<P> The measurement of brain uptake of acetamide, antipyrine, benzyl alcohol, butanol, caffeine, cytosine, phenytoin, ethanol, ethylene glycol, heroin, mannitol, methanol, phenobarbital, propylene glycol, thiourea, and urea in ether - anesthetized newborn vs. adult rabbits shows that newborn rabbit and adult rabbit brain endothelia are functionally similar with respect to lipid - mediated permeability . These data confirmed that no differences in permeability could be detected between newborn and adult BBB capillaries . No difference in brain uptake of glucose, amino acids, organic acids, purines, nucleosides, or choline was observed between adult and newborn rabbits . These experiments indicate that the newborn BBB has restrictive properties similar to that of the adult . In contrast to suggestions of an immature barrier in young animals, these studies indicate that a sophisticated, selective BBB is operative at birth . </P> <P> The blood--brain barrier acts very effectively to protect the brain from most pathogens . Thus, blood - borne infections of the brain are very rare . Infections of the brain that do occur are often very serious and difficult to treat . Antibodies are too large to cross the blood--brain barrier, and only certain antibiotics are able to pass . In some cases, a drug has to be administered directly into the cerebrospinal fluid (CSF), where it can enter the brain by crossing the blood--cerebrospinal fluid barrier . However, not all drugs that are delivered directly to the CSF can effectively penetrate the CSF barrier and enter the brain . The blood--brain barrier becomes more permeable during inflammation . This allows some antibiotics and phagocytes to move across the BBB . However, this also allows bacteria and viruses to infiltrate the BBB . Examples of pathogens that can traverse the BBB and the diseases they cause include toxoplasma gondii which causes toxoplasmosis, spirochetes like Borrelia which causes Lyme disease, Group B streptococci which causes meningitis in newborns, and Treponema pallidum which causes syphilis . Some of these harmful bacteria gain access by releasing cytotoxins like pneumolysin which have a direct toxic effect on brain microvascular endothelium and tight junctions . </P> <P> There are also some biochemical poisons that are made up of large molecules that are too big to pass through the blood--brain barrier . This was especially important in more primitive times when people often ate contaminated food . Neurotoxins such as botulinum in the food might affect peripheral nerves, but the blood--brain barrier can often prevent such toxins from reaching the central nervous system, where they could cause serious or fatal damage . </P> <P> The blood--brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain ∼ 100% of large - molecule neurotherapeutics and more than 98% of all small - molecule drugs . Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of most brain disorders . In its neuroprotective role, the blood--brain barrier functions to hinder the delivery of many potentially important diagnostic and therapeutic agents to the brain . Therapeutic molecules and antibodies that might otherwise be effective in diagnosis and therapy do not cross the BBB in adequate amounts . </P>

In order for particles to move across the blood-brain barrier they must