Blood-Brain Barrier and Cognitive Function

The blood-brain barrier (BBB) is the highly specialized and selective crossing area between blood and brain, essential for brain homeostasis and functioning, formed by the endothelial cells of the cerebral microvasculature in a rich and intimate cooperation with the neighboring cells and local signaling factors from both the brain and blood sides. Its distribution throughout the brain is following the brain cytoarchitectonic patterns, each capillary serving the adjacent neurons in a privileged neurovascular interplay that ultimately responds to the manifestation of brain functions, scaled from the cellular to the system level. At the edge of our understanding, cognition stands for what makes us humans and needs the cooperation of the entire body functioning to assist homeostatic favorable conditions for its manifestation. The cerebral endothelial system is operating at this interfacing point, modulating its own phenotype in accordance with various conditions to which the organism and brain are exposed, responding with changes in its permeability and signaling processes. In this chapter we will briefly describe the multicellular assembly of the neurovascular unit from which the BBB emerges, and its contribution to the brain homeostasis by dynamic neurovascular and neurometabolic coupling processes. Further, we will refer to the principal morphologic and functional features of the BBB from which its specific properties arise, making it not just a physical selective barrier, but also a metabolic, neuroimmune and endocrine interface. We will touch on the physiological implications of BBB and neurovascular coupling on high brain functions and cognition, in normal or disease-associated conditions

Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review

Anabolic androgenic steroids (AAS), simply called “androgens”, represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints. The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis. Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies. However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population. The influence of androgen excess on the platelet activity and fluid–coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential

Taurine and Its Derivatives: Analysis of the Inhibitory Effect on Platelet Function and Their Antithrombotic Potential

Taurine is a semi-essential, the most abundant free amino acid in the human body, with a six times higher concentration in platelets than any other amino acid. It is highly beneficial for the organism, has many therapeutic actions, and is currently approved for heart failure treatment in Japan. Taurine has been repeatedly reported to elicit an inhibitory action on platelet activation and aggregation, sustained by in vivo, ex vivo, and in vitro animal and human studies. Taurine showed effectiveness in several pathologies involving thrombotic diathesis, such as diabetes, traumatic brain injury, acute ischemic stroke, and others. As human prospective studies on thrombosis outcome are very difficult to carry out, there is an obvious need to validate existing findings, and bring new compelling data about the mechanisms underlying taurine and derivatives antiplatelet action and their antithrombotic potential. Chloramine derivatives of taurine proved a higher stability and pronounced selectivity for platelet receptors, raising the assumption that they could represent future potential antithrombotic agents. Considering that taurine and its analogues display permissible side effects, along with the need of finding new, alternative antithrombotic drugs with minimal side effects and long-term action, the potential clinical relevance of this fascinating nutrient and its derivatives requires further consideration