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H F Cserr

Publications and source records attributed to H F Cserr.

At least 37 records · Page 2Linked to original sources

Brain ion and volume regulation during acute hypernatremia in Brattleboro rats.

Regulation of brain ions and volume in response to 30 min of hypernatremia has been studied in two strains of anesthetized rats, the vasopressin-deficient Brattleboro and its vasopressin-competent parent strain, the Long-Evans. Plasma [Na] was increased by intraperitoneal injection of hyperosmolal NaCl. Brain volume was regulated during hypernatremia associated with tissue uptake of Na and Cl in both strains, but osmotically stimulated uptake of Na was 61% less in the Brattleboro. Blood-to-brain transfer constants for 22Na, measured as a function of plasma osmolality, were similar in the two strains. In contrast, bulk flow of cerebrospinal fluid (CSF) into brain, induced by osmotic dehydration of brain, was 55% less in the Brattleboro. CSF secretion in unstressed animals was also reduced, by 34%, in the Brattleboro compared with the Long-Evans. Reduced Na uptake by the brain of the Brattleboro rat during hypernatremia can be explained on the basis of a three-compartment model of brain volume regulation. Results support a function for vasopressin in brain ion homeostasis.

Acute Disease↗

Brain and cerebrospinal fluid ion composition after long-term anoxia in diving turtles.

Prolonged anoxia in turtles is associated with marked disturbances in plasma composition. This study examines brain and cerebrospinal fluid (CSF) ion homeostasis in the freshwater turtle, Chrysemys picta bellii, in response to 8-10 days of submergence anoxia at 10 degrees C. For comparison, it also examines the response to experimental elevation of plasma [K], [Ca], and [Mg] in normoxic turtles. Long-term anoxia resulted in marked changes in brain and CSF composition. These included elevated [K], [Ca], [Mg], and [lactate] and reduced [Cl], and the composition of CSF approached that of plasma. Brain water content increased by 17%, which we suggest was an intracellular edema linked largely to an 11% increase in total brain K. In contrast to the lack of effective homeostasis during anoxia, CSF composition was controlled in normoxic animals. We conclude that there is homeostasis of K, Ca, and Mg in the extracellular fluids of normoxic turtle brain, as in other vertebrates, but that this homeostasis fails during long-term anoxia.

Animals↗

Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia.

This study quantitatively evaluates the contribution of tissue Na, Cl, and K loss to brain volume regulation during acute dilutional hyponatremia (DH) and examines the mechanism of Na loss. DH was produced in pentobarbital sodium-anesthetized rats by intraperitoneal infusion of distilled water and brain water and electrolytes analyzed 30 min, 1 h, 3 h, 4 h, or 6 h later. The rate of Na and Cl loss was greatest during the first 30 min of DH (0.43 and 0.47 meq X kg tissue dry wt-1 X min-1, respectively). Net loss of Na and Cl was maximal after 3 h of DH. K loss was slower, achieving significance after 3 h. Electrolyte loss was sufficient to account for observed brain volume regulation after three or more hours of DH. Measurements of 22Na influx and efflux across the blood-brain barrier showed that barrier permeability to Na is unchanged during DH. Analysis of results using a two-compartment model of plasma-brain exchange suggests that loss of brain Na during DH does not result solely from a shift of electrolyte across the blood-brain barrier to plasma, and thus provides indirect evidence for an additional pathway for Na loss, presumably via cerebrospinal fluid.

Animals↗

Regulation of brain water and electrolytes during acute hyperosmolality in rats.

Regulation of brain water and electrolytes during acute hyperosmolal states has been studied in anesthetized rats. Rats were injected intravenously or intraperitoneally with hypertonic NaCl, mannitol, or sucrose (hyperosmolal series) or with isotonic NaCl (isosmolal controls). Terminal plasma osmolality varied from 290 to 385 mosmol/kg and the experimental duration from 15 to 120 min. Osmotically induced water loss from brain tissue for the different protocols was only 26-78% of that predicted for ideal osmotic behavior, revealing a degree of tissue volume regulation, and the brain gained Na, Cl, and K. This gain was sufficient to account quantitatively for tissue volume regulation at 120 min of hypernatremia but not at shorter times or during mannitol- or sucrose-induced hyperosmolality. Water loss and electrolyte uptake occur simultaneously, over 30 min, which limits the degree of brain shrinkage. Results of this analysis of the time course and magnitude of tissue electrolyte gain during acute hyperosmolality form the basis for the following two studies of the volume regulatory influx of electrolyte from plasma and CSF, respectively.

Animals↗

Volume regulatory influx of electrolytes from plasma to brain during acute hyperosmolality.

Brain volume is regulated during acute hyperosmolal states based, in part, on the tissue gain of Na, Cl, and K [H. F. Cserr, M. DePasquale, and C.S. Patlak, Am. J. Physiol. 253 (Renal Fluid Electrolyte Physiol. 22): F522-F529, 1987]. This study evaluates the contribution of influx from plasma to the volume regulatory gain of electrolyte. Blood-to-brain transfer constants, K1, were measured as a function of plasma osmolality, over the range 300-385 mosmol/kg, for sodium (22Na) and potassium (42K or 86Rb) and as a marker for nonselective changes in permeability for [14C]mannitol. Osmolality was elevated by intraperitoneal injection of hypertonic NaCl, mannitol, or sucrose. K1 for Na, K, and mannitol each increased linearly with plasma osmolality. Increases in K1 for Na and mannitol were small and were proportional to their respective diffusion coefficients, consistent with the development of a small leak pathway. Increases in K1 for K were much larger, consistent with osmotic stimulation of a selective permeability pathway. Quantitative analysis of the results suggests that uptake from plasma accounts for most of the K gained by brain tissue in response to acute hyperosmolality but for only a small fraction of the Na. This provides indirect evidence for an additional source of Na, presumably from cerebrospinal fluid.

Animals↗

Bulk flow of cerebrospinal fluid into brain in response to acute hyperosmolality.

Brain volume is regulated during acute hyperosmolality based, in part, on the tissue gain of Na, Cl, and K. This study evaluates the contribution of bulk flow of cerebrospinal fluid (CSF) into brain to the volume regulatory gain of electrolytes. Artificial CSF containing radiolabeled albumin and diethylenetriamine penta-acetic acid (DTPA) was perfused for 60 min through the ventricles and/or subarachnoid space of anesthetized rats, and tracer clearances from CSF to brain were measured as a function of plasma osmolality. Osmolality was elevated after 30 min of perfusion by intraperitoneal injection of hypertonic NaCl or mannitol. Albumin and DTPA clearances increased with osmolality at the same rate, despite a sevenfold difference in diffusion coefficient, consistent with osmotic stimulation of a bulk flow component of tracer influx into brain. The volume shift estimated on the basis of this data is 114 microliters CSF/g dry wt brain for a 60-mosmol/kg increase in osmolality. Results indicate that CSF is a major source of the volume regulatory gain of Na and Cl, but not of K.

Animals↗

Increased permeability of a glial blood-brain barrier during acute hyperosmotic stress.

Brain volume is regulated during acute hypernatremia in the little skate, Raja erinacea, based on the gain of osmolytes, including sodium, chloride, and potassium [Cserr et al., Am. J. Physiol. 245 (Regulatory Integrative Comp. Physiol. 14): R853-R859, 1983]. In this study we show that this volume regulatory response is complete in 35 min and examine the mechanism of sodium influx across the blood-brain barrier over this period. Skates have a glial blood-brain barrier. Blood-to-brain transfer constants (K1) for 22Na and [14C]mannitol were measured using the integral technique of [Ohno et al.Am. J. Physiol. 235 (Heart Circ. Physiol. 4): H299-H307, 1978]. In skates injected intramuscularly with isotonic saline (controls) or with hypertonic NaCl or fructose, K1 for sodium increased linearly with osmolality. This increase was the same for hypernatremia and fructose-induced hypertonicity, and it was not affected by the "loop" diuretic bumetanide. K1 for mannitol also increased with osmolality. These results suggest that hypertonicity increases barrier permeability by a nonselective mechanism. The contribution of influx across the blood-brain barrier to tissue sodium gain during acute hypernatremia is assessed using a diffusional model of plasma-brain exchange.

Animals↗

Brain vascular volume, electrolytes and blood-brain interface in the cuttlefish Sepia officinalis (Cephalopoda).

Cephalopod molluscs have complex brains and behaviour, yet little is known about the permeability of their blood-brain interface. This paper presents studies on the brain fluid and electrolyte compartments of the cuttlefish Sepia, as a preliminary to characterization of the permeability of the blood-brain interface in this group. Sepia is shown to be a satisfactory experimental animal, and techniques are described for anaesthesia, cannulation, and tissue and fluid analysis. Our ionic analyses of body fluids are in general agreement with those of earlier workers. Analysis of brain tissue suggests that the extracellular space is 17-20 ml 100 g tissue-1 (i.e. 17-20%). Two large molecular weight tracers, 125I-human serum albumin (HSA) and Blue dextran, give consistent values for the brain vascular volume of 3.5-5.5%, slightly higher than in vertebrates. The HSA results further confirm that the Sepia blood-brain interface is relatively tight to proteins. Finally, we have shown that the fluid surrounding the brain, pericerebral fluid (PCF), is in relatively free communication with plasma.

Animals↗

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↗

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↗

Drainage of interstitial fluid from different regions of rat brain.

Studies were carried out in anesthetized rats comparing dynamics and pathways of interstitial fluid (ISF) drainage from different regions of brain. Rates of drainage from brain and flow into cerebrospinal fluid (CSF) were estimated from the efflux from brain and influx into CSF of radioiodinated albumin (RISA) following microinjection into caudate nucleus, internal capsule, or midbrain: pathways of flow through the subarachnoid space and into lymph were traced from the distribution of horseradish peroxidase and/or Evans blue-labeled albumin after injection into brain. ISF drainage rates (mul X g brain-1 X min-1) estimated for the three injection sites were 0.18, 0.19, and 0.29, respectively. Flow of ISF into bulk CSF sampled from the cisterna magna accounted for 60-75% of efflux from midbrain but only 10-15% of efflux from caudate nucleus or internal capsule. RISA was concentrated in the subarachnoid space, relative to bulk CSF, in sleeves of adventitial tissue surrounding pericerebral arteries, possibly accounting for the low recovery of isotope from bulk CSF. From the subarachnoid space, some fluid drained via olfactory nerve sheaths to retropharyngeal lymph nodes.

Animals↗

Control of extracellular ions in skate brain during osmotic disturbances.

Regulation of brain water and osmolytes in osmotic disturbances has been studied in the little skate, Raja erinacea. Free-swimming fish were subjected to seawater plus 125 mM NaCl (hyperosmotic; these also received 10 ml/kg body wt im 4.19 M NaCl in elasmobranch Ringer) or to 50% seawater (hyposmotic). At a set time, fish were killed, and blood and brain (telencephalon and medulla) were analyzed. Brain water was divided into a Cl- and a non-Cl- space. Responses of water and osmolytes to osmotic disturbances were mutually consistent. In telencephalon, there was good regulation of Cl- space, based on Na+ and Cl- shifts in hypo- and hyperosmolality. This control was near perfect at 2- and 4-h hyperosmolality. Regulation of non-Cl- space was minimal at 24-h hyperosmolality, with small K+ uptake. In medulla, Cl- space and ions were unregulated, whereas non-Cl- space was partly controlled in hyposmolality in relation to amino acid loss. Thus in this elasmobranch, regulation of Cl- space and of Na+ and Cl- is effective in telencephalon but is nonexistent in medulla oblongata.

Amino Acids↗

Impermeability of hagfish cerebral capillaries to radio-labelled polyethylene glycols and to microperoxidase.

The rate and extent of penetration of radiolabelled polyethylene glycols (900 and 4000 daltons) from plasma into brain was examined in the Atlantic hagfish (Myxine glutinosa), a primitive vertebrate, and, for comparison, in the rat. Tracer penetration into brain was limited to a similar extent in hagfish and in rats, indicating a basic similarity between the two species in the blood-brain barrier to polar non-electrolytes. The permeability of hagfish brain capillaries to the electron microscopic tracer microperoxidase (2000 Daltons) was also examined. Intravenously injected microperoxidase remained confined to the capillary lumen and was not found in the basal lamina or surrounding brain parenchyma. In contrast to an earlier study, these results indicate that the hagfish has a blood-brain barrier to hydrophilic molecules larger than 900 Daltons. It is concluded that a blood-brain barrier is a general characteristic of all vertebrates.

Animals↗

Efflux of radiolabeled polyethylene glycols and albumin from rat brain.

Experiments were carried out to evaluate the role of convection in the removal of large molecules from brain interstitial fluid. Radiolabeled test compounds were injected into the caudate nucleus of anesthetized rats through a guide cannula implanted 1 wk previously and the concentrations of isotope in brain and cerebrospinal fluid (CSF) determined at various times after injection. Control studies with 22Na indicate that the permeability of the blood-brain barrier is normal in tissue surrounding the intracerebral injection cannula. For 69,000 dalton serum albumin, 4,000 dalton polyethylene glycol, and 900 dalton polyethylene glycol, clearance from brain approximates a single exponential decay with half times of disappearance of 12.2, 12.6, and 14.4 h, respectively. Similarly in efflux rate, despite a fivefold difference in diffusion coefficient, is consistent with convective losses from brain, and the maximal rate of interstitial fluid removal estimated on the basis of these data is 0.11 microliter.g brain-1.min-1. Only 10-20% of total efflux is into bulk CSF withdrawn from the cisterna magna.

Animals↗