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Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

160 records · Page 9Linked to original sources
PubMed1974

The development of a blood-brain barrier mechanism in foetal sheep.

1. The penetration of a metabolically inert, small molecular radius lipid insoluble substance ([(13)C] and [(4)H]sucrose), from blood into brain and c.s.f., has been studied in developing sheep from 50 days gestation (term, 150 days) through to the new-born stage. Around 50 days gestation sucrose accumulated rapidly into brain and c.s.f., and reached a steady-state level in brain of about 12% of the plasma level by 3 hr. By 60 days sucrose penetrated less freely into brain and c.s.f.; the brain steady-state level was 10% by 4(1/2) hr. A large decrease in sucrose penetration occurred by 70 days gestation, and by 123 days (just before the time when a foetal lamb becomes viable) both the rate of penetration and the brain steady-state level of sucrose were similar to those of the adult of other species.2. The rate of c.s.f. secretion at different ages has been estimated by dye dilution during ventriculo-cisternal perfusion. The turnover of c.s.f. in 60 day foetuses was high (1.36%/min.g wet weight brain). From 123 days gestation to the adult stage the turnover was much lower, 0.02%/min.g at 123 and 137 days gestation and 0.01%/min.g in the adult ewe.3. A simple new method for measuring c.s.f. volume is described. The volume at 51 days was estimated to be 0.14 ml., S.E. +/- 0.03, n = 4 (brain weight = 0.87 g +/- 0.11), at 59 days it was 0.45 ml., S.E. +/- 0.04, n = 6 (brain weight = 2.0 g +/- 0.1) and near term it was 7.28 ml S.E. +/- 1.29, n = 4 (brain weight 42.0 g +/- 0.5).4. The results are discussed in relation to possible changes in permeability of the cerebral capillary endothelium, the sink effect of c.s.f., and changes in extracellular space of the brain during its development. It is concluded that the high rate of penetration and raised brain steady-state level of sucrose in immature sheep foetuses is probably due to immaturity of a permeability barrier at the level of the cerebral capillary endothelium or its associated glial processes. Some clinical implications of these findings are considered briefly.

Animals↗
PubMed1974

An outflow of acetylcholine from normal and regenerating ventral roots of the cat.

1. An outflow of acetylcholine (ACh) has been measured from cat ventral roots in situ and in vitro, using standard bio-assay techniques. The ACh was collected in chambers, filled with physiological solution containing anticholinesterase, which surrounded the root.2. The outflow fell rapidly at first and then progressively more slowly, taking several hours to fall to a level near the assay threshold. The outflow of ACh resulted from cutting a root or from such conventional manipulations as stretching the root or teasing apart root filaments. The outflow could occur either from the end of a root (following cutting) or from along the length of the root (following stretching or teasing). The outflow was only detected in the presence of an anticholinesterase.3. ACh was resynthesized by roots at a rate which was usually rapid enough to maintain their ACh content at its original level in spite of a considerable ACh outflow. In roots subjected to a minimum of interference their ACh content built up to about twice the initial content after 5-7 hr soaking in eserinized Krebs solution although the total ACh outflow was equivalent to the original ACh content.Roots which were cut or stretched several times within a few hours put out a large amount of ACh and showed a fall in their ACh content below the initial level.4. The time course of sealing of the damaged ends of axons following crushing was assessed by measuring the injury potential for 1-2 hr after crushing at room temperature; in normal roots the half-time for decline of the injury potential was 91 +/- 10 min. This was slower than the rate of decline of the ACh outflow.5. An explanation for the observed outflow of ACh is discussed in terms of diffusion of ACh and sealing of axon ends. It is concluded that much of the ACh in normal ventral root axons is present in a readily diffusible form.6. Similar experiments on roots regenerating 9-10 days after crushing showed that the ACh outflow from regenerating roots was much smaller than from normal axons, although their ACh content was similar. This could have been due to more rapid sealing of the cut regenerating axons since the half-time for the decline of the injury potential following crushing of the regenerating axons was less than half that in control roots. The alternative possibility is considered that a high proportion of the ACh might be much less diffusible than in normal axons.7. The subcellular distribution of ACh in normal and regenerating peripheral axons is discussed.

Acetylcholine↗
PubMed1972

Electrolytes and water in the brain and cerebrospinal fluid of the foetal sheep and guinea-pig.

1. Samples of cisternal cerebrospinal fluid (c.s.f.) and blood plasma have been obtained nearly simultaneously from foetal sheep of different ages, the foetus having been exteriorized and maintained in a normal state with respect to its blood gases and arterial pH. The brains were removed from these foetuses and also from foetal guinea-pigs after exsanguination.2. A comprehensive study has been made of the concentrations of water, chloride, sodium, potassium, calcium and magnesium in blood plasma, c.s.f. and brain from foetal sheep and in brain from foetal guinea-pigs during development in utero. Maternal arterial blood plasma, cisternal c.s.f. and brain from the sheep and brain from the guinea-pig have been analysed for comparison.3. Concentrations of the ions analysed in foetal blood plasma are similar to those found by others in the sheep and other species. In the case of calcium, the results suggest an active maintenance of the concentration of this ion in foetal plasma by the placenta.4. The chloride concentration in c.s.f. at ages between 65 days and term (147 days) averaged 1.19 times that in foetal plasma, but only 1.08 at 45-50 days; the sodium concentration in c.s.f. was also slightly reduced at this time. The increase in the c.s.f./plasma ratios for chloride and sodium appears to coincide with the first development of the blood-brain and blood-c.s.f. barriers to non-electrolytes.5. Magnesium was at a slightly higher concentration in c.s.f. than in plasma at all foetal ages and did not vary with age. The concentrations of potassium and calcium in c.s.f. were high at early ages and fell to reach adult concentrations after birth: the mechanisms determining the concentrations of the various ions in c.s.f. develop at very different, largely independent, rates.6. The water content of the cerebral hemispheres of the foetal sheep was stable at 90% of the wet weight till 105 days and fell thereafter. The contents of chloride, sodium and potassium followed paraboloid relations with age. Chloride and sodium reached a peak of 62 and 81 m-equiv/kg respectively between 89 and 105 days in the sheep. Potassium was at a minimum of 65 m-equiv/kg at the same time. The content of water and these electrolytes in the cerebral hemispheres of the foetal guinea-pig underwent similar changes, the maxima and minimum occurring as in the sheep at two-thirds of the total length of the pregnancy, namely 65 days in the guinea-pig. At 46 days in the guinea-pig, chloride in brain reached 53 m-equiv/kg, sodium was 68 m-equiv/kg and potassium was 75 m-equiv/kg. In contrast to the sheep, no reversal of the sodium-potassium ratio occurred. These changes in water and electrolytes probably represent a rise, a peak and a decrease in the volume of the extracellular space of cerebral cortex, but changes in the volume occupied by a cell-type, containing much intracellular chloride and sodium, could also contribute to this phenomenon.7. The calcium content in the cerebral hemispheres of the foetal sheep remained at about 3.0 m-equiv/kg throughout pregnancy. Magnesium in the cerebral hemispheres of both the foetal sheep and the guinea-pig showed a trough in concentration during pregnancy which corresponded approximately in position to the minimum in potassium content and the maxima in chloride and sodium contents. Lowest values were 9.6 m-equiv/kg at 105 days in the sheep and 9.5 m-equiv/kg at 51 days in the guinea-pig.

Animals↗
PubMed1967

The distribution of acetylcholine in normal and in regenerating nerves.

1. The distribution of acetylcholine (ACh) in various nerves which had been regenerating for different periods after crushing has been compared with that in uncrushed nerves.2. Normal ventral roots from cats contained 78.1 +/- 22.7 (S.D.) mumole ACh/kg (blotted wet wt.); rabbit ventral roots contained 48.0 mumole/kg +/- 19.0 (S.D.) and rabbit sciatic nerves 16.6 +/- 7.3 (S.D.) mumole/kg. In the sciatic nerves the distal cm of 5 cm lengths taken from the thigh contained 30% more ACh than the most central cm portion. Possible explanations for this difference have been discussed.3. After both sciatic nerves and ventral roots had been crushed, there was an initial build-up (4 times control) of ACh central to the lesion and a decline ((1/4) control) distal to the lesion. These changes were maximum around 5 days after crushing. In sciatic nerves in which long periods of regeneration were investigated, the central build-up fell off to 1(1/2) times control by 25 days and the distal decline reversed to 2 times control in about 10 days. It then again decreased towards the control level by 25 days after crushing. These changes have been discussed in relation to the morphological changes which occur in a nerve following crushing.4. A peak of ACh content moved distally along the nerve from the crushed region at a rate of 1.0-1.5 mm/day. This was considered to represent an average rate of regeneration of the bulk of the axons. The amplitude of the peak declined progressively with time in the more distal parts of the nerve, probably because of dispersion as axons regenerated at different rates.

Acetylcholine↗
PubMedDate not supplied

Chicken GnRH II occurs together with mammalian GnRH in a South American species of marsupial (Monodelphis domestica).

Two molecular forms of gonadotropin-releasing hormone (GnRH) were demonstrated in hypothalamic extracts of M. domestica using high performance liquid chromatography and radioimmunoassay with specific GnRH antisera. One form eluted in the same position as synthetic mammalian GnRH and was quantified equally by two mammalian GnRH antisera, while the second form coeluted with synthetic chicken GnRH II and was quantified equally with two chicken GnRH II antisera. The finding of chicken GnRH II in a South American species of marsupial, which has previously been reported in some Australian species of marsupial and in species of Aves, Reptilia, Amphibia, Osteichthyes and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH.

Amino Acid Sequence↗
PubMedDate not supplied

The development of the human blood-brain and blood-CSF barriers.

The commonly held belief that the fetal blood-brain and blood-CSF barriers are immature is reviewed. Results obtained from carefully conducted experiments with horseradish peroxidase and optimal freeze-fracturing suggest that the chick, rat and monkey brain barrier systems to proteins are tight from the earliest stages of development. Previous studies are reviewed in the light of new information on retrograde axonal transport, circumventricular organs, the proper use of horseradish peroxidase, freeze-fracturing, immunocytochemistry and plasma protein gene expression in the developing human brain. Original data on the development of human brain barrier systems are included. Tight junctions between cerebral endothelial and choroid plexus epithelial cells form the morphological basis for these systems. CSF in the fetus contains a remarkably high concentration of protein in contrast to adult CSF which is characterized by a very low protein concentration. This has previously been interpreted as due to immaturity of barriers in the fetal brain. Tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells have been investigated in human embryos and fetuses by freeze fracture and thin section electron microscopy. As soon as the choroid plexus and the brain capillaries differentiated they exhibited well formed tight junctions. These junctions were very complex at early stages of development. A new barrier consisting of 'strap junctions' was found in the developing germinal matrix. The very high concentration of protein in early human fetal CSF cannot be accounted for by a lack of tight junctions in the developing brain barrier systems. Some transfer of proteins from blood to CSF, possibly via an intracellular route, has been demonstrated in immature experimental animals, but it seems that an important contribution to CSF proteins in the fetus may be synthesis by the developing brain and choroid plexuses with subsequent release into the CSF.

Biological Transport↗
PubMedDate not supplied

alpha 2HS-glycoprotein is expressed at high concentration in human fetal plasma and cerebrospinal fluid.

The concentration of alpha 2HS-glycoprotein (alpha 2HS), a human homologue of the fetal protein fetuin, has been measured in plasma and cerebrospinal fluid (CSF) of fetuses from 14 to 37 weeks of gestation and in cord blood from newborn babies. The levels were highest in both plasma and CSF in the younger fetuses, but even in the newborn the concentration of alpha 2HS in plasma was nearly twice the adult level. Two of six fetuses in the 14- to 19-week group had levels of alpha 2HS over 200 mg/100 ml, which is similar to the levels of fetuin in some fetal animals.

Adult↗