Biomaterial Database

Effect of hyperosmotic blood-brain barrier disruption on transcapillary transport in canine brain tumors. 1990

D R Groothuis, and P C Warkne, and P Molnar, and G D Lapin, and M A Mikhael

Department of Neurology, Northwestern University Medical School, Evanston Hospital, Illinois.

Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t], and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t]. The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.

UI	MeSH Term	Description	Entries
D007482	Iothalamate Meglumine	A radiopaque medium used for urography, angiography, venography, and myelography. It is highly viscous and binds to plasma proteins.	Iotalamate Meglumine,Iothalamic Acid Methylglucamine,Meglumine Iothalamate,Conray 60,Iothalamic Acid Meglumine,Meglumine Iotalamate,Methylglucamine Iotalamate,Methylglucamine Iothalamate,Iotalamate, Meglumine,Iotalamate, Methylglucamine,Iothalamate, Meglumine,Iothalamate, Methylglucamine,Meglumine, Iotalamate,Meglumine, Iothalamate,Meglumine, Iothalamic Acid,Methylglucamine, Iothalamic Acid
D008353	Mannitol	A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity.	(L)-Mannitol,Osmitrol,Osmofundin
D008955	Models, Cardiovascular	Theoretical representations that simulate the behavior or activity of the cardiovascular system, processes, or phenomena; includes the use of mathematical equations, computers and other electronic equipment.	Cardiovascular Model,Cardiovascular Models,Model, Cardiovascular
D009994	Osmolar Concentration	The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent.	Ionic Strength,Osmolality,Osmolarity,Concentration, Osmolar,Concentrations, Osmolar,Ionic Strengths,Osmolalities,Osmolar Concentrations,Osmolarities,Strength, Ionic,Strengths, Ionic
D001812	Blood-Brain Barrier	Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.	Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002199	Capillary Permeability	The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.	Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia