ArticlePloS one2017
Therapeutic benefits of phosphodiesterase 4B inhibition after traumatic brain injury.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Inhibition of microglia priming by NLRP3 reduces the impact of early life stress and mild TBI.Journal of neuroinflammation · 2025Article
- 3,3'-Diindolylmethane improves pathology and neurological outcome following traumatic brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Review
- 3D-QSAR Studies on High-affinity Phosphodiestera.Current medicinal chemistry · 2025Article
- Microglia-mediated neuroinflammation in traumatic brain injury: a review.Molecular biology reports · 2024Review
- Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2024Article
- Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice.Cells · 2024Article
- Development of White Cabbage, Coffee, and Red Onion Extracts as Natural Phosphodiesterase-4B (PDE4B) Inhibitors for Cognitive Dysfunction:Advances in pharmacological and pharmaceutical sciences · 2024Article
- Ginger intake suppresses neutrophil extracellular trap formation in autoimmune mice and healthy humans.JCI insight · 2023Article
- Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury.International journal of molecular sciences · 2023Review
- Selective Inhibition of PDE4B Reduces Methamphetamine Reinforcement in Two C57BL/6 Substrains.International journal of molecular sciences · 2022Article
- Lateral Fluid Percussion Injury Causes Sex-Specific Deficits in Anterograde but Not Retrograde Memory.Frontiers in behavioral neuroscience · 2022Article
- Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue.Biomedicines · 2021Review
- Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.International journal of molecular sciences · 2021Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Review
- Article
- Targeting Phosphodiesterases-Towards a Tailor-Made Approach in Multiple Sclerosis Treatment.Frontiers in immunology · 2019Review
- Genetic Association of Phosphodiesterases With Human Cognitive Performance.Frontiers in molecular neuroscience · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) initiates a deleterious inflammatory response that exacerbates pathology and worsens outcome. This inflammatory response is partially mediated by a reduction in cAMP and a concomitant upregulation of cAMP-hydrolyzing phosphodiesterases (PDEs) acutely after TBI. The PDE4B subfamily, specifically PDE4B2, has been found to regulate cAMP in inflammatory cells, such as neutrophils, macrophages and microglia. To determine if PDE4B regulates inflammation and subsequent pathology after TBI, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury (2 ± 0.2 atm) and were then treated with a PDE4B - selective inhibitor, A33, or vehicle for up to 3 days post-surgery. Treatment with A33 reduced markers of microglial activation and neutrophil infiltration at 3 and 24 hrs after TBI, respectively. A33 treatment also reduced cortical contusion volume at 3 days post-injury. To determine whether this treatment paradigm attenuated TBI-induced behavioral deficits, animals were evaluated over a period of 6 weeks after surgery for forelimb placement asymmetry, contextual fear conditioning, water maze performance and spatial working memory. A33 treatment significantly improved contextual fear conditioning and water maze retention at 24 hrs post-training. However, this treatment did not rescue sensorimotor or working memory deficits. At 2 months after surgery, atrophy and neuronal loss were measured. A33 treatment significantly reduced neuronal loss in the pericontusional cortex and hippocampal CA3 region. This treatment paradigm also reduced cortical, but not hippocampal, atrophy. Overall, these results suggest that acute PDE4B inhibition may be a viable treatment to reduce inflammation, pathology and memory deficits after TBI.
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Registered trials
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