ArticlePloS one2014
Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- Integrated WGCNA and Network Pharmacology Explore the Potential Mechanisms of D-Limonene in Alleviating Traumatic Brain Injury.International journal of molecular sciences · 2026Article
- Exercise mimetics: molecular mechanisms, biological and therapeutic effects.Molecular biomedicine · 2026Review
- Hyperoside prevents osteoporosis by activating the PI3K/AKT signaling pathway to inhibit oxidative stress and promote osteogenesis.Molecular medicine reports · 2026Article
- Synaptamide regulates astroglial functional activity after cerebral cortex injury.Inflammopharmacology · 2025Article
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- BDNF-TrkB Signaling in Mitochondria: Implications for Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- A Small-Molecule TrkB/TrkC Ligand Promotes Neurogenesis and Behavioral Recovery Following Traumatic Brain Injury.Neurotrauma reports · 2025Article
- Long-term functional rescue of trauma-induced vision loss by a novel, small molecule TrkB modulator.PloS one · 2025Article
- Transient receptor potential vanilloid 1 inhibition reduces brain damage by suppressing neuronal apoptosis after intracerebral hemorrhage.Brain pathology (Zurich, Switzerland) · 2024Article
- 7, 8-dihydroxyflavone Ameliorates Cholinergic Dysfunction, Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Vascular Dementia.Neurochemical research · 2024Article
- Brain-Derived Neurotrophic Factor in Pediatric Acquired Brain Injury and Recovery.Biomolecules · 2024Review
- Neurotrophins and neural stem cells in posttraumatic brain injury repair.Animal models and experimental medicine · 2024Review
- Potential Neuroprotective Role of Neurotrophin in Traumatic Brain Injury.CNS & neurological disorders drug targets · 2024Review
- The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Activation of TrkB signaling mitigates cerebellar anomalies caused by Rbm4-Bdnf deficiency.Communications biology · 2023Article
- Involvement of Microbiome Gut-Brain Axis in Neuroprotective Effect of Quercetin in Mouse Model of Repeated Mild Traumatic Brain Injury.Neuromolecular medicine · 2023Article
- 7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells.Discover oncology · 2023Article
- Oral Administration of TrkB Agonist, 7, 8-Dihydroxyflavone Regenerates Hair Cells and Restores Function after Gentamicin-Induced Vestibular Injury in Guinea Pig.Pharmaceutics · 2023Article
- Failure to Thrive: Impaired BDNF Transport along the Cortical-Striatal Axis in Mouse Q140 Neurons of Huntington's Disease.Biology · 2023Article
- Effects of early maternal separation on the expression levels of hippocampal and prefrontal cortex genes and pathways in lactating piglets.Frontiers in molecular neuroscience · 2023Article
10 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
Tropomyosin-related kinase B (TrkB) signaling is critical for promoting neuronal survival following brain damage. The present study investigated the effects and underlying mechanisms of TrkB activation by the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) on traumatic brain injury (TBI). Mice subjected to controlled cortical impact received intraperitoneal 7,8-DHF or vehicle injection 10 min post-injury and subsequently daily for 3 days. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed. The protective effect of 7,8-DHF was also investigated in primary neurons subjected to stretch injury. Treatment with 20 mg/kg 7,8-DHF attenuated functional deficits and brain damage up to post-injury day 28. 7,8-DHF also reduced brain edema, neuronal death, and apoptosis at day 4. These changes were accompanied by a significant decrease in cleaved caspase-3 and increase in Bcl-2/Bax ratio. 7,8-DHF enhanced phosphorylation of TrkB, Akt (Ser473/Thr308), and Bad at day 4, but had no effect on Erk 1/2 phosphorylation. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels and promoted cAMP response element-binding protein (CREB) activation. This beneficial effect was attenuated by inhibition of TrkB or PI3K/Akt. 7,8-DHF also promoted survival and reduced apoptosis in cortical neurons subjected to stretch injury. Remarkably, delayed administration of 7,8-DHF at 3 h post-injury reduced brain tissue damage. Our study demonstrates that activation of TrkB signaling by 7,8-DHF protects against TBI via the PI3K/Akt but not Erk pathway, and this protective effect may be amplified via the PI3K/Akt-CREB cascades.
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