Bringing drugs into the injured brain and keeping them there

The delivery of pharmacological compounds to the injured brain is a huge challenge, which may predispose to drug failure and resistance. Besides the limited passage of drugs across the blood-brain barrier, which is a physical obstacle for the majority of pharmacological compounds, brain capillary cells express ATP-binding cassette (ABC) transporters on their surface, which actively remove drugs from the brain against concentration gradients. Eliminating a large number of pharmacological compounds and endogenous substrates from the brain tissue, ABC transporters play a major role for the maintenance of brain homeostasis and detoxification. The present issue summarizes current knowledge on ABC transporters in the injured brain, outlining how these efflux systems are regulated under pathological conditions, how they impede the brain accumulation of drugs and how they might contribute to the pathogenesis of neurological diseases once they become dysfunctional. This issue analyzes the validity of the concept of multidrug resistance, evaluating how ABC transporters may be modified in order to enable the development of more efficacious pharmacological treatments.