Short communicationDifferential effect of clopidogrel and aspirin on the release of BDNF from platelets
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.
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