Psychostimulants and brain edema

Psychostimulants consumption is a serious social and health problem worldwide. The increase in drug abuse has a huge socio-economic impact in society, and more precisely carries great costs in health treatments. In fact, it is well known that cocaine, 3,4-methylenedioxymethamphetamine (MDMA), amphetamine (AMPH) and methamphetamine (METH) have several neurotoxic effects, such as neurodegeneration, neuroinflammation and blood-brain barrier (BBB) disruption. Additionally, the increase of brain water content, a pathological condition also known as brain edema, has been associated with drugs use. Disturbances in the well-regulated water homeostasis may occur under several pathological conditions leading to severe alterations in brain function. Although several studies demonstrated a link between the abuse of psychostimulants and brain edema, very little is known about the underlying mechanisms that explain such brain alterations. The water transport across cell membrane is regulated by bi-directional water channels called aquaporins (AQPs). Noteworthy, the AQP4 channel has an important role in water transport across BBB, being one of the most important at the Central Nervous System (CNS). In fact, alterations in AQP4 can originate cerebral edema due to abnormal increase in water content and consequent brain swelling. Furthermore, inflammatory mediators also seem to have a role in brain edema formation since the modulation of their action has a beneficial impact in brain edema outcome. With the present review, we aim to summarize relevant information regarding the impact of psychostimulants on brain edema. Nevertheless, it is also evident that many questions remain unanswered. Thus, in order to improve the clinical outcome of human abusers, it is of crucial importance to understand what the role of AQP4 is.