The brain protects itself from blood-borne pathogens and toxins by severely restricting the transport of cells, particles and most hydrophilic molecules across the vascular endothelium of blood vessels in the brain. This protective mechanism is known as the blood-brain barrier, or BBB.Even hydrophobic molecules which can cross the endothelial cell membranes are frequently pumped back into the bloodstream by astrocytes closely associated with the endothelium. Blood-borne molecules which the brain requires for metabolic functions (glucose, amino acids) or systemic signal/response mechanisms (insulin, neurotransmitters) each have specific tranporters for brain uptake. These transport mechanisms are often utilized for pharmacological intervention by identifying active analogs (L-DOPA) of the naturally transported molecules that can take advantage of the transporters. Some systemic vasodilators (bradykinin) or administering i.v. mannitol to increase the osmotic strength of the blood can briefly increase the BBB permeability.