Elsevier

Journal of Neuroimmunology

Volume 238, Issues 1–2, 15 September 2011, Pages 104-106
Journal of Neuroimmunology

Short communication
Differential effect of clopidogrel and aspirin on the release of BDNF from platelets

https://doi.org/10.1016/j.jneuroim.2011.06.015Get rights and content

Abstract

Anti-platelet treatment is a key therapeutic intervention in patients with cerebrovascular diseases. However, there is no information on its impact on the release of Brain-derived neurotrophic factor (BDNF), which is stored in large amounts in human platelets and essential for neuronal protection and repair. Here, we show that a single oral dose of clopidogrel, but not aspirin, significantly reduced the release of BDNF from platelets in healthy volunteers. These data point, for the first time, to possible differential effects of anti-platelet regimens on neuronal function in patients with cerebrovascular disorders.

Introduction

Anti-platelet therapy is a key intervention in ischemic cerebrovascular diseases. Aspirin monotherapy, the combination of aspirin with extended-release dipyridamole, and clopidogrel are options for therapy after a stroke (Level of Evidence: A) (Adams et al., 2008). The neurotrophin brain-derived neurotrophic factor (BDNF), which is stored in large amounts in platelets, is an essential mediator of neuronal protection and repair after brain injury. It has been shown in several animal models of experimental focal cerebral ischemia that systemic or local application of BDNF significantly improves the recovery of neuronal function after injury (Schabitz et al., 2007, Ploughman et al., 2009, Massa et al., 2010, Jiang et al., 2011). Therefore, there is now a growing interest in therapeutic strategies that enhance BDNF concentrations in patients suffering from stroke (Nagahara and Tuszynski, 2011). However, the impact of anti-platelet agents on the BDNF release from platelets, which may affect local BDNF concentrations at the site of cerebral injury, is unknown. It was the aim of this pilot clinical trial to investigate the impact of common anti-platelet drugs on BDNF concentrations in serum and plasma and on the release of BDNF from platelets in a group of healthy volunteers.

Section snippets

Study design

Twenty-four male volunteers with no relevant medical history were included in the study (mean age: 29 years, height: 185 cm, weight: 83.5 kg, body-mass index: 24.8 kg*m−2). On day 1, a single oral dose of 500 mg of aspirin (acetylsalicylic acid) was administered (Fig. 1). On day 29 (after four weeks without any intake of anti-platelet medication), a single oral dose of 600 mg clopidogrel was administered. Blood samples were obtained directly before administration of the study drugs (on day 1 and 29)

Results

Median platelet counts did not differ between the time points (day 1: 221*109/ml, day 2: 221*109/ml, day 29: 219*109/ml, day 30: 221*109/ml). Platelet function assays showed a strong decrease of platelet activity in the arachidonic acid assay following aspirin (median value before administration: 87.0%, after administration: 12.5%, p < 0.001) and in the adenosindiphosphate assay following clopidogrel (median value before administration: 88.0%, after administration: 15.0%, p < 0.001). There was no

Discussion

Intravascular blood clots represent one of the main causes of cerebral ischemia. The key components of these clots are platelets, which are not only important for clot formation: platelets release a large number of substances that mediate local inflammation and tissue repair (Vorchheimer and Becker, 2006). BDNF is stored in platelets and released from these cells following activation (Fujimura et al., 2002). The large difference between BDNF levels in human serum and plasma is due to a release

Disclosure

The authors declare no conflict of interest.

Source of funding

University of Rostock and Deutsche Forschungsgemeinschaft (grant LO 1145/2-2).

Acknowledgement

We thank Dr. C. Zingler and Dr. C. Burstein for the measurements of TGF-ß1 and platelet function assays.

References (14)

There are more references available in the full text version of this article.

Cited by (25)

  • Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus

    2019, Canadian Journal of Diabetes
    Citation Excerpt :

    Several studies suggest that age, sex and smoking history play important roles in BDNF activity (18,19). Stoll et al investigated the impact of various antiplatelet drugs on BDNF concentrations in serum and plasma and on the release of BDNF from platelets in healthy volunteers (20). The primary aim of this study was to investigate the correlation between platelet reactivity and BDNF serum levels in patients with type 2 diabetes who are in long-term acetylsalicylic acid (ASA) therapy.

  • The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test

    2018, Clinica Chimica Acta
    Citation Excerpt :

    Third, we did not exclude patients using antiplatelet therapy from the study. Antiplatelet drugs may influence BDNF released from platelets [56]. The majority (98.8%) of enrolled subjects currently used antiplatelet therapy in the present study.

  • Brain-derived neurotrophic factor plasma levels are increased in older women after an acute episode of low back pain

    2017, Archives of Gerontology and Geriatrics
    Citation Excerpt :

    Studies using animal models showed that pure administration of indomethacin (20 mg/kg) did not affect BDNF expression in spinal dorsal horn, and incubation of indomethacin and ibuprofen (concentration of 0.3 μm) within platelets did not affect the BDNF release in these cells during peripheral inflammation (Duric & McCarson, 2006; Hochstrasser, Ehrlich, Sperner-Unterweger, & Humpel, 2013). Similarly, Stoll et al. (Stoll, Plessow, Bratke, Virchow, & Lommatzsch, 2011) showed that a single oral dose of acetylsalicylic acid (500 mg) for one day did not affect BDNF levels in plasma, serum and platelets in a sample of healthy adult men. Rather than simple use of analgesics, factors such as: usage time, dose and medication interactions are key issues to produce significant changes in BDNF levels (Duric & McCarson, 2006; Hochstrasser et al., 2013).

View all citing articles on Scopus
View full text