Blood Barriers Research Articles

Therapeutic apheresis therapy for ABO-incompatible renal transplantations.

The most important transplantation antigen system for organ transplantation is the ABO blood group system. Crossing the blood barrier is usually not done except in emergency cases such as liver transplantations for fulminant hepatitis. Early experiences of allograft transplantations across the blood barriers were discouraging. In the 1970s, clinical trials were started transplanting kidneys of subgroup A2 into blood group O recipients because the tissues of the A2 subgroup express a lower amount of A antigens compared with subgroup A1. The recipients required no special treatment and received the standard immunosuppressive regimen as used in blood group identical cases. Many early graft loses immediately after transplantations were experienced, but these trials resulted in an excellent graft survival rate. A few centers have adapted the concept of A2 kidneys to non-A recipient transplantations with successful results by reducing anti-A blood type titers prior to transplantations. In the early 1980s, the possibility of bridging the ABO barrier was tested by several groups. A1 and B kidneys from living donors were also successfully transplanted across the blood barrier using quadruple immunosuppressive drugs and splenectomy. Since 1989, the largest number of ABO-incompatible renal transplantations have been performed in Japan because of the limited numbers of cadaveric donors. Approximately 400 cases have been successfully transplanted across the blood barrier at many centers in Japan. Owing to novel immunosuppressive drugs, the ABO-incompatible allografts exhibited a level of function comparable with that of ABO-matched allografts even though anti-A or anti-B antibodies had returned to the circulation of the recipients. In this article, we describe the historical background, the current therapeutic strategies including apheresis therapy for the ABO-incompatible transplantations, and the experiences at our institution.

Neuropathological features of mitochondrial disorders

Genetic defects affecting the mitochondrial respiratory chain comprise an important cause of encephalomyopathies. Considering the structural complexity of the respiratory chain, its dual genetic control, and the numerous nuclear genes required for proper assembly of the enzyme complexes, the phenotypic heterogeneity is not surprising. From a neuropathological view point, application of in situ hybridization and immunohistochemistry to study the choroid plexus and brain–blood barrier in ‘prototypes’ of mitochondrial encephalopathies have revealed alterations that we think are important in the pathogenesis of central nervous system dysfunction in these disorders. As the role of the blood–cerebrospinal fluid (CSF) and brain–blood barriers in mitochondrial encephalopathies is better understood, manipulation of their functions offers promises for therapeutic interventions.

Anti-AB titer changes in patients with ABO incompatibility after living related kidney transplantations: survey of 101 cases to determine whether splenectomies are necessary for successful transplantation.

A shortage of organ donors for transplantation has become a serious problem throughout the world. To overcome this problem, transplantations across ABO blood barriers have been performed with some success. In general, however, the graft survival rate for transplantation with ABO incompatibility is lower than that of transplantation with ABO compatibility. Unfortunately, the mechanism by which isohemagglutinins might injure an ABO-incompatible graft remains uncertain. Here, the pre- and posttransplantation anti-AB titers in patients who received transplants from ABO-incompatible living donors are reviewed and the pathological findings are compared. One hundred and one patients underwent ABO-incompatible living related kidney transplantation (i-LKT) between January 1989 and October 1999 at our hospital. Plasmapheresis and immunoadsorption were performed in all of the i-LKT patients before the transplantation to remove anti-AB antibodies. A splenectomy was also performed during the operation, followed by the local irradiation of the graft with a dose of 150 rad. The anti-AB titers and pathological findings for 93 i-LKT patients, excluding 8 patients who died, were then examined. Immediately after the i-LKT, the anti-AB titer dropped rapidly to below 1:4 in all 93 cases. Seventy of patients (70/93, 75%) showed no elevation in their anti-AB titer during their follow-up. However, the remaining 23 patients (23/93, 25%) showed a significant elevation of their anti-AB titer to over 1:16. Sixteen of these patients (16/93, 17%) exhibited an anti-AB titer of over 1:32. Out of these 16 patients, 11 patients (11/16, 69%) lost their grafts. The anti-AB titer in the remaining five patients (5/16, 31%) spontaneously decreased without any special treatment. Seven patients (7/93, 8%) exhibited an elevated titer of 1:16. Out of these patients, only one patient (1/7, 14%) lost his graft. The elevated titers in the remaining six patients (6/7, 86%) eventually decreased. The graft function improved in patients whose elevated anti-AB titers eventually decreased. Control patients (ABO-compatible kidney transplant patients) showed a normal elevation of their titer values compared with preoperative titers. Pathological findings showed severe humoral rejections in all cases with high anti-AB titers that lost grafts. Humoral rejection was also detected in most of the patients whose anti-AB titer was elevated to over 1:16 after the transplantation, but excellent renal function was resumed once the titers decreased to below 1:4. In 23 out of 93 i-LKT patients (25%), the anti-AB titers were significantly elevated after the splenectomy. In view of other reports of i-LKT without splenectomy, we feel that a splenectomy in i-LKT patients might be unnecessary. Pathological evidence suggests that the decrease in the anti-AB titer after transplantation might be the net result of plasmapheresis before the operation and the adsorption of antibodies to the endothelium of the transplanted organ after the operation, neither of which is influenced by a splenectomy.

Blood barriers of the insect.

The blood-brain barrier (BBB) ensures brain function in vertebrates and insects by maintaining ionic integrity of the neuronal bathing fluid. Without this barrier, paralysis and death ensue. The structural analogs of the BBB are occlusive (pleated-sheet) septate and tight junctions between perineurial cells, glia and perineurial cells, and possibly between glia. Immature Diptera have such septate junctions (without tight junctions) while both junctional types are found in the imago. Genetic and molecular biology of these junctions are discussed, namely tight (occludin) and pleated-sheet septate (neurexin IV). A temporal succession of blood barriers form in immature Diptera. The first barrier forms in the peripheral nervous system where pleated-sheet septate junctions bond cells of the nascent (embryonic) chordotonal organs in early neurogenesis. At the end of embryonic life, the central nervous system is fully vested with a blood-brain barrier. A blood-eye barrier arises in early pupal life. Future prospects in blood-barrier research are discussed.

Alveolar vascularization of the lung in a lamb model of congenital diaphragmatic hernia.

Pulmonary hypoplasia and pulmonary hypertension are factors limiting the survival of infants with congenital diaphragmatic hernia (CDH). A reduction in the number of pre-acinar pulmonary vessels and increased muscularization are the structural lesions implicated as causes of irreversible hypoxemia. Whether there is a reduction in the number of air-blood barriers, which represent the capillary surface area of the lung involved in gas exchange, is unknown. We sought to determine if the lungs of CDH lambs have: (1) a reduction in total capillary surface area proportionate to the reduction in the total alveolar surface area of the lung; and/or (2) a disproportionate reduction in the number of capillaries (air blood barriers) within each acinus. The latter measurement was determined by calculating the capillary load which we defined as the number of air blood barriers/unit of surface density. At 80 d gestation (pseudoglandular period), a diaphragmatic hernia was created surgically in one lamb fetus of a twin gestation. At term, the fetuses were removed, the chests opened and the lungs fixed by a tracheal infusion of 1.5% glutaraldehyde at 25 cm of water pressure. Tissues from the lower lobes were examined by light and electron microscopy. Using computerized interactive morphometry, alveolar and capillary surface area, and capillary load were determined by intersection and point counting for the right and left lungs. The data show that the total alveolar surface area of the left CDH and control lungs were 1.8 +/- 0.8 m2 and 6.1 +/- 1.1 m2 (p < 0.01), respectively, and for the right CDH and control lungs 2.5 m2 +/- 0.1 and 11.2 +/- 1.9 m2 (p < 0.01), respectively. The total capillary surface area for the left CDH and control lungs were 0.7 +/- 0.3 m2 and 2.8 +/- 1.2 m2 (p < 0.05), respectively, and for the right CDH and control lungs 0.9 +/- 0.3 m2 and 3.8 +/- 1.5 m2 (p < 0.05), respectively. The capillary load was not statistically different. These findings demonstrate that the lungs in CDH are deficiently vascularized at the alveolar surface due to a reduction in the total alveolar surface area. Each acinus contains the same number of air blood barriers per unit of alveolar surface area indicating a normal acinar composition.

Arachidonate transport through the blood-retina and blood-brain barrier of the rat during aging

The permeability-surface area product ( PS) of [1- 14C]arachidonate at the blood-retina (BRB) and blood-brain barrier (BBB) was determined after short carotid perfusion in Wistar rats at 4, 12 and 28 months of age. For the visual system structures, parietal and frontal cortex, striatum, hypothalamus, hippocampus and olfactory bulb there was no significant difference among mean PSs in any age group. Our results indicate that: (1) arachidonate is able to cross at relevant rate BRB and BBB; (2) in all brain regions except retina, optic tract and hippocampus, blood barriers have a transport capacity for arachidonate significantly higher than that for docosahexaenoate and palmitate as well; (3) aging does not affect influx into retina and other structures of rat central nervous system of the arachidonate, a metabolic substrate rapidly incorporated into microcapillary and brain lipids, and for which simple diffusion transport across the BRB and BBB may be postulated.

Blood barriers of the epididymis and vas deferens act asynchronously with the blood barrier of the testis in the mink (Mustela vison).

The purpose of the present study was to determine whether the blood barrier of the epididymis and vas deferens acted synchronously or not with the blood barrier of the testis. The permeability of the blood-epididymis and blood-vas deferens barrier was tested in neonatal kit mink up to puberty and monthly in adult minks throughout the annual seasonal reproductive cycle. Attention was focused particularly on time intervals when the blood barrier of the testis has been documented to be permeable, namely, before puberty and during testicular regression in the adult. One of two electron-opaque permeability tracers was perfused into the blood stream: horseradish peroxidase (HRP) or lanthanum nitrate. The convoluted tube of the epididymis was divided into three anatomical regions: the caput, corpus, and cauda. The vas deferens was divided into proximal and distal regions. At birth and throughout puberty, the three regions of the epididymis and the two of the vas deferens showed a lumen and a competent blood barrier. In the adult, a lumen persisted in the epididymis and vas deferens throughout the annual seasonal reproductive cycle, and the blood barrier of the excurrent duct remained impermeable even when the blood barrier in the testis became momentarily permeable during testicular regression. When HRP was used to test the permeability of the blood-tissue barrier of the excurrent ducts, no tracer deposits were observed on the lumenal surface of the epithelium. Conversely, when lanthanum served as the tracer, deposits of the probe were associated with microvilli and intracellular membranes despite impermeability of tight junctions. The data show that the lanthanum technique can yield false-positive results. The findings also indicate that 1) a blood-excurrent duct barrier is established before the blood-testis barrier and 2) the two barriers act asynchronously. It is therefore plausible that they are modulated by distinct factors.

Observations on the blood and perineurial permeability barriers of surviving nerve allografts in immunodeficient and immunosuppressed rats.

The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve, the blood-nerve barrier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vessels and accumulate around the nerve. Nerves from ACI rats were transplanted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish peroxidase, which spread into endoneurial tissue. Electron microscopy revealed that horseradish peroxidase escaped from endoneurial vessels through intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the endoneurial vessels, like those in normal nerves, were impermeable to horseradish peroxidase. The perineurium-nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons were grouped into numerous minifascicles at nerve anastomosis zones at 24 weeks. Each nerve fascicle was surrounded by an impermeable perineurium. These results demonstrate that regenerated axons in long-term surviving nerve allografts and at anastomosis zones are protected by permeability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (grafts to nude rats) even when immunosuppression with cyclosporin A is required to prevent allograft rejection (grafts to Fischer rats).

System Approach to the Transepithelial Transport across Rat Jejunal Enterocytes: Effect of Cytochalasin B, Colchicine, and Ethylenediaminetetraacetic Acid on Butyric Acid Transport

A three-compartment physical model is devised for transepithelial passive transport across intestinal cells. The mathematical equations derived from the model allow the simultaneous and quantitative measurements, in the form of permeability coefficients, of solute transport across both the luminal–serosal and serosal–blood barriers. The proposed model is used to study the involvement of the cytoskeleton in butyric acid absorption by the rat jejunum. Alterations in cytoskeletal functions are introduced by the administration of microfilamentous and microtubular altering agents such as cytochalasin, colchicine, or EDTA. An isolated jejunal segment perfused with a buffer containing labeled butyric acid was homogenized at the end of the experiment and assayed for its butyric acid content. During the perfusion, portal blood samples, as well as perfusate samples collected 10cm distal to the perfusion site were drawn at 5-min intervals and assayed for their radioactivity. Cytochalasin was found to decrease the permeability of the mucosal membrane to butyric acid and to increase that of the serosal membrane. Colchicine did not have any effect either on the mucosal or on the serosal side. Cytochalasin and colchicine, when given in the same experiment, increased the permeability of the serosal membrane to butyric acid, but were without any effect on the mucosal barrier. Also, EDTA had no effect on the mucosal side, but decreased significantly the permeability of the serosal membrane to the fatty acid.

Possible Modification of the Blood-Vitreous Humor Barrier of the Eye with Electromagnetic Energy

The eye is derived from neuroectoderm, as is the brain. Lt. bus blood barriers much like the blood-brain barrier, i.e., the blood-aqueous humor barrier and the blood-vitreous humor barrier. the blood-vitreous barrier is important inasmuch as it regulates the composition of the vitreous humor and is involved in controlling the ionic and metabolic environment of the retina. In viow of the apparent effect of microwave energy exposim- on the blood-brain barrier or something involving it, the common derivation and function of the blood-brain barrier and blood-vitreous barrier, and the sensitivity of the flurescein tracer technique as used with the eye, we used the fluorescein technique to explore the effect of microwave energy exposure on the blood-vitreous humor barrier of the eye. Rats were ox posed to low-intensity pulsed 1.2 GHz microwave energy which induced a uiifi 11 but significant increase in vitreous humor fluorescence. Apparently something involving the blood barriers is influenced by microwave energy exposure.

Time course of visceral edema in experimental burn trauma

Information on the time course of disturbances of water and electrolyte balance and the development of edema in various organs and tissues in burns is still very contradictory [4, 5]. The aim of the investigation described below was a quantitative study of disturbances of the water content of organs and tissues connected with structural changes in tissue--blood barriers after severe burn trauma. The water content was studied by the proton magnetic relaxation method [9]. The proton spin-lattice relaxation time (T:) was measured; its value in the cells and tissues characterizes mainly the mobility of protons of water molecules; the higher the water content, the higher the value of T:. An increase in TI in the liver and kidneys in rats and mice with deep burns (5-7% of the body surface) was demonstrated previously [i, 7]. To study the state of structures of the microcirculation, an electron-microscopic investigation of the organs was undertaken.

Blood barriers in the nervous system studied with horseradish peroxidase

The introduction of horseradish peroxidase (HRP) as a tracer which can be used in both light and electron micrograph studies of vascular permeability has been a major advance over previous tracer methods using mainly dyes and fluorescent substances. While confirming the existence of the blood-brain barrier (BBB) the high resolution of HRP has led to the identification of the sites of this barrier at specialized junctions between endothelial cells of brain capillaries. It is also clear from HRP tracer studies that many parts of the nervous system lie ‘outside’ the BBB and as a consequence may escape its protective function.

Permeability of tissue-blood barriers of the small intestine during perfusion with certain preservative solutions

The effect of some preservative solutions on changes in permeability of tissue—blood barriers of isolated loops of small intestine was studied in laboratory albino rats during perfusion of their vessels with 0.85% sodium chloride solution, with Ringer-Locke, Hanks', and Collins-2 solutions, and with the Soviet preparations Gemodez and Aminopeptid. The volume of fluid flowing from the vessels, penetration of perfusion fluid into the lumen of the intestine, and its elimination through the serous membrane were determined. It was concluded that the least disturbance to the tissue—blood barriers of the small intestine is observed during perfusion of its vessels with Collins-2 solution. This method is recommended as a test for comparing the properties of presservative solutions.

Fluid formed by choroid plexus; a technique for its collection and a comparison of its electrolyte composition with serum and cisternal fluids.

ArticlesFLUID FORMED BY CHOROID PLEXUS: A TECHNIQUE FOR ITS COLLECTION AND A COMPARISON OF ITS ELECTROLYTE COMPOSITION WITH SERUM AND CISTERNAL FLUIDSJacques de Rougemont, Adelbert Ames III, Frances B. Nesbett, and Helmut F. HofmannJacques de Rougemont, Adelbert Ames III, Frances B. Nesbett, and Helmut F. HofmannPublished Online:01 Sep 1960https://doi.org/10.1152/jn.1960.23.5.485MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByFluid transport in the brainMartin Kaag Rasmussen,* Humberto Mestre,* and Maiken Nedergaard1 March 2022 | Physiological Reviews, Vol. 102, No. 2Choroid plexus epithelial cells express the adhesion protein P-cadherin at cell-cell contacts and syntaxin-4 in the luminal membrane domainInga Baasch Christensen, Esben Nees Mogensen, Helle Hasager Damkier, and Jeppe Praetorius1 May 2018 | American Journal of Physiology-Cell Physiology, Vol. 314, No. 5Transport across the choroid plexus epitheliumJeppe Praetorius and Helle Hasager Damkier1 June 2017 | American Journal of Physiology-Cell Physiology, Vol. 312, No. 6Role of choroid plexus in cerebrospinal fluid hydrodynamicsNeuroscience, Vol. 354Directional Fluid Transport across Organ–Blood Barriers: Physiology and Cell Biology21 December 2016 | Cold Spring Harbor Perspectives in Biology, Vol. 9, No. 3Reply to Orešković et al.Helle H. Damkier, Peter D. Brown, and Jeppe Praetorius14 September 2016 | Physiological Reviews, Vol. 96, No. 4Cerebrospinal Fluid Secretion by the Choroid PlexusHelle H. Damkier, Peter D. Brown, and Jeppe Praetorius1 October 2013 | Physiological Reviews, Vol. 93, No. 4Epithelial Pathways in Choroid Plexus Electrolyte TransportHelle H. Damkier, Peter D. Brown, and Jeppe Praetorius1 August 2010 | Physiology, Vol. 25, No. 4Cytochemical study on enzyme activity associated with cerebrospinal fluid secretion in the choroid plexus and ventricular ependymaBrain Research, Vol. 222, No. 2Uptake and metabolism of cyclic AMP in rabbit choroid plexus in vitroNeuropharmacology, Vol. 16, No. 2The effect of pressure on the production of cerebrospinal fluid by the choroid plexusJournal of the Neurological Sciences, Vol. 16, No. 1Einige Feinstrukturbefunde an den Plexus chorioidei von AffenZeitschrift f�r Zellforschung und Mikroskopische Anatomie, Vol. 134, No. 4Effect of spinal fluid pressure on cerebrospinal fluid formationExperimental Neurology, Vol. 32, No. 1Cooperative phenomena in the permeation of sugars through the lining epithelium of choroid plexusBrain Research, Vol. 19, No. 3Cerebral Blood Flow In Man at High AltitudeCirculation Research, Vol. 19, No. 2 More from this issue > Volume 23Issue 5September 1960Pages 485-495 https://doi.org/10.1152/jn.1960.23.5.485PubMed13743963History Published online 1 September 1960 Published in print 1 September 1960 Metrics