PubMed Health⌕ Search

Biomedical subjects

M Bundgaard

Publications and source records attributed to M Bundgaard.

At least 37 records · Page 2Linked to original sources
PubMed1985

Tightness of the blood-brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis.

Cephalopod molluscs have complex brains and behaviour, yet little is known about the permeability of their blood-brain interface. The accompanying paper characterized the fluid compartments of the brain and presented evidence for restricted permeability of the blood-brain interface to albumin. The present paper investigates the permeability of the interface to small non-electrolytes. [14C]Polyethylene glycol (PEG, mol. wt. 4000), and [51Cr]EDTA (mol. wt. 342) were injected intravenously or intramuscularly, and their penetration into brain and muscle studied up to 48 h. Tracers equilibrated with muscle interstitial fluid (ISF) at relatively short times, but in brain ISF reached only 0.5-0.65 X their plasma concentration. This is qualitative evidence for the presence in brain of a barrier to these molecules and an efficient drainage mechanism for ISF. Quantitative treatment of the uptake data allows calculation of the permeability X surface area product (PS) and the permeability coefficient (P). For the brain PS and P are in the range 1-3 X 10(-4) ml g-1 min-1 and 1-3 X 10(-8) cm s-1 respectively, (PEG), and 3 X 10(-4) ml g-1 min-1 and 3-4 X 10(-8) cm s-1 respectively (Cr-EDTA). The P values are close to those reported for mammalian brain. Assuming that the lack of equilibration in brain is due to ISF flow, the rate of flow can be calculated. Values for vertical and optic lobe are approximately 0.2 microliter g-1 min-1, again close to those reported for mammalian brain. It is concluded that the tightness of the Sepia blood-brain barrier approaches that of mammals, and a flowing ISF system is present. An association between a tight barrier and higher central nervous system integrative function is suggested. The significance of these findings for the evolution of control of the brain microenvironment is discussed.

Animals↗
PubMed1984

Identification of free coated pinocytic vesicles in Swiss 3T3 cells.

Whether or not free coated vesicles are involved during internalization of ligands bound to the receptors of coated pits is controversial. Free coated vesicles cannot be identified with certainty in random individual thin sections - reconstructions based on consecutive thin sections are required. The thickness of the sections determines the reliability of such reconstructions. In the present study, serial section electron microscopy was applied to Swiss 3T3 cells and the topographical resolution yielded by 80 nm and 20 nm sections was compared. Swiss 3T3 cells in monolayer at 37 degrees C were exposed for 5 min to cationized ferritin (CF) which is a marker of pinocytic vesicles. Subsequently the cells were fixed, pelleted and further processed for electron microscopy. The results showed that reconstructions of coated CF-labeled structures based on consecutive sections of an average thickness of approximately 80 nm could not be performed with certainty. A substantial fraction (25%) of the examined profiles appeared to be free vesicles, but narrow surface connections could easily have been missed in these thick sections. The series of the much thinner 20 nm sections provided a better resolution allowing the narrowest surface connections to be identified. Accordingly, the number of truly free, coated vesicles was much lower than the number of apparently free vesicles in the thick sections. However, free coated vesicles labeled with CF were identified in the consecutive 20 nm sections (4% of the examined profiles).

Animals↗
PubMed1984

Permeabilities of single arterioles and venules in the frog skin: a functional and morphological study.

The permeability of single subcutaneous microvessels in the frog skin was determined with electrophysiological techniques after only minimal surgical intervention. The organization of blood vessels in the frog skin is described at the microscopic level. Transmission electron microscopy showed that the subcutaneous microvessels belong to the class of "continuous" vessels (H. Bennett, J. Luft, and J. Hampton, 1959, Amer. J. Physiol. 196, 381-390). Capillaries in the true sense of the word are rare in this subcutaneous tissue. The electrical resistance of the endothelium in well defined segments of the subcutaneous microvessels was determined by means of current injection and voltage recording microelectrodes using cable theory for the analysis. The average resistances were 70 and 24 omega.cm2 for arterioles and venules, respectively; the mean values of the two groups were significantly different (P less than 0.001). These figures are close to those obtained on microvessels in skeletal muscle (S.-P. Olesen and C. Crone, 1983, Biophys. J. 42, 31-41), but are about one order of magnitude higher than resistances of mesenteric microvessels. The calculated sodium permeabilities were for arterioles: PNa+ = 1.6 x 10(-5) cm sec(-1) and for venules: 4.6 x 10(-5) cm sec(-1).

Animals↗
PubMed1984

The three-dimensional organization of tight junctions in a capillary endothelium revealed by serial-section electron microscopy.

Estimates of capillary permeability for hydrophilic solutes are generally interpreted in terms of Pappenheimer's pore theory. The intercellular clefts of the capillary endothelium are considered a likely structural equivalent to the postulated system of small hydrophilic pores. However, correlation of permeabilities and cleft structure requires more knowledge of the detailed structure of the tight junctions which appear to obliterate the clefts. In this study the organization of tight junctions in endothelium of rat heart capillaries has been investigated by serial-section electron microscopy. Cross-sectioned intercellular clefts were photographed in a series of 190 consecutive sections (average thickness approximately equal to 40 nm) and in a series of 16 consecutive sections (average thickness approximately equal to 12.5 nm). Seventy-one junctional segments, each extending over 5-32 consecutive sections, were reconstructed. The endothelial junctions were organized as irregular networks of lines of contact between neighboring cells. Six pathways circumventing the lines of contact were followed through the entire junctional region of the clefts providing a tortuous pathway connecting the luminal and abluminal aspects of the clefts. Moreover, the individual lines of contact were provided with discrete discontinuities, apparently 4 nm wide. The observations support the notion that the paracellular pathway in capillary endothelium is permeable not only to small solutes but also to certain macromolecules.

Animals↗
PubMed1984

Blood-brain interfaces in vertebrates: a comparative approach.

The neuronal microenvironment in the vertebrate brain is isolated from plasma by a series of selective membranes, including the blood-brain barrier, the choroid plexus, and the meningeal barrier. This review deals with the structure and function of these selective membranes in the different vertebrate classes. Present knowledge indicates that all vertebrates have brain barrier membranes and, further, that functional characteristics of these membranes are basically similar in all the vertebrate classes. The blood-brain barrier (or capillary-glial complex) and the meningeal barrier have many of the properties of a tight epithelium, including the presence of tight junctions and specific transport mechanisms. The choroidal epithelium is a typical secretory epithelium. The functional significance of the specialized membranes located at the blood-brain interface is considered, and we suggest that the phylogenetic development of a blood-brain barrier provided neurons of the vertebrate brain with a unique extracellular milieu optimal both for synaptic communication and for nonsynaptic communication via the entire extracellular space.

Adaptation, Physiological↗
PubMed1983

Vesicular transport in capillary endothelium: does it occur?

A revised picture of the organization of endothelial plasmalemmal vesicles is presented. Three-dimensional reconstructions of endothelial segments from frog mesenteric capillaries and rat heart capillaries based on ultrathin serial sectioning have shown that plasmalemmal vesicles are not true vesicles but parts of an elaborate system of invaginations of the surface membrane. The revised picture probably applies to capillary endothelia in general. The absence of free cytoplasmic vesicles implies that vesicular transport is unlikely to occur. A reinterpretation of previous studies of vesicular transport shows that they are equally compatible with the present view that plasmalemmal vesicles are static elements of invaginations of the endothelial surface membrane.

Animals↗
PubMed1983

The three-dimensional organization of plasmalemmal vesicular profiles in the endothelium of rat heart capillaries.

The organization of plasmalemmal vesicular profiles in the endothelium of rat heart capillaries has been reinvestigated. Judged from random thin sections approximately 50% of the vesicles appeared free in the cytoplasm, the rest opening to the surfaces of the endothelial cells--a distribution which corroborates previous studies. However, three-dimensional reconstructions based on ultrathin serial sections (thickness congruent to 12 nm) gave a very different picture. All plasmalemmal vesicular profiles (921 from 5 capillaries) were parts of the surface membrane either as caveolae or as more complex racemose invaginations. This organization has previously been observed in frog mesenteric capillaries ((M. Bundgaard, J. Frøkjaer-Jensen, and C. Crone, 1979, Proc. Nat. Acad. Sci. USA 76, 6439-6442) and (J. Frøkjaer-Jensen, 1980, J. Ultrastruct. Res. 73, 9-20)). It is therefore proposed that absence or extreme rarity of free plasmalemmal vesicles is a general feature of capillary endothelia. Consequently, we suggest that the term "endothelial, plasmalemmal vesicles" be replaced by "endothelial plasmalemmal invaginations." The results imply that trans-endothelial vesicular transport is unlikely to occur and that this membrane system performs other--as yet unknown--functions.

Animals↗
PubMed1982

Ultrastructure of frog cerebral and pial microvessels and their impermeability to lanthanum ions.

Permeabilities of single pial microvessels in the frog are now being estimated. Fine structural information on these vessels will therefore be needed in attempts to correlate structure and permeability. Microvessels from the dorsal part of the telencephalon and from the overlying pial layer in the common frog (Rana temporaria) and their permeability to lanthanum ions were studied in the electron microscope. Extensive structural similarities between the endothelial lining of cerebral and pial microvessels were demonstrated, indicating similarity in functional characteristics. Adjacent endothelial cells in both categories of vessels were joined by elaborate tight junctions. Lanthanum ions did not permeate the endothelium. Diffusion of the ion in the interendothelial clefts was stopped by the junctions. It is concluded that the frog has an endothelial blood-brain barrier which is tight to lanthanum ions.

Animals↗
PubMed1982

Brain barrier systems in the lamprey. I. Ultrastructure and permeability of cerebral blood vessels.

It is unclear whether the lamprey (class: cyclostomes) has a blood-brain barrier as in other vertebrates. Therefore, the present study re-examined the lamprey blood-brain barrier. Brain capillaries in the lamprey (Lampetra fluviatilis), and their permeability to horseradish peroxidase (HRP; molecular weight 40,000) and microperoxidase (MP; molecular weight 2000) were studied in the electron microscope. All brain vessels were capillaries. Each capillary formed a single hairpin-like loop. Their endothelia contained vesicles and tubules which often opened to the surface, preferentially the abluminal. Tubules creating transendothelial channels were not observed. Adjacent endothelial cells interdigitated extensively. The intercellular cleft was obliterated by 2-7 punctate appositions or fusions of the membranes. Intravenously injected HRP and MP, which were allowed to circulate for up to 30 and 20 min, respectively, did not permeate the brain endothelium. Few endothelial vesicles or vacuoles were labelled by the tracers. In the intercellular clefts, reaction product was only observed in their luminal part. HRP injected into the brain ventricles permeated the ependyma and diffused into the brain intersitium. The tracer permeated the pericapillary sheath of glial cells and the endothelial basal lamina of the capillaries within this diffusion profile. Labelling of the cleft between adjacent endothelial cells was confined to their abluminal part. It is concluded that the lamprey has an endothelial blood-brain barrier to macromolecules.

Animals↗
PubMed1982

Brain barrier systems in the lamprey. II. Ultrastructure and permeability of the choroid plexus.

The lamprey choroid plexus was studied by electron microscopic techniques and the composition of cerebrospinal fluid and plasma compared as part of a characterization of the lamprey blood-brain barrier. It was shown that the ultrastructure of the lamprey choroid plexus is very similar to that of the mammalian plexus. A blood-cerebrospinal fluid (CSF) barrier to horseradish peroxidase (molecular weight 40,000) and microperoxidase (molecular weight 2000) was localized to apical tight junctions between the choroidal epithelial cells. Pinocytic uptake of the tracers took place particularly at the apical surface of the epithelium (after intravenous and intraventricular administration). Absorbed tracer-molecules were found in vacuoles presumably belonging to the well-developed lysosomal apparatus of the epithelial cells. Extended Golgi-complexes, dense bodies and some multivesicular bodies were reactive for acid phosphatase activity. Measurements of protein, potassium and sodium in plasma and CSF revealed the same concentration differences previously observed in higher vertebrates. The present study lends further support to the view that the lamprey blood-brain barrier is similar to that of higher vertebrates.

Acid Phosphatase↗
PubMed1982

The ultrastructure of cerebral blood capillaries in the ratfish, Chimaera monstrosa.

Sharks and skates (Chondrichthyes: Elasmobranchii) have a glial blood-brain barrier, while all other vertebrates examined so far have an endothelial barrier. For comparative reasons it is desirable to examine the blood-brain barrier in species from the other subclass of cartilaginous fish, the holocephalans. The ultrastructure of cerebral capillaries in the chimaera (Chondrichthyes: Holocephali) is described in the present study. The endothelial cells are remarkably thick. Fenestrae and transendothelial channels were not observed. The endothelial cells are joined by elaborate tight junctions. The perivascular glial processes are separated by wide spaces (15-60 nm) without obliterating junctional complexes. These findings indicate that the chimaera has an endothelial blood-brain barrier.

Animals↗
PubMed1982

Structure of Necturus gallbladder epithelium during transport at low external osmolarities.

Gallbladders transport isotonically over a wide range of osmolarities. This ability has been assumed to depend on the geometry of the lateral intercellular spaces. We report that this geometry in the Necturus gallbladder varies extensively with the external osmolarity and depends in vitro on the integrity of the subepithelial tissues. The structure of the living epithelium was studied by Nomarski light microscopy while ultrastructural effects were revealed by electron microscopy. The short-term effects (less than 60 min) of low external osmolarities were: 1) the cells became bell-shaped with an increased cell height measured centrally, 2) lateral intercellular spaces lost their convoluted character; and 3) numerous membrane-bound cavities appeared in the cells. Furthermore, long-term exposure to the low external osmolarities caused an uneven density of epithelial cells. With subepithelial tissues intact, blistering of the epithelium cell layer was evident. Qualitative electron-microscopic data indicate that the membrane of the cavities was recruited from the basolateral cell membrane. This agrees well with light-microscopic observation that the cavities were initiated as invaginations of this cell membrane.

Animals↗
PubMed1981

Localization of sodium pump sites in cat pancreas.

1. Cat pancreases were exposed to [3H]ouabain either by perfusion, or by incubation of slices, with Krebs--Henseleit bicarbonate solution containing [3H]ouabain, and [3H]ouabain binding sites were localized by light microscopical autoradiography. 2. Acinar cells were found to possess only a few [3H]ouabain binding sites located on the basolateral plasma membranes. 3. The epithelial cells lining the intercalated and interlobular ducts were heavily labelled. The [3H]ouabain binding sites were located on the basolateral membranes. 4. Since secretion of pancreatic juice can be abolished by ouabain, it is concluded that the duct cells, especially those of the numerous small (intercalated) and intermediate-sized (interlobular) ducts are responsible for pancreatic secretion of electrolytes and water. 5. The localization of the (Na+ + K+)-activated ATPase to the basolateral membranes of the cells excludes a direct role of the transport enzyme in the secretion of Na+. However, a model is proposed where the Na+ + K+)-activated ATPase plays a crucial, though indirect role in pancreatic secretion of electrolytes and water.

Animals↗
PubMed1981

Horseradish peroxidase and microperoxidase. Their purity and binding to serum proteins.

Buffer solutions of commercially available batches of the electron microscopic enzyme tracers, horseradish peroxidase (HRP, mol wt = 40,000) and microperoxidase (MP, mol wt = 2,000), were investigated by gel filtration. The elution profiles of the HRP and MP solutions together with estimates of the peroxidatic activity of the collected fractions indicated that HRP was homogeneous with respect to molecular weight, while MP contained high molecular weight impurities with peroxidatic activity. Serum samples from four different species of tracer-injected animals (hagfish, lamprey, frog, mouse) and from control animals were investigated with the same techniques. No binding between HRP and the serum proteins or degradation of HRP was detected; whereas, MP circulated predominantly bound to serum proteins in all the investigated animals. The number average molecular weights of aqueous solutions of HRP and MP determined by vapor osmometry were 9,000 and 1,000, respectively. The results emphasize that protein binding should be evaluated when MP is used as an electron microscopic tracer. In addition, the finding that HRP and MP solutions have a much higher osmotic activity than the molecular weights of the tracers would suggest should be taken into consideration, especially when bolus injections into animals are performed.

Animals↗
PubMed1980

ATP-dependent Ca2+ accumulation by microvesicles isolated from bovine neurohypophyses.

Microvesicles with and without coats were isolated from bovine neurohypophyses by a series of ultracentrifugation steps. They were similar to microvesicles previously isolated from brain. In the presence of ATP and Mg2+, the microvesicles accumulated calcium. Oxalate stimulated and the Ca2+ ionophore A23187 inhibited calcium accumulation. In the presence of Ca2+ and Mg2+ the microvesicles also demonstrated ATPase activity. As judged by SDS electrophoresis in polyacrylamide gels microvesicle protein composition was very different from that of neurosecretory granules, suggesting that they are not granule membranes "retrieved" after exocytosis. They may have an important function in regulation of Ca2+ ion concentration.

Adenosine Triphosphatases↗