ArticleExperimental neurology2020
The p53 inactivators pifithrin-μ and pifithrin-α mitigate TBI-induced neuronal damage through regulation of oxidative stress, neuroinflammation, autophagy and mitophagy.
Article in Experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Selective CaStem cell reports · 2026Article
- Overcoming cancer drug resistance through small-molecule targeting of HSP90 and HSP70.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Fool's gold standard? Immunoperoxidase staining with the mouse monoclonal antibody (Clone 22C11) for detecting axonal pathology after traumatic brain injury.Frontiers in neuroscience · 2025Article
- Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- A Systematic Review of Traumatic Brain Injury in Modern Rodent Models: Current Status and Future Prospects.Biology · 2024Review
- Protective role of methane in traumatic nervous system diseases.Medical gas research · 2024Article
- Pifithrin-µ Induces Stress Granule Formation, Regulates Cell Survival, and Rewires Cellular Signaling.Cells · 2024Article
- Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse.Frontiers in neuroscience · 2024Article
- Detection and verification of neurodegeneration after traumatic brain injury in the mouse: Immunohistochemical staining for amyloid precursor protein.Brain pathology (Zurich, Switzerland) · 2023Article
- DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.Cellular and molecular neurobiology · 2023Article
- Neuroprotection of NRF2 against Ferroptosis after Traumatic Brain Injury in Mice.Antioxidants (Basel, Switzerland) · 2023Article
- Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials.Oxidative medicine and cellular longevity · 2023Review
- Article
- Role of autophagy and transcriptome regulation in acute brain injury.Experimental neurology · 2022Review
- Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice.Frontiers in molecular neuroscience · 2022Article
- Neurobiological Links between Stress, Brain Injury, and Disease.Oxidative medicine and cellular longevity · 2022Review
- Research Progress on the Inflammatory Effects of Long Non-coding RNA in Traumatic Brain Injury.Frontiers in molecular neuroscience · 2022Review
- Mitophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention.Oxidative medicine and cellular longevity · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. We investigated whether inhibition of p53 using pifithrin (PFT)-α or PFT-μ provides neuroprotective effects via p53 transcriptional dependent or -independent mechanisms, respectively. Sprague Dawley rats were subjected to controlled cortical impact TBI followed by the administration of PFTα or PFT-μ (2 mg/kg, i.v.) at 5 h after TBI. Brain contusion volume, as well as sensory and motor functions were evaluated at 24 h after TBI. TBI-induced impairments were mitigated by both PFT-α and PFT-μ. Fluoro-Jade C staining was used to label degenerating neurons within the TBI-induced cortical contusion region that, together with Annexin V positive neurons, were reduced by PFT-μ. Double immunofluorescence staining similarly demonstrated that PFT-μ significantly increased HO-1 positive neurons and mRNA expression in the cortical contusion region as well as decreased numbers of 4-hydroxynonenal (4HNE)-positive cells. Levels of mRNA encoding for p53, autophagy, mitophagy, anti-oxidant, anti-inflammatory related genes and proteins were measured by RT-qPCR and immunohistochemical staining, respectively. PFT-α, but not PFT-μ, significantly lowered p53 mRNA expression. Both PFT-α and PFT-μ lowered TBI-induced pro-inflammatory cytokines (IL-1β and IL-6) mRNA levels as well as TBI-induced autophagic marker localization (LC3 and p62). Finally, treatment with PFT-μ mitigated TBI-induced declines in mRNA levels of PINK-1 and SOD2. Our data suggest that both PFT-μ and PFT-α provide neuroprotective actions through regulation of oxidative stress, neuroinflammation, autophagy, and mitophagy mechanisms, and that PFT-μ, in particular, holds promise as a TBI treatment strategy.
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.