ReviewCurrent neuropharmacology2020
A Mechanistic Rationale for PDE-4 Inhibitors to Treat Residual Cognitive Deficits in Acquired Brain Injury.
Review in Current neuropharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 18 citations in OpenAlex.
- The effects of the PDE4 inhibitor roflumilast on cognitive performance after a cerebrovascular accident: a double-blind randomized placebo-controlled trial with an open label extension (ROSTMEMA).Journal of psychopharmacology (Oxford, England) · 2026Trial
- The lung-brain axis in neurodegeneration: inflammatory, immune, and vascular mechanisms with therapeutic implications.Inflammopharmacology · 2026Review
- Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.Inflammopharmacology · 2025Review
- Review
- Effects of exercise-targeted hippocampal PDE-4 methylation on synaptic plasticity and spatial learning/memory impairments in D-galactose-induced aging rats.Experimental brain research · 2024Article
- Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes.Journal of Alzheimer's disease : JAD · 2023Article
- The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice.Neurochemical research · 2022Article
- Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models.Acta pharmacologica Sinica · 2021Article
- The Dual Dose-Dependent Effects of Corticosterone on Hippocampal Cell Apoptosis After Traumatic Brain Injury Depend on the Activation Ratio of Mineralocorticoid Receptors to Glucocorticoid Receptors.Frontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with acquired brain injury (ABI) suffer from cognitive deficits that interfere significantly with their daily lives. These deficits are long-lasting and no treatment options are available. A better understanding of the mechanistic basis for these cognitive deficits is needed to develop novel treatments. Intracellular cyclic adenosine monophosphate (cAMP) levels are decreased in ABI. Herein, we focus on augmentation of cAMP by PDE4 inhibitors and the potentially synergistic mechanisms in traumatic brain injury. A major acute pathophysiological event in ABI is the breakdown of the blood-brain-barrier (BBB). Intracellular cAMP pathways are involved in the subsequent emergence of edema, inflammation and hyperexcitability. We propose that PDE4 inhibitors such as roflumilast can improve cognition by modulation of the activity in the cAMPPhosphokinase A-Ras-related C3 botulinum toxin substrate (RAC1) inflammation pathway. In addition, PDE4 inhibitors can also directly enhance network plasticity and attenuate degenerative processes and cognitive dysfunction by increasing activity of the canonical cAMP/phosphokinase- A/cAMP Responsive Element Binding protein (cAMP/PKA/CREB) plasticity pathway. Doublecourtin and microtubule-associated protein 2 are generated following activation of the cAMP/PKA/CREB pathway and are decreased or even absent after injury. Both proteins are involved in neuronal plasticity and may consist of viable markers to track these processes. It is concluded that PDE4 inhibitors may consist of a novel class of drugs for the treatment of residual symptoms in ABI attenuating the pathophysiological consequences of a BBB breakdown by their anti-inflammatory actions via the cAMP/PKA/RAC1 pathway and by increasing synaptic plasticity via the cAMP/PKA/CREB pathway. Roflumilast improves cognition in young and elderly humans and would be an excellent candidate for a proof of concept study in ABI patients.
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.