The blood–brain barrier is a dynamic interface separating the brain from the circulatory system. The blood–brain barrier is formed by specialized endothelial cells and regulates the transport of essential molecules from the circulation to the brain, while also protecting the brain from harmful chemicals. This barrier also limits the ability of many systemically administered chemotherapy agents to penetrate into the central nervous system. In general, small molecules and those that are lipophilic are more likely to cross the blood–brain barrier than those that are large and lipophobic. There are mechanisms such as blood–brain barrier disruption, intra-arterial chemotherapy injection, intrathecal chemotherapy administration, or intratumoral chemotherapy administration that have been utilized to overcome the blood–brain barrier.

Blood–brain barrier disruption has been utilized in several pediatric brain tumor studies. Recently, osmotic disruption using mannitol infusion followed by intra-arterial carboplatin or methotrexate was used to treat adult and pediatric embryonal and germ cell tumors [21]. This preliminary study showed promising survival outcome. Another study disrupted the blood–brain barrier using intra-arterial mannitol injection followed by intracarotid chemotherapy and was effective in treating a large number of children with a variety of brain tumors including germ cell tumors and PNETs [22]. Other methods of blood–brain barrier disruption have been attempted and some have been shown to provide effective therapy for a variety of adult tumors.