflammation to pro-resolution: a new paradigm for specialized pro-resolving mediators in regulating neuroinflammation and repair after cerebral ischemia-reperfusion.Frontiers in immunology · 2026Review
- Evaluating the Safety and Effectiveness of Perispinal Etanercept for Post-Stroke Recovery: A Systematic Review.Cureus · 2025Review
- Fibrinogen and Neuroinflammation in the Neurovascular Unit in Stroke.Journal of inflammation research · 2025Review
- The Potential Role of Etanercept in the Management of Post-stroke Pain: A Literature Review.Cureus · 2023Review
- Neuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side.International journal of molecular sciences · 2022Review
- Background to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine storm.Reviews in medical virology · 2021Review
- Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions.Biomedicines · 2020Review
- Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases.International journal of molecular sciences · 2020Review
- Immediate Resolution of Hemispatial Neglect and Central Post-Stroke Pain After Perispinal Etanercept: Case Report.Clinical drug investigation · 2020Article
- Inflammation within the neurovascular unit: Focus on microglia for stroke injury and recovery.Pharmacological research · 2019Review
- TBI Rehabilomics Research: Conceptualizing a humoral triad for designing effective rehabilitation interventions.Neuropharmacology · 2019Review
- Tumor Necrosis Factor Inhibition in the Acute Management of Traumatic Optic Neuropathy.Investigative ophthalmology & visual science · 2018Article
- The meteorology of cytokine storms, and the clinical usefulness of this knowledge.Seminars in immunopathology · 2017Review
- Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents.Journal of neuroinflammation · 2016Review
- Perispinal Delivery of CNS Drugs.CNS drugs · 2016Review
- Central delivery of iodine-125-labeled cetuximab, etanercept and anakinra after perispinal injection in rats: possible implications for treating Alzheimer's disease.Alzheimer's research & therapy · 2015Article
- Transiently lowering tumor necrosis factor-α synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice.Journal of neuroinflammation · 2015Article
- Alzheimer's Disease: Exploring the Role of Inflammation and Implications for Treatment.International journal of Alzheimer's disease · 2015Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is increasing recognition of the involvement of the immune signaling molecule, tumor necrosis factor (TNF), in the pathophysiology of stroke and chronic brain dysfunction. TNF plays an important role both in modulating synaptic function and in the pathogenesis of neuropathic pain. Etanercept is a recombinant therapeutic that neutralizes pathologic levels of TNF. Brain imaging has demonstrated chronic intracerebral microglial activation and neuroinflammation following stroke and other forms of acute brain injury. Activated microglia release TNF, which mediates neurotoxicity in the stroke penumbra. Recent observational studies have reported rapid and sustained improvement in chronic post-stroke neurological and cognitive dysfunction following perispinal administration of etanercept. The biological plausibility of these results is supported by independent evidence demonstrating reduction in cognitive dysfunction, neuropathic pain, and microglial activation following the use of etanercept, as well as multiple studies reporting improvement in stroke outcome and cognitive impairment following therapeutic strategies designed to inhibit TNF. The causal association between etanercept treatment and reduction in post-stroke disability satisfy all of the Bradford Hill Criteria: strength of the association; consistency; specificity; temporality; biological gradient; biological plausibility; coherence; experimental evidence; and analogy. Recognition that chronic microglial activation and pathologic TNF concentration are targets that may be therapeutically addressed for years following stroke and other forms of acute brain injury provides an exciting new direction for research and treatment.
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.