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H C Jones

Publications and source records attributed to H C Jones.

At least 37 records · Page 2Linked to original sources
PubMed1998

The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis.

Although gliosis has been reported to be a common and persistent feature in the white matter of hydrocephalic brains, no studies have identified the cell types that characterize this response. Therefore, the present study has employed histochemical methods to evaluate microglial cells in the brains of infant rats with inherited hydrocephalus. This strain of rats acquires hydrocephalus during late fetal stages due to aqueductal stenosis. Tissue from the sensorimotor and auditory cortices of 12- and 21-day-old hydrocephalic and normal H-Tx rats was processed and stained for the lectin microglial marker Griffonia simplicifolia (GSA-IB4). During the progression of hydrocephalus, GSA-positive cells exhibited three changes: (1) Cytologically, the cell bodies were enlarged, and their processes were thicker, longer and more numerous. These changes were most notable in the gray matter. (2) The packing density of GSA-positive cells was either increased or decreased, depending on the age of the animal and the severity of hydrocephalus. (3) Localized clusters of GSA-positive cells were conspicuous in the white matter of 12-day animals with mild hydrocephalus, and in the gray matter of 21-day animals with severe hydrocephalus. These results indicate that the microglial response is initiated during intermediate stages of hydrocephalus, and is not restricted to the periventricular white matter. These changes may signal other pathophysiologic events in the hydrocephalic brain, and demonstrate that microglia constitute one important element in the gliosis that accompanies hydrocephalus.

Animals↗
PubMed1997

Ultrastructural changes in the deep cortical pyramidal cells of infant rats with inherited hydrocephalus and the effect of shunt treatment.

Pathological changes in the cortical gray matter in infantile hydrocephalus vary with the age at onset and may not be reversible with shunt treatment. We have used electron microscopy to investigate the sequence of pathological change and the effect of shunt treatment on layer VI pyramidal cells from infant H-Tx rats with inherited early-onset hydrocephalus. Tissue was prepared from the frontal and visual cortex of control and hydrocephalic rats at 4, 11, and 21 days after birth, together with 21-day rats previously treated with ventriculosubcutaneous shunts at 4-5 or 10-11 days after birth. Both cortical regions gave similar results but the effects were more severe in the visual cortex. In the early stages of hydrocephalus, the pyramidal cells were in clusters with fewer mature dendrites and less cytoplasmic organization than those in control rats, and some neuronal processes were vacuolated. In intermediate hydrocephalus the changes were more severe, with vacuolated cytoplasm, fewer cytoplasmic organelles, frequent swollen processes, and infrequent synapses. In advanced hydrocephalus at 21 days, many neurons showed degenerative changes, with edematous Golgi and dilated endoplasmic reticulum, distorted mitochondria, and single ribosomes. The neuropil contained many spongy areas with distended profiles. Shunt treatment prevented most of the changes if carried out at 4 days. Shunt treatment at 11 days also gave a dramatic recovery at the cellular level, but there were more immature pyramidal cells and edematous processes in the neuropil than in the 4-day-treated rats. The changes in hydrocephalus are consistent with progressive neuronal damage, which is largely prevented by early shunt treatment.

Animals↗
PubMed1997

An abnormal distribution of melatonin receptors in the newborn rat with inherited prenatal hydrocephalus.

Melatonin binding in the brain of hydrocephalic H-Tx rats was examined by autoradiography. At the time of birth, hydrocephalic animals showed an abnormality in the distribution of high-affinity melatonin receptors dorsal to the cerebral aqueduct when compared to controls. Whereas newborn rats of the H-Tx strain that were unaffected by hydrocephalus had melatonin receptors in a tectal midsagittal strip overlying the aqueduct and spanning the anterior half of the tectum, hydrocephalic rats lacked melatonin receptors in the most anterior part of this region. In these animals, the length of the aqueduct over which receptors were missing was compressed and was additionally occluded by dystrophic ependyma. The first signs of ventricular expansion characteristic of hydrocephalus were evident.

Animals↗
PubMed1997

Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy.

The pathophysiology of infantile hydrocephalus is poorly understood, and shunt treatment does not always lead to a normal neurological outcome. To investigate some of the neurochemical changes in infantile hydrocephalus and the response to shunt treatment, we have used high-resolution 1H-NMR spectroscopy to analyze extracts of cerebral cortex from H-Tx rats, which have inherited hydrocephalus with an onset in late gestation. Hydrocephalic rats and rats with shunts placed at either 4 or 12 days after birth were studied at 21 days after birth, together with age-matched control littermates. In hydrocephalic rats there was a 46-62% reduction in the following compounds: myo-inositol, creatine, choline-containing compounds, N-acetyl aspartate, taurine, glutamine, glutamate, aspartate, and alanine. Phosphocreatine, glycine, GABA, and lactate were also reduced but not significantly. These changes are consistent with neuronal atrophy rather than ischemic damage. In hydrocephalic rats that received shunt treatment at 4 days, there were no significant reductions in any chemicals, indicating a normal complement of neurons. However, some compounds, particularly taurine, were elevated above control. After treatment at 12 days, N-acetyl aspartate and aspartate remained significantly reduced, suggesting continued neuronal deficiency.

Animals↗
PubMed1997

Progressive changes in cortical metabolites at three stages of infantile hydrocephalus studied by in vitro NMR spectroscopy.

Infantile hydrocephalus is most often caused by an obstruction in the cerebrospinal fluid flow pathway and results in ventricular dilatation and chronic trauma to the surrounding brain. Surgical treatment alleviates the condition but does not cure or prevent neurological deficits. The H-Tx rat has severe hydrocephalus due to a spontaneous aqueduct obstruction in late gestation. In order to determine how hydrocephalus affects brain metabolism in tissue adjacent to the expanded ventricles, cortical extracts have been made from groups of hydrocephalic and control littermates with early, intermediate, and advanced hydrocephalus at 4, 11, and 21 days after birth. Extracts were analyzed with 1H and 31P NMR spectroscopy and metabolite peaks were quantified using an external standard. Metabolite concentrations were calculated relative to tissue wet weight and subsequently expressed relative to tissue dry weight, using values for water content obtained from additional groups of rats. In early hydrocephalus there was a significant decrease in the phosphomonoester phosphorylcholine, and there were small, nonsignificant changes in other compounds. By 11 days, in addition to phosphomonoesters, there were significant decreases in ATP, phosphocreatine, and in inorganic phosphate, but with no change in lactate. By 21 days there were also substantial decreases in cholines, inositol, creatine, glutamate, glutamine, aspartate, N-acetylaspartate, alanine, and taurine. It is concluded that the sequence of pathological events starts with changes in membrane lipids. This is followed by reductions in energy metabolite which leads to cell swelling with loss of intracellular osmolytes and neurotransmitters. These changes are discussed in relation to hydrocephalus pathophysiology and to prevention and reversibility with shunt treatment.

Age Factors↗
PubMed1996

The effect of inherited hydrocephalus and shunt treatment on cortical pyramidal cell dendrites in the infant H-Tx rat.

The neuronal basis for neurological deficits in infantile hydrocephalus is poorly understood. Changes in the dendritic architecture of pyramidal cells of the auditory cortex have been measured at 21 days after birth in H-Tx rats. Tissue was prepared by the rapid Golgi method from hydrocephalic and control litter-mates, together with hydrocephalic rats with ventriculo-subcutaneous shunts placed at 3-4 days or at 10 days after birth. Layer V pyramidal cells were analyzed quantitatively on a light microscope at a magnification of 250 or 400 x. When compared to control, the hydrocephalic rats had a 30% reduction in the cortical thickness whereas in the shunt-treated rats it was similar to control. For both the apical and the basal dendrites, the distance extended from the soma was reduced in hydrocephalic rats by 49-57%, and the total length of the dendritic trees was decreased by 61 and 77%, respectively. Rats shunt-treated at 3-4 days had small dendrite changes which, in most cases, were not significantly different from control. Rats shunt-treated at 10 days had dendrites which were indistinguishable from untreated hydrocephalic rats. Dendritic branch patterns were also affected; the number and mean length of branch segments were reduced in both the hydrocephalic and the 10-day shunt group, with only small changes in the earlier group. Overall, the basal dendrites were more severely affected than the apical dendrites. It is concluded that infantile hydrocephalus results in severe neuronal abnormalities which can largely, but not completely, be prevented by shunt treatment performed in the early stages.

Analysis of Variance↗
PubMed1996

Metabolite changes in the cerebral cortex of treated and untreated infant hydrocephalic rats studied using in vitro 31P-NMR spectroscopy.

The effect of hydrocephalus on cerebral energy metabolites and on intermediates of membrane phospholipid metabolism has been studied in H-Tx rats with inherited infantile hydrocephalus. Hydrocephalic rats and rats with shunts placed at 4-5 days or at 10 days after birth were subjected to magnetic resonance imaging in vivo before 21 days of age to determine the dimensions of the ventricles and cortex. At 21 days, the brains from the three groups of rats, together with age-matched control littermates, were frozen in situ, and chloroform/methanol extracts of cerebral cortex were prepared for high-resolution 31P-NMR spectroscopy. Hydrocephalus resulted in modest decreases in most metabolites quantified. Levels of phosphocreatine, ATP, and diphosphodiesters plus NAD were significantly reduced by 23-32%, and inorganic phosphate content was reduced but not significantly. Levels of the membrane phospholipid intermediates phosphorylethanolamine, glycerophosphorylethanolamine, and glycerophosphorylcholine were also significantly reduced by 30-33%, indicating changes in membrane metabolism. These general decreases are consistent with a loss of cell contents, possibly due to changes in dendrite structure in hydrocephalus. Rats shunt-treated at 4-5 days were similar to control rats for all energy metabolites, but those treated later at 10 days had reduced phosphocreatine and ATP levels. Shunt-treated rats also had reductions in levels of membrane phospholipids, some of which occurred in sham-operated rats. It is concluded that hydrocephalus leads to reductions in levels of energy metabolites and in levels of membrane phospholipids and that the changes in energy metabolites can be reversed by early, but not by later, shunt treatment.

Adenosine Triphosphate↗
PubMed1995

Shunt treatment at two postnatal ages in hydrocephalic H-Tx rats quantified using MR imaging.

The H-Tx rat has inherited hydrocephalus with an onset in late gestation. Ventriculosubcutaneous shunts were placed in a group of hydrocephalic pups at 3-6 days after birth and in another group at 8-12 days after birth. Multislice proton magnetic resonance (MR) images were taken of shunt-treated pups at 7, 14, or 21 days and of age-matched control and untreated hydrocephalic rats and were subjected to quantitative analysis. Some rats were also imaged before surgery. The volume of the ventricles of untreated hydrocephalic pups increased linearly with age at a rate of 52 microliters/day. The ventricles of shunted pups were reduced from the preshunt condition and were around 20% of age-matched hydrocephalic rats. There was no significant difference in the post-shunt volume between early and late shunt groups. The cortical mantle thickness in both groups of shunt-treated rats was significantly thicker than in untreated pups and close to that of control rats. It is concluded that shunt treatment at both ages reversed the hydrocephalus as measured from MR images, although other evidence from fixed brains suggests that normal morphology may not be achieved at the cellular level even for early shunts.

Aging↗
PubMed1995

Learning deficits in congenitally hydrocephalic rats and prevention by early shunt treatment.

Shunt surgery is the usual treatment for infantile hydrocephalus; however, the extent to which it avoids subsequent neurological deficits is uncertain. The effect of early-onset hydrocephalus was tested in H-Tx rats using the Morris water maze. Spatial learning was assessed at 21 days after birth in control (n = 18), hydrocephalic (n = 18) and hydrocephalic rats shunt-treated at 4-5 (n = 7) or at 10-12 days of life (n = 13). The time taken to find a hidden platform was measured in five trials on 2 consecutive days and the data analyzed by one- and two-way ANOVA and t-tests. The latencies of the control rats decreased significantly between the first and second trial on the 1st day, and learning was retained until the 2nd day. The hydrocephalic group had longer latencies than controls on both days, with no significant decrease between any trials. Performance was not significantly different between the two shunt groups. Overall, the shunted rats had latencies which were not significantly different from controls but were significantly lower than hydrocephalics. Despite this, the shunted rats did not perform as well as the controls. It is concluded that, although shunt treatment improved learning, some effects of early-onset hydrocephalus may not be reversible and/or a longer recovery time is required.

Animals↗
PubMed1995

Uncoupling of LCBF and LCGU in two different models of hydrocephalus: a review.

We have used two different experimental models to examine the relationship between local cerebral blood flow and metabolism in hydrocephalus. In our first experiments local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured by quantitative autoradiographic methods in adult rats rendered hydrocephalic, though asymptomatic, by the injection of kaolin intracisternally at 3 weeks of age and in control animals. There were no significant differences in LCGU or LCBF in any of the 29 areas of grey matter examined, including layer IV of the cerebral cortex. Scanning across the cerebral cortex revealed an appreciable fall in LCGU and LCBF towards the inside and the outside of the mantle in control animals. Hydrocephalus had no significant effect on this "transmantle" pattern of reduction in cortical metabolism towards the periphery, but in contrast, significantly enhanced the reduction in cortical blood flow in 7 out of the 10 cortical regions examined. Hence, in this model of asymptomatic hydrocephalus there is relative uncoupling of LCBF and LCGU in the inner and outer layers of the cerebral mantle. In a study performed in congenitally hydrocephalic H-Tx rats at 10, 20 and 28 days we found that uptake of deoxyglucose was impaired in hydrocephalic rats compared with their non-hydrocephalic siblings. Small changes were seen at 10 and 21 days, but statistically significant changes were seen only at 28 days. A small reduction in LCBF was observed in all regions at 10 days, with statistically significant differences between control and hydrocephalic rats in auditory and parietal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Transendothelial electrical potential across pial vessels in anaesthetised rats: a study of ion permeability and transport at the blood-brain barrier.

Brain pial microvessels have previously been demonstrated to have blood-brain barrier properties. The potential difference (PD) across exposed brain pial microvessels, 20-60 microns in diameter and superfused with artificial CSF, has been measured in anaesthetised rats using glass microelectrodes. The PD on insertion into venous vessels, V(in), was 3.2 mV lumen negative, and in arterial vessels it was higher at 4.5 mV. Superfusion with high K(+)-CSF, made by replacing Na+ with K+, caused a positive deflection in PD, VK+, whereas reducing the Na+ alone, by replacing Na+ by Tris-HCl, made the lumen more negative. These two effects were additive. Studies on venous vessels showed that ouabain had no effect on V(in) and only affected VK+ under conditions of low Na pre-exposure. Neither histamine nor cimetidine had any effect on V(in) or VK+ whereas tetraethylammonium, a K(+)-channel blocker, reduced VK+ by 20%. These experiments demonstrate that changes in PD caused by changing abluminal Na+ or K+ are due predominantly to movement of ions through channels in the endothelial cell membranes, and that actions that alter the activity of the Na+,K(+)-ATPase or reduce the resistance of the paracellular pathway in parallel with increased membrane permeability have less effect on the PD.

Anesthesia↗
PubMed1994

Ventricle shunting in young H-Tx rats with inherited congenital hydrocephalus: a quantitative histological study of cortical grey matter.

Shunt surgery is the usual treatment for infantile hydrocephalus, but its precise effects on ventricles and cortex are not well understood. Infant H-Tx rats with inherited hydrocephalus, which have progressive enlargement of the lateral ventricles and thinned cerebral cortex, have been used to study the effect of ventriculosubcutaneous shunts by quantitative light microscopy. Two groups of rats received shunts at mean ages of 7 and 13 days after birth. The brains were processed for wax histology at either 14 or 21 days (n = 3 per group) together with age-matched control and unshunted (hydrocephalic) rats. Ventricle areas were measured and the volume calculated and the cortical layers in five cortical regions were measured. Shunting prevented further expansion of ventricles which were already enlarged at the time of operation, and resulted in volumes which were intermediate between those in control and unshunted rats. Cortical thinning was partially reversed by shunting and the thickness and number of discernible cortical laminae was improved. It is concluded that shunting was largely successful at preventing the pathological effects of hydrocephalus.

Age Factors↗
PubMed1993

The transendothelial DC potential of rat blood-brain barrier vessels in situ.

The recorded potential between the abluminal CSF and the vessel lumen, 3-4 mV, blood negative is similar to that recorded in frog and can account for most or all of the previously-reported PD between CSF and blood. It is not affected by substances that alter paracellular permeability and hence is mainly generated by the properties of endothelial cell membranes. Unlike the PD recorded in frog brain vessels, the PD in rat is not sensitive to the Na(+)-K+ATPase inhibitor, ouabain, which suggests that although electrogenic Na(+)-K+ transport is known to be present, the contribution it makes to the PD is not detectable. This suggests that the changes in PD recorded when abluminal [K+] or [Na+] are altered, are a result of the passive permeability properties of the endothelial cell membranes.

Animals↗
PubMed1993

Local cerebral blood flow in rats with congenital hydrocephalus.

Local cerebral blood flow (LCBF) has been measured by [14C]iodoantipyrine quantitative autoradiography in H-Tx rats with inherited congenital hydrocephalus at 10, 21, and 30 days after birth. LCBF at 10 days was uniformly low in all ten brain regions studied and not significantly different between hydrocephalic and age-matched control rats. By 21 days LCBF had increased significantly in control rats. LCBF was significantly lower (< 69%) in the hydrocephalics in all cortical regions and in the inferior colliculus LCBF at both 21 and 30 days. The cerebellar cortex, pons, and caudate were not significantly affected. At 30 days LCBF ranged from 55 to 115 ml 100 g-1 min-1 for hydrocephalics and from 100 to 183 ml 100 g-1 min-1 for controls.

Animals↗