Brain-Derived Neurotrophic Factor Induces Platelet Aggregation
Notice bibliographique
Résumé
Abstract Background: A large extra-cerebral pool of Brain-Derived Neurotrophic Factor (BDNF) is found in platelets. With concentrations reaching 100-1000 fold those of neurons, platelet-stored BDNF is hypothesized to play an important role in the vasculature. Aims: To investigate the effect of BDNF on platelets, alone and synergistically with traditional agonists. Methods: The presence of BDNF in platelets was confirmed by Western Blotting and confocal microscopy. The ability of platelets to release BDNF upon stimulation was assessed by ELISA on platelet releasates following stimulation by maximal concentrations of arachidonic acid, adenosine diphosphate (ADP), epinephrine, collagen, or thrombin-receptor activating peptide (TRAP). To investigate the effect of BDNF on platelet function, we used a recombinant BDNF protein (rBDNF, Peprotech) added exogenously to a preparation of washed platelets obtained from healthy volunteers. Aggregation was recorded by light transmission aggregometry over 20 minutes. Synergistic assays were used with priming (sub-threshold) concentrations of either collagen or TRAP. The dependence on secondary mediators was assessed by blocking either COX-1-dependent thromboxane formation with aspirin or the ADP-P2Y12 receptor with AR-C66096. Platelet aggregation was blocked with a GPIIbIIIa inhibitor (abciximab) to assess the contribution of outside-in signalling. Results: Western blotting showed a 14kD band for the washed platelet protein preparations and for rBDNF used as a positive control. BDNF appeared stored in granules on confocal microscopy, consistent with previous reports. BDNF in the platelet releasate was increased 5-fold following platelet aggregation induced by traditional agonists, as compared with baseline. Exogenous rBDNF had no effect on platelet aggregation at low doses (1 and 3 µg/ml), but induced complete biphasic platelet aggregation at a high dose (10 µg/ml). The secondary wave of platelet aggregation was abrogated in the presence of aspirin and AR-C66096, but they had no effect on the primary wave. Platelet aggregation was completely abolished in the presence of the GPIIbIIIa inhibitor abciximab. Synergistic studies were conducted with priming concentrations of rBDNF, collagen and TRAP which were insufficient to elicit platelet aggregation on their own. Incubation of platelets with rBDNF (3 µg/ml) potentiated the platelet responses to priming concentrations of both collagen and TRAP. Indeed, in the absence of BDNF, no platelet aggregation was seen at the concentrations used, whereas incubation with BDNF led to complete and irreversible platelet aggregation to priming concentrations of collagen and TRAP. Conclusion: Platelets contain BDNF within their granules, which they release upon platelet activation with traditional agonists. Stimulation of washed platelets with high concentrations of rBDNF induced platelets to aggregate; in the presence of low concentrations of rBDNF, platelet aggregation was potentiated in response to priming concentrations of traditional agonists. Platelet responses to rBDNF were partly dependent on secondary mediators, as inhibition of COX-1 and the ADP-P2Y12 receptor inhibited the secondary wave of aggregation. However, the primary wave of aggregation was unaltered, thereby suggesting that platelets either possess a BDNF receptor or a traditional receptor that can signal in the presence of BDNF. Further studies are needed to uncover which receptor is implicated in platelet responses to BDNF, and the physiological role of BDNF-induced platelet responses. Disclosures No relevant conflicts of interest to declare.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».