ArticlePloS one2014
Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- or NMDA-dependent mechanism?
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- TheBrain plasticity (Amsterdam, Netherlands) · 2022Pooled it
- Article
- Serum PAI-1/BDNF Ratio Is Increased in Alzheimer's Disease and Correlates with Disease Severity.ACS omega · 2023Article
- Alzheimer's Disease Severity Is Associated with an Imbalance in Serum Levels of Enzymes Regulating Plasmin Synthesis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.Journal of thrombosis and thrombolysis · 2021Article
- Retraction: Exogenous t-PA Administration Increases Hippocampal Mature BDNF Levels. Plasmin- or NMDA-Dependent Mechanism?PloS one · 2021Article
- Spinosin Attenuates Alzheimer's Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity.Biomolecules & therapeutics · 2020Article
- Combined Treatment With 2-(2-Benzofu-Ranyl)-2-Imidazoline and Recombinant Tissue Plasminogen Activator Protects Blood-Brain Barrier Integrity in a Rat Model of Embolic Middle Cerebral Artery Occlusion.Frontiers in pharmacology · 2020Article
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
- Amyloid beta soluble forms and plasminogen activation system in Alzheimer's disease: Consequences on extracellular maturation of brain-derived neurotrophic factor and therapeutic implications.CNS neuroscience & therapeutics · 2019Review
- Role of t-PA and PAI-1 variants in temporal lobe epilepsy in Chinese Han population.BMC neurology · 2019Article
- Post-synaptic Release of the Neuronal Tissue-Type Plasminogen Activator (tPA).Frontiers in cellular neuroscience · 2019Article
- Depression and chronic heart failure in the elderly: an intriguing relationship.Journal of geriatric cardiology : JGC · 2018Review
- Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons.Molecular neurobiology · 2016Article
- Androgen Modulation of Hippocampal Structure and Function.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2016Review
- The Role of TLR4 and Fyn Interaction on Lipopolysaccharide-Stimulated PAI-1 Expression in Astrocytes.Molecular neurobiology · 2015Article
- Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.PloS one · 2015Article
- Article
Corrections and comments
- Retraction · 2021-08-03Concerns/Issues about Data · Duplication of/in Image · Investigation by Third Party · Original Data and/or Images not Provided and/or not Available · · see also: https://pubpeer.com/publications/70F62C4742D329112CF5DC5DA7FDC7
- Retracted
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling.
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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.