Electrical resistance across the blood‐brain barrier in anaesthetized rats: a developmental study.

1. Ion permeability of the blood‐brain barrier was studied by in situ measurement of transendothelial electrical resistance in anaesthetized rats aged between 17 days gestation and 33 days after birth, and by electron microscopic examination of lanthanum permeability in fetal and neonatal rats aged up to 10 days old. 2. The blood‐brain barrier in 17‐ to 20‐day fetuses had a resistance of 310 omega cm2 but was impermeable to lanthanum, and therefore had properties intermediate between leaky and tight epithelia. 3. From 21 days gestation, the resistance was 1128 omega cm2, indicating a tight blood‐brain barrier and low ion permeability. There was little further change in barrier resistance after birth, and in 28‐ to 33‐day rats, when the brain barrier systems are mature in other ways, vessels had a mean resistance of 1462 omega cm2. 4. In the tight blood‐brain barrier, arterial vessels had a significantly higher resistance than venous vessels, 1490 and 918 omega cm2 respectively. In vessels less than 50 microns diameter and within the normal 60 min experimental period, there was no significant variation in vessel resistance. 5. Hyperosmotic shock caused a rapid decay in resistance (maximal within 5 min), and after disruption of the blood‐brain barrier, vessel resistance was 100‐300 omega cm2 in both arterial and venous vessels, and the effect was reversible. After the application of metabolic poisons (NaCN plus iodoacetate) and low temperature there was a similarly low electrical resistance. 6. It is concluded that the increase in electrical resistance at birth indicates a decrease in paracellular ion permeability at the blood‐brain barrier and is required for effective brain interstitial fluid ion regulation.

[1]  R. Keep,et al.  The control of potassium concentration in the cerebrospinal fluid and brain interstitial fluid of developing rats. , 1987, The Journal of physiology.

[2]  C. Johanson Ontogeny and Phylogeny of the Blood-Brain Barrier , 1989 .

[3]  T. Reese,et al.  Junctions in the meninges and marginal glia , 1975, The Journal of comparative neurology.

[4]  I Hüttner,et al.  Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. , 1984, Laboratory investigation; a journal of technical methods and pathology.

[5]  E. Windhager,et al.  NATURE OF SHUNT PATH AND ACTIVE SODIUM TRANSPORT PATH THROUGH FROG SKIN EPITHELIUM. , 1964, Acta physiologica Scandinavica.

[6]  S. Rapoport,et al.  Osmotic opening of tight junctions in cerebral endothelium , 1973, The Journal of comparative neurology.

[7]  S. Rapoport,et al.  Regulation of the microenvironment of peripheral nerve: Role of the blood-nerve barrier , 1987, Progress in Neurobiology.

[8]  C. Crone Lack of selectivity to small ions in paracellular pathways in cerebral and muscle capillaries of the frog. , 1984, The Journal of physiology.

[9]  D. Maxwell,et al.  Development of the blood vessels and extracellular spaces during postnatal maturation of rat cerebral cortex , 1970, The Journal of comparative neurology.

[10]  W. Oldendorf,et al.  The large apparent work capability of the blood‐brain barrier: A study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat , 1977, Annals of neurology.

[11]  S. Rapoport,et al.  Cerebrovascular Permeability Coefficients to Sodium, Potassium, and Chloride , 1986, Journal of neurochemistry.

[12]  S. Olesen,et al.  Electrical resistance of brain microvascular endothelium , 1982, Brain Research.

[13]  T. Reese,et al.  JUNCTIONS BETWEEN INTIMATELY APPOSED CELL MEMBRANES IN THE VERTEBRATE BRAIN , 1969, The Journal of cell biology.

[14]  N. Saunders,et al.  THE DEVELOPMENT OF THE HUMAN BLOOD‐BRAIN AND BLOOD‐CSF BARRIERS , 1986, Neuropathology and applied neurobiology.

[15]  S. Rapoport,et al.  Testing of a hypothesis for osmotic opening of the blood-brain barrier. , 1972, The American journal of physiology.

[16]  M. Bundgaard Ultrastructure of frog cerebral and pial microvessels and their impermeability to lanthanum ions , 1982, Brain Research.

[17]  D. Heistad,et al.  Permeability of blood-brain barrier to various sized molecules. , 1985, The American journal of physiology.

[18]  C. Patlak,et al.  Volume regulatory influx of electrolytes from plasma to brain during acute hyperosmolality. , 1987, The American journal of physiology.

[19]  A. Hodgkin,et al.  THE IONIC BASIS OF ELECTRICAL ACTIVITY IN NERVE AND MUSCLE , 1951 .

[20]  S. Olesen,et al.  Leakiness of rat brain microvessels to fluorescent probes following craniotomy. , 1987, Acta physiologica Scandinavica.

[21]  G. Goldstein,et al.  Developmental changes in metabolism and transport properties of capillaries isolated from rat brain. , 1981, The Journal of physiology.

[22]  T. Bouldin,et al.  Differential permeability of cerebral capillary and choroid plexus to lanthanum ion , 1975, Brain Research.

[23]  C. Crone,et al.  Electrical resistance of a capillary endothelium , 1981, The Journal of general physiology.

[24]  R. Keep,et al.  Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat. , 1988, The Journal of physiology.

[25]  S. Olesen,et al.  An electrophysiological study of microvascular permeability and its modulation by chemical mediators. , 1989, Acta physiologica Scandinavica. Supplementum.

[26]  S. Rapoport,et al.  Size selectivity of blood-brain barrier permeability at various times after osmotic opening. , 1987, The American journal of physiology.

[27]  E Frömter,et al.  Route of passive ion permeation in epithelia. , 1972, Nature: New biology.

[28]  S. Olesen,et al.  Electrical resistance of muscle capillary endothelium. , 1983, Biophysical journal.

[29]  S. Olesen Rapid increase in blood-brain barrier permeability during severe hypoxia and metabolic inhibition , 1986, Brain Research.

[30]  A. Butt,et al.  High potassium selective permeability and extracellular ion regulation in the glial perineurium (blood-brain barrier) of the crayfish , 1990, Neuroscience.