Transport of Glucose and Amino Acids in the Central Nervous System

Davson, Hugh; Zloković, Berislav V.; Rakić, Ljubisav; Segal, Malcolm B.

doi:10.1007/978-1-349-11882-3_2

Cited by 8 publications

(7 citation statements)

References 102 publications

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“…Given the close anatomical association of astrocytes described in the previous section, it has long been thought that astrocytes are critical in the development and/or maintenance of BBB characteristics (Davson and Oldendorf, 1967). A number of ectopic grafting studies and in vitro experiments have supported this idea; however, recent discoveries have necessitated a broader view of the role of astrocytes at the BBB, as well as a reexamination of the roles of other parenchymal cells and the extracellular matrix.…”

Section: A Astrocytesmentioning

confidence: 95%

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

2005

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Section: A Astrocytesmentioning

confidence: 95%

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

2005

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“…Astrocytes are important in providing structural integrity to the blood vessels and maintaining BBB integrity [58] . About 99% of brain capillaries are ensheathed by the astrocytic end-feet, and this plays a central role in the development of the specialized BBB phenotype of the brain endothelium [59] . In this study, chronic fetal hypoxia and FGR were associated with a decrease in perivascular astrocyte coverage and poor end-feet contact with blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

et al. 2017

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Chronic moderate hypoxia, such as occurs in fetal growth restriction (FGR) during gestation, compromises the blood-brain barrier (BBB) and results in structural abnormalities of the cerebral vasculature. We have previously determined the neuroprotective and antioxidant effects of maternal administration of melatonin (MLT) on growth-restricted newborn lambs. The potential of maternal MLT therapy for the treatment of cerebrovascular dysfunction-associated developmental hypoxia has also been demonstrated in newborn lambs. We assessed whether MLT had an effect on the previously reported structural and cerebral vascular abnormalities in chronically hypoxic FGR lambs. Single umbilical-artery ligation surgery was performed in fetuses at approximately 105 days of gestation (term: 147 days) to induce placental insufficiency and FGR, and treatment with either saline or an MLT infusion (0.1 mg/kg) was started 4 h after surgery. Ewes delivered naturally at term and lambs were euthanased 24 h later. We found a significant reduction in the number of laminin-positive blood vessels within the subcortical and periventricular white matter (SCWM and PVWM) and the subventricular zone (SVZ) in FGR (p < 0.0005) and FGR + MLT brains (p < 0.0005 vs. controls), with no difference found between FGR and FGR + MLT animals. This was associated with a significant decrease in VEGF immunoreactivity in FGR and FGR + MLT brains versus controls (p < 0.0005; SCWM and PVWM) and in the SVZ in FGR brains versus controls (p < 0.005) and also with significantly lower levels of proliferating blood vessels versus controls (p < 0.0005). Glucose transporter-1 immunoreactivity (vascular endothelium) was decreased in FGR versus control lambs (p < 0.0005) in SCWM, PVWM, and the SVZ; it was significantly increased in FGR + MLT lambs compared with FGR lambs in SCWM and PVWM (p < 0.005) and even more markedly in the SVZ (p < 0.0005). FGR brains showed a 72% reduction in pericyte coverage versus control lambs and 68% versus FGR + MLT in PVWM. In SCWM, we found a 77 and 73% reduction compared with control and FGR + MLT lambs, respectively, while in the SVZ, we observed a 68% reduction versus controls and a 70% reduction in FGR versus FGR + MLT lambs. Astrocyte end-feet coverage in the SCWM showed a significant 24% reduction in FGR versus control levels, a 42% decrease within the PVWM, and a 35% decrease within the SVZ versus controls. MLT normalized astrocyte attachment to blood vessels, with no difference seen between controls and FGR + MLT animals in any of the brain regions examined. We also observed a decrease in albumin extravasation and microhemorrhage in controls and FGR + MLT brains versus FGR lambs. Our results demonstrate that umbilicoplacental insufficiency is associated with FGR-produced vascular changes in the white matter and SVZ of FGR newborn brains and that maternal MLT prevented disruption of the BBB by protecting perivascular cells essential for the maintenance of vascular homeostasis and stability.

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“…Gap junctions between pial and ependymal cells establish direct continuity between ISF and CSF [29]. Flow between these compartments is a dynamic equilibrium, influenced by hydrostatic, oncotic and osmotic pressures [51]. Transport of solutes in CSF, relies upon size-independent bulk flow and size-dependent diffusion down concentration gradients.…”

Section: Bulk Flow Of Csfmentioning

confidence: 99%

Novel ventriculoperitoneal shunt in Alzheimer´s disease cerebrospinal fluid biomarkers

Silverberg¹,

Mayo²,

Saul³

et al. 2004

Expert Review of Neurotherapeutics

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Transport of Glucose and Amino Acids in the Central Nervous System

Cited by 8 publications

References 102 publications

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

Novel ventriculoperitoneal shunt in Alzheimer´s disease cerebrospinal fluid biomarkers

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Transport of Glucose and Amino Acids in the Central Nervous System

Cited by 8 publications

References 102 publications

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

Novel ventriculo­peritoneal shunt in Alzheimer´s disease cerebrospinal fluid biomarkers

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Product

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Novel ventriculoperitoneal shunt in Alzheimer´s disease cerebrospinal fluid biomarkers