ArticleProceedings of the National Academy of Sciences of the United States of America2020
P7C3-A20 treatment one year after TBI in mice repairs the blood-brain barrier, arrests chronic neurodegeneration, and restores cognition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- P7C3 Compounds as Targeted Mitochondrial Therapeutics for Brain Disorders.CNS neuroscience & therapeutics · 2026Pooled it
- The role and mechanisms of AMPK in neurovascular unit injury in Parkinson's disease.Frontiers in aging neuroscience · 2026Pooled it
- The interplay between vitamin D3 and Nrf2 signaling: mechanistic insights and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- PDE5 inhibition restores mitochondrial function and improves neurobehavioral outcomes after repeated mild blast TBI.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Restoring mitochondrial health after blast-induced traumatic brain injury: modifiable factors and therapeutic opportunities.npj metabolic health and disease · 2026Review
- P7C3-A20 prevents whole brain radiotherapy-induced chronic hippocampal redox imbalance and neuropsychiatric impairment in mice.Redox biology · 2026Article
- From Traumatic Brain Injury to Alzheimer's Disease: Multilevel Biomechanical, Neurovascular, and Molecular Mechanisms with Emerging Therapeutic Directions.International journal of molecular sciences · 2026Review
- Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.Cell reports. Medicine · 2026Article
- Revolutionizing Therapeutic Approaches Against Pathophysiology of Alzheimer's Disease: A Therapeutic Review.Current aging science · 2026Review
- Network-based prediction and real-world patient data observation identify doxycycline as a repurposable drug in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Three-Dimensional Human Neurovascular Unit Modeling Reveals Cell-Specific Mechanisms of Traumatic Brain Injury.Journal of functional biomaterials · 2025Article
- A sensory and motor neuropathy caused by a genetic variant ofScience advances · 2025Article
- Subcellular and macrostructural immediate responders to airblast traumatic brain injury.Scientific reports · 2025Article
- Inhibiting 15-PGDH blocks blood-brain barrier deterioration and protects mice from Alzheimer's disease and traumatic brain injury.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features.Current Alzheimer research · 2025Review
- Discovery of novel protective agents for infection-related delirium through bispectral electroencephalography.Translational psychiatry · 2024Article
- Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury.Cell reports. Medicine · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
Chronic neurodegeneration in survivors of traumatic brain injury (TBI) is a major cause of morbidity, with no effective therapies to mitigate this progressive and debilitating form of nerve cell death. Here, we report that pharmacologic restoration of the blood-brain barrier (BBB), 12 mo after murine TBI, is associated with arrested axonal neurodegeneration and cognitive recovery, benefits that persisted for months after treatment cessation. Recovery was achieved by 30 d of once-daily administration of P7C3-A20, a compound that stabilizes cellular energy levels. Four months after P7C3-A20, electron microscopy revealed full repair of TBI-induced breaks in cortical and hippocampal BBB endothelium. Immunohistochemical staining identified additional benefits of P7C3-A20, including restoration of normal BBB endothelium length, increased brain capillary pericyte density, increased expression of BBB tight junction proteins, reduced brain infiltration of immunoglobulin, and attenuated neuroinflammation. These changes were accompanied by cessation of TBI-induced chronic axonal degeneration. Specificity for P7C3-A20 action on the endothelium was confirmed by protection of cultured human brain microvascular endothelial cells from hydrogen peroxide-induced cell death, as well as preservation of BBB integrity in mice after exposure to toxic levels of lipopolysaccharide. P7C3-A20 also protected mice from BBB degradation after acute TBI. Collectively, our results provide insights into the pathophysiologic mechanisms behind chronic neurodegeneration after TBI, along with a putative treatment strategy. Because TBI increases the risks of other forms of neurodegeneration involving BBB deterioration (e.g., Alzheimer's disease, Parkinson's disease, vascular dementia, chronic traumatic encephalopathy), P7C3-A20 may have widespread clinical utility in the setting of neurodegenerative conditions.
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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.