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Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

Morris AW, Sharp MM, Albargothy NJ, Fernandes R, Hawkes CA, Verma A, Weller RO, Carare RO - Acta Neuropathol. (2016)

Bottom Line: Nanoparticles did not enter capillary basement membranes from the extracellular spaces.The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved.The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Southampton, Southampton General Hospital, MP806, Tremona Road, Southampton, Hampshire, SO16 6YD, UK.

ABSTRACT
In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

No MeSH data available.


Related in: MedlinePlus

Extracellular space in grey matter of the hippocampus and its connection to capillary basement membrane. a Grey matter with the extracellular space outlined in yellow. There is a capillary in the bottom left-hand corner. Capillary lumen (lu). b High-magnification view of the junction of the extracellular space (es) with the capillary basement membrane (cvbm) at the level of the astrocyte membrane. Endothelial cell of the capillary (en); astrocyte of the glia limitans (a). Scale barsa 500 nm; b 250 nm
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Fig1: Extracellular space in grey matter of the hippocampus and its connection to capillary basement membrane. a Grey matter with the extracellular space outlined in yellow. There is a capillary in the bottom left-hand corner. Capillary lumen (lu). b High-magnification view of the junction of the extracellular space (es) with the capillary basement membrane (cvbm) at the level of the astrocyte membrane. Endothelial cell of the capillary (en); astrocyte of the glia limitans (a). Scale barsa 500 nm; b 250 nm

Mentions: Electron microscope preparations were used to examine the relationship between the extracellular spaces in the mouse hippocampus and basement membranes surrounding capillaries. Figure 1a shows the narrow and tortuous extracellular spaces in the brain parenchyma outlined in yellow and how they abut on to the walls of capillaries. At higher magnification in Fig. 1b, the interface of the extracellular space between astrocyte processes and the basement membrane of the capillary wall can be demonstrated. The basement membrane around capillaries is formed from two elements derived on one side from the astrocytes of the glia limitans and on the other side from capillary endothelium; it is in direct focal contact with the extracellular space of the brain.Fig. 1


Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

Morris AW, Sharp MM, Albargothy NJ, Fernandes R, Hawkes CA, Verma A, Weller RO, Carare RO - Acta Neuropathol. (2016)

Extracellular space in grey matter of the hippocampus and its connection to capillary basement membrane. a Grey matter with the extracellular space outlined in yellow. There is a capillary in the bottom left-hand corner. Capillary lumen (lu). b High-magnification view of the junction of the extracellular space (es) with the capillary basement membrane (cvbm) at the level of the astrocyte membrane. Endothelial cell of the capillary (en); astrocyte of the glia limitans (a). Scale barsa 500 nm; b 250 nm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835509&req=5

Fig1: Extracellular space in grey matter of the hippocampus and its connection to capillary basement membrane. a Grey matter with the extracellular space outlined in yellow. There is a capillary in the bottom left-hand corner. Capillary lumen (lu). b High-magnification view of the junction of the extracellular space (es) with the capillary basement membrane (cvbm) at the level of the astrocyte membrane. Endothelial cell of the capillary (en); astrocyte of the glia limitans (a). Scale barsa 500 nm; b 250 nm
Mentions: Electron microscope preparations were used to examine the relationship between the extracellular spaces in the mouse hippocampus and basement membranes surrounding capillaries. Figure 1a shows the narrow and tortuous extracellular spaces in the brain parenchyma outlined in yellow and how they abut on to the walls of capillaries. At higher magnification in Fig. 1b, the interface of the extracellular space between astrocyte processes and the basement membrane of the capillary wall can be demonstrated. The basement membrane around capillaries is formed from two elements derived on one side from the astrocytes of the glia limitans and on the other side from capillary endothelium; it is in direct focal contact with the extracellular space of the brain.Fig. 1

Bottom Line: Nanoparticles did not enter capillary basement membranes from the extracellular spaces.The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved.The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, University of Southampton, Southampton General Hospital, MP806, Tremona Road, Southampton, Hampshire, SO16 6YD, UK.

ABSTRACT
In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

No MeSH data available.


Related in: MedlinePlus