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H C Jones

Publications and source records attributed to H C Jones.

At least 55 records · Page 3Linked to original sources

Effect of histamine and antagonists on electrical resistance across the blood-brain barrier in rat brain-surface microvessels.

The effect of histamine on blood-brain barrier permeability was investigated using in situ measurement of transendothelial electrical resistance in brain-surface microvessels of anaesthetized rats. Mean resistance of vessels superfused with artificial cerebrospinal fluid was 1500 omega.cm2, indicating a tight barrier with low ion permeability. The addition of 10(-4) M histamine resulted in a 75% decrease in resistance, in both arterial and venous vessels, indicating a marked increase in barrier permeability. To determine the nature of the response to histamine, rats were given presurgical intraperitoneal injections of promethazine (H1 receptor antagonist), cimetidine (H2 receptor antagonist) or indomethacin (cyclo-oxygenase inhibitor), singularly and in combinations. Cimetidine completely blocked the histamine-mediated increase in barrier permeability whereas promethazine only had a small effect and indomethacin was ineffective. In addition, cimetidine treatment resulted in a 100% increase in basal resistance in both arterial and venous vessels, suggesting endogenous histamine was acting to increase blood-brain barrier permeability. It is concluded that histamine causes an increase in blood-brain barrier permeability which is mediated via endothelial H2 receptors, and that the electrical resistance in cimetidine-treated rats most closely represents the true permeability of the blood-brain barrier.

Animals↗

MR imaging for measurements of ventricles and cerebral cortex in postnatal rats (H-Tx strain) with progressive inherited hydrocephalus.

As part of a wider investigation on brain structure and function in young rats with inherited hydrocephalus, this study was undertaken to develop a technique to monitor, and quantify, progressive changes in ventricle and cortical dimensions in hydrocephalic rats in vivo. Magnetic resonance images were obtained with a T1-weighted protocol and a multislice variant of the inversion recovery sequence which displayed optimal contrast between cerebrospinal fluid and brain parenchyma. Rats were imaged at 7, 14, and 21 days after birth by taking 10 contiguous 2.0-mm coronal slices. Area and distance measurements were taken from the displayed images, enabling calculation of ventricle volumes, cortical length, and cortical thickness. The lateral ventricle volume, which was already 100-fold larger than control at 7 days, increased to over 1000 mm3 at 21 days. The anterior-posterior length of the cortex was up to 27% larger in hydrocephalics and the cortical mantle was up to 75% thinner, particularly in the posterior cortex. Subsequent fixation and histological sectioning of two 21-day-old rats showed that the smaller dimensions, which were obtained from analysis of the sections, could be accounted for by shrinkage of the tissue during dehydration and wax embedding.

Aging↗

The cerebral cortex in congenital hydrocephalus in the H-Tx rat: a quantitative light microscopy study.

Hydrocephalus in the H-Tx rat first develops in late gestation and causes death at 4-7 weeks. The effect of hydrocephalus on overall cortical dimensions and on five specific regions (frontal, sensory-motor, parietal, auditory and visual) has been studied by quantitative light microscopy at 10 and 30 days after birth. The lateral ventricle volumes in hydrocephalic rats were about 40 x larger than controls and increased fourfold between 10 and 30 days. Cortical volume was reduced by a small amount at 10 days but was larger in hydrocephalics at 30 days. Thinning of the cortical mantle was severe with disruption of the laminar structure, particularly in the auditory and visual regions, where it was already present at 10 days. The density of cortical cells (neurones and glia) was not altered in hydrocephalics at 10 days but was reduced in all regions at 30 days. Estimates of total cell number suggest that the lower density was not associated with an overall loss of cells. Capillary numerical density was not affected by the hydrocephalus at 10 days after birth but by 30 days it was significantly lower, particularly in the worst-affected posterior regions. The results show that the cerebral cortex is severely distorted and that in advanced hydrocephalus, although overall cell number is not affected, both cell density and capillary density are lower by up to 30%.

Aging↗

Cerebrospinal fluid pressure in 10-day-old rats with congenital hydrocephalus.

Rats from the H-Tx strain develop hydrocephalus through a developmental obstruction of the cerebral aqueduct. The progressive ventriculomegally is accompanied by thinning of the cerebral cortex which is already present 10 days after birth. However, a previous study found that the CSF pressure was not significantly raised until 21 days after birth. New experiments have now been performed over a 90 min. period using control and hydrocephalic 10-day-old rats under light pentobarbitone anaesthesia, in order to study the level, time-course and morphology of the resting intraventricular pressure. The mean pressure and its fluctuations were calculated for each minute. Control rats had a mean pressure of 19.3 +/- 1.23 (SEM) mm H2O (n = 9, range: 13.6-24.7) and in hydrocephalic rats, pressure was significantly higher at 23.5 +/- 1.13 mm H2O (n = 9, range: 18.1-28.3). There was no consistent trend with time and no significant difference between groups in pressure fluctuations, but at least two of the hydrocephalic rats showed episodic waves similar to "B"-waves in humans.

Animals↗

A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the rat.

Morphometric changes in the rat lateral ventricle choroid plexus epithelium and endothelium and in the ventricular ependyma were studied between 16 days gestation and 30 days after birth, using stereological techniques. The epithelial apical surface density increased from 0.6 to 3.3 microns 2/microns 3 and the mitochondrial volume fraction from 3.2 to 7.6% during this period. The endothelial fenestrations increased from 0.05 to 0.39 micron-1. These changes may be related to postnatal increases in choroid plexus function. Morphological changes in basolateral surface density, cell height and nucleus and glycogen volume fraction have also been measured. The development of the lateral ventricle choroid plexus was qualitatively similar to the fourth ventricle plexus reported previously, but small quantitative differences occurred. The ventricular ependyma also showed a significant increase in mitochondrial volume fraction after birth, though to a lesser extent than the plexus epithelium. The total apical surface area of the choroid plexuses was estimated at 75 cm2 for 30-day-old rats. This figure, which takes into account the apical microvilli, is much greater than previous estimates and is similar to the surface area of the cerebral capillaries (155 cm2), and suggests that the choroid plexuses may play a more important role in the regulation of the brain microenvironment than previously thought.

Animals↗

Cortical microvessels during brain development: a morphometric study in the rat.

In order to determine whether any structural changes occur in the blood-brain barrier during development which can be related to changes in barrier function over the same period, morphometric methods were used on pieces of visual cortex taken from rats between 16 days gestation and adult and processed for light and electron microscopy. Capillary volume fraction, numbers per unit area, and surface density increased in two phases, before birth and between 10 and 20 days after birth, with no subsequent change after 20 days. Brain parenchymal mitochondria, assumed to be a measure of brain oxidative activity, did not change before birth but increased gradually and continuously after birth from 1.7% to 5.7% in adults. The capillary endothelial mitochondrial volume fraction as a percentage of the endothelial cell cytoplasm, previously thought to be important for ion transport, did not change with age (mean = 5.4%), although there was evidence that mitochondria either divide or change in shape up to 30 days after birth. The endothelial cell thickness decreased with age from 0.6 to 0.2 microns, probably through cell elongation during vascular growth. By combining the data on endothelial mitochondria and vascularity, it was shown that the total endothelial mitochondrial volume per unit length of capillary decreased with age, whereas per unit volume of tissue it increased.

Aging↗

Electrocorticogram and sensory evoked potentials in the young hydrocephalic H-Tx rat.

The ECoG and the sensory evoked potential in response to stimulation of the contralateral forelimb were studied in control and hydrocephalic H-Tx rats between 21 and 35 days of age by recording in several positions from the dura overlying the somatosensory cortex. All hydrocephalics showed longer periods of low amplitude, high frequency ECoG activity than the controls. For the evoked potentials the hydrocephalic rats were divided into two groups: those that gave an evoked potential in at least one electrode position and those that did not give any evoked potentials. In the hydrocephalic rats that gave an evoked response the latency of the fourth phase of the evoked potential (the N2 component) was significantly longer than in the control rats suggesting that the processing of the signal within the cortex was affected by the hydrocephalus. The absence of an evoked potential in some hydrocephalic rats suggests there may be a disruption of the thalamo-cortical pathway preventing the response from reaching the cortex.

Animals↗

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.

Aging↗

The uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus.

The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days.

Aging↗

Do brain fluid ion concentrations change in hydrocephalus? A study on potassium and calcium in rats with congenital hydrocephalus.

Potassium and calcium have been measured in cerebrospinal fluid (CSF), brain interstitial fluid (ISF) and in plasma of congenitally hydrocephalic rats (H-Tx strain) and the results compared with a previous study on control, non-hydrocephalic, rats (CFY strain). Ion-selective microelectrodes were used to determine [K+] at 1-2 and 5 days and [Ca2+] at 1-2, 5, 10 and 20 days after birth. Total [Ca] was measured in plasma and CSF samples with atomic absorption spectrometry. In addition, K+ homeostasis has been studied in CSF and ISF during plasma hyperkalaemia at 5 days after birth. Apart from a raised [Ca2+] immediately after birth, hydrocephalic rats had similar CSF and ISF potassium and calcium concentrations to those found in control rats at the same age. The degree of CSF and ISF K+ homeostasis was also similar in hydrocephalic and control rats.

Animals↗

The drainage of cerebrospinal fluid in hydrocephalic rats.

Cerebrospinal fluid plateau pressures and transverse sinus plateau pressures were measured in response to a series of constant-rate infusions into the CSF in 10-day-old control and hydrocephalic H-Tx rats. In control rats the venous pressure increased with CSF pressure but to a lesser extent and around 60% of the total resistance to absorption was due to the concurrent rise in venous pressure with a hydrostatic gradient maintained between CSF and venous blood. In hydrocephalic rats the same infusion rates resulted in an increase in venous pressure which was the same magnitude as the rise in CSF pressure, resulting in zero hydrostatic gradient from CSF to blood. This suggests that CSF drainage does not take place by this route in hydrocephalic rats and that alternative drainage routes must be operating.

Animals↗

The effect of cerebrospinal fluid pressure on dural venous pressure in young rats.

In order to study cerebrospinal fluid (CSF) absorption across the dural sinus wall, the effect of CSF pressure (recorded from the cisterna magna) on dural venous pressure (recorded from the transverse sinus) was investigated in groups of rats at 2, 10, 20, and 31 days after birth and in adulthood. At normal resting pressures there was no positive pressure gradient between the CSF and sinus venous blood in 2-, 10-, and 20-day-old rats, but in 31-day-old and adult rats there was a positive gradient of 16 and 12 mm H2O, respectively. A series of constant-rate infusions of artificial CSF was made into the cisterna magna, and subsequent plateaus in both CSF and venous blood were recorded. The gradient of a plot of plateau pressure against infusion rate gave the overall resistance to absorption of the CSF for each age group, which was higher in 2- and 10-day-old rats than at three older ages. The effect on dural venous pressure was age-related, with the largest increase at 2 days, the smallest at 20 days, and no effect at 31 days or in adults. The pressure difference between CSF and sinus blood has been used to calculate resistance to absorption across the sinus wall. This showed that the high overall resistance to drainage in young rats can be largely accounted for by the rise in sinus pressure. It is concluded that drainage of CSF into the sinuses is greatly restricted in young animals.

Absorption↗