The development of ion regulation at the blood-brain barrier.
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Aging↗
Biomedical subjects
R F Keep
Publications and source records attributed to R F Keep.
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↗
Decrease in perfusion of cerebral capillaries during incomplete ischemia and reperfusion.
The effect of unilateral, incomplete cerebral ischemia on CBF, unidirectional flux of alpha-aminoisobutyric acid (AIB) and sodium, and number of perfused capillaries during ischemia and reperfusion was measured in the cortex of gerbils with symptomatic ischemia. Three hours of unilateral carotid occlusion reduced the CBF to the ipsilateral cortex by 81%, with a smaller 30% decrease in the contralateral cortex. Following 11 min of reperfusion, CBF in the ipsilateral cortex returned to the preischemic value, while the contralateral blood flow decreased to 50% of control. The transfer constants for AIB and sodium in the ipsilateral cortex were reduced by 67 and 53%, respectively, after 3 h of ischemia, with no change in the contralateral cortex. The transfer constant for AIB remained decreased by 48% during the first 20 min of reperfusion, while that for sodium returned to its control value. The number of perfused capillaries was reduced 54% by 3 h of ischemia and remained decreased by 20% after 11 min of reperfusion. These data indicate that 3 h of unilateral carotid occlusion reduces the number of perfused capillaries in the ipsilateral cortex during the ischemic period. Further, the early reperfusion phase is characterized by a mismatch between capillary perfusion and CBF. Finally, early in the postischemic phase, sodium transport undergoes a selective stimulation, probably as a result of stimulation of ion transport.
Aminoisobutyric Acids↗
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 development of ion regulation in mammalian brain extracellular fluid.
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Animals↗
Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat.
1. In vivo measurements of plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) ionic Ca2+ concentrations ([Ca2+]) have been made in anaesthetized rats aged between 19 days gestation and adult using calcium-selective microelectrodes. Total calcium concentration ([ Ca]) has also been determined in plasma and CSF samples by atomic absorption spectrometry. 2. Under control conditions, plasma, CSF and ISF [Ca2+] showed a small, but significant, decrease with age. Plasma and CSF, but not ISF, showed a transient hypocalcaemia at birth. After birth there were no significant differences between plasma, CSF and ISF [Ca2+], except in adult rats where CSF [Ca2+] was significantly lower than plasma [Ca2+]. The age-related changes in CSF and ISF [Ca2+] were small and it is uncertain as to whether they may have any functional significance. 3. Under control conditions, plasma and CSF [Ca] also declined with age. The fall in plasma [Ca] paralleled the changes in plasma [Ca2+]. The decrease in CSF [Ca] was steeper than that in [Ca2+] and indicated a higher proportion of protein-bound or complexed calcium in the CSF of young when compared to old rats. 4. Acute plasma hypercalcaemia was induced by intramuscular injections of calcium gluconate and consequent changes in CSF or ISF [Ca2+] were monitored in vivo. There was very weak regulation of CSF and ISF [Ca2+] at 21 days gestation, which may reflect placental control over fetal plasma calcium. Soon after birth there was good regulation in both ISF and CSF [Ca2+]. CSF [Ca] was also measured during hypercalcaemia in samples from post-natal rats and there was similar regulation to that in CSF [Ca2+]. 5. It is concluded that under control conditions, during rat development, CSF and ISF [Ca2+] closely follow changes in plasma [Ca2+], but that soon after birth homeostatic mechanisms develop to prevent large fluctuations in brain fluid calcium.
Aging↗
Brain interstitial fluid calcium concentration during development in the rat: control levels and changes in acute plasma hypercalcaemia.
Age-related changes in brain interstitial fluid (ISF) ionic calcium, in ionic and total calcium in plasma and the effect of plasma hypercalcaemia on ISF calcium have been studied in rats aged between late gestation and adult. ISF ionic [Ca2+] decreased significantly with development from 1.6 mM to 1.2 mM. Plasma ionic [Ca2+] was not significantly different from ISF [Ca2+] apart from a transient hypocalcaemia at birth which was not reflected in the ISF. Plasma total calcium was around 2X ionic [Ca2+] and showed the same age-related decrease. In acute plasma hypercalcaemia induced by calcium gluconate injections, there was only weak regulation of ISF Ca2+ at 21 days gestation but a rapid improvement after birth resulted in excellent control by 5 days.
Aging↗
Choroid plexus structure and function in young rats on a high-potassium diet.
Rats, 20 days old, were fed a diet containing 20% KCl for 10 days. At 30 days these rats had lower body, brain and choroid plexus weights than matched controls and plasma [K+] was increased to 7.5 mM compared to 4.1 mM for controls. Cerebrospinal fluid (CSF) [K+] and bulk fluid secretion were not changed by the high K+ diet but there was a mild metabolic acidosis. The fourth ventricle choroid plexus was prepared for transmission electron microscopy and the structure of the epithelium analysed by quantitative stereology. The high K+ rats had a large increase in the mitochondrial volume fraction of the epithelium due to a 36% increase in individual mitochondrial volume. The high-K+ rats also had a decrease in the apical surface density of the epithelium due to a 41% decrease in the height of the microvilli. It is concluded that the increase in mitochondrial volume may provide the additional energy required for the increased transport of K+ out of the CSF in hyperkalaemia. The reduction in height of the microvilli could be a means for maintaining a normal CSF bulk secretion rate despite the increase in K+ transport required to maintain normal CSF [K+] in hyperkalaemia.
Animals↗
The control of potassium concentration in the cerebrospinal fluid and brain interstitial fluid of developing rats.
1. In situ measurements of plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) K+ concentrations have been made in anaesthetized rats aged between 19 days gestation and 30 days after birth using K+-selective micro-electrodes. 2. Under control conditions, plasma, CSF and ISF [K+] did not vary significantly with age, the over-all mean concentrations being 3.8, 3.1 and 3.2 mM respectively. The CSF and ISF [K+] were significantly lower than plasma [K+] at all ages. 3. It is concluded that young rats, from the age of 19 days gestation, can normally maintain plasma-to-CSF and plasma-to-ISF gradients similar to those in the adult, presumably by action of the blood-CSF and blood-brain barriers. 4. During acute plasma hyperkalaemia there was very little regulation of CSF [K+] at 21 days gestation, but after birth there was a gradual improvement in CSF K+ homeostasis until by 30 days after birth a normal CSF [K+] could be maintained. 4. There was no regulation of ISF [K+] during hyperkalaemia at 21 days gestation, although after birth there was a rapid improvement in ISF K+ homeostasis. 1-day-old neonates were able to maintain a normal forebrain ISF [K+] during hyperkalaemia. 6. It is concluded that the onset of both CSF and ISF K+ homeostasis takes place at around birth in rats. However, K+ homeostasis matures more rapidly in the ISF than in the CSF. This suggests that, at least in the neonatal period, the CSF is not essential for ISF [K+] regulation.
Animals↗
Effect of chronic maternal hyperkalaemia on plasma, cerebrospinal fluid and brain interstitial fluid potassium in developing rats.
Plasma hyperkalaemia was induced in pregnant and lactating rats using a high potassium diet. Fetuses of high-K-diet mothers showed no increase in the potassium concentration [( K+]) of plasma, cerebrospinal fluid (CSF) and brain interstitial fluid, presumably due to placental control. Neonates from high-K-diet rats did show an increase in plasma [K+] but this increase was very small and there was no increase in CSF or interstitial fluid [K+]. Maternal milk [K+] was not affected by plasma hyperkalaemia. Weanling rats fed the high-K diet directly showed marked plasma hyperkalaemia but no increase in CSF or interstitial fluid [K+]. Thus, prior to weaning, a relatively stable plasma [K+] is maintained by maternal influence reducing the need for direct brain fluid K+ regulation.
Animals↗
A morphometric analysis of the development of the fourth ventricle choroid plexus in the rat.
The choroid plexus from the rat fourth ventricle was investigated at ages from 16 days of gestation to 30 days after birth. Choroid plexus weights were measured and light and electron micrographs were analysed by quantitative stereological techniques at 4 levels of magnification. There was a 10-fold increase in plexus weight between 19 days of gestation and 30 days after birth which was largely due to an increase in epithelial weight, with little change occurring in the connective tissue core. Before birth, epithelial cell height decreased whereas between 10 and 30 days after birth cross-sectional area increased, both events being accompanied by corresponding changes in cell volume. Large intracellular stores of glycogen were present around birth, when they occupied up to 20% of the cell volume. After birth there were significant increases in apical microvillus height, the number of microvilli per cell and in the size of the mitochondria, suggesting that a large increase in choroid plexus secretory function, or the commencement of a new function, occurs after birth in the rat.
Animals↗