Limits...
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

Distribution in the brain of 15 nm nanoparticles injected into the CSF. Groups of 15 nm nanoparticles are present in the pial-glial basement membrane of a cortical artery 5 min after injection into the CSF of the cisterna magna. a Low-power transmission electronmicrograph of an artery near the surface of the cerebral cortex. Note that cells and basement membranes form compact layers and there is no Virchow–Robin space. Dense nanoparticles form lines or groups in the pial-glial basement membrane between the pia mater and the glia limitans around nearly half the circumference of the artery but no nanoparticles are seen in basement membranes between smooth muscle cells. b Higher magnification of the square labelled 1 in a. Layers of the artery wall can be identified moving outwards from the lumen (lu) through the endothelium (en), smooth muscle coat (sm) and a layer of pia mater (pm) to the glia limitans of the brain parenchyma (pa). Dense groups and single nanoparticles (np) are located mainly in the pial-glial basement membrane (cvbm) between the pia mater (pm) and the adjacent glia limitans. Scale barsa 1 μm; b 500 nm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835509&req=5

Fig5: Distribution in the brain of 15 nm nanoparticles injected into the CSF. Groups of 15 nm nanoparticles are present in the pial-glial basement membrane of a cortical artery 5 min after injection into the CSF of the cisterna magna. a Low-power transmission electronmicrograph of an artery near the surface of the cerebral cortex. Note that cells and basement membranes form compact layers and there is no Virchow–Robin space. Dense nanoparticles form lines or groups in the pial-glial basement membrane between the pia mater and the glia limitans around nearly half the circumference of the artery but no nanoparticles are seen in basement membranes between smooth muscle cells. b Higher magnification of the square labelled 1 in a. Layers of the artery wall can be identified moving outwards from the lumen (lu) through the endothelium (en), smooth muscle coat (sm) and a layer of pia mater (pm) to the glia limitans of the brain parenchyma (pa). Dense groups and single nanoparticles (np) are located mainly in the pial-glial basement membrane (cvbm) between the pia mater (pm) and the adjacent glia limitans. Scale barsa 1 μm; b 500 nm

Mentions: Figure 5 shows an artery near the surface of the mouse cerebral cortex with a compact wall and no perivascular space. An area of wall in the square box in Fig. 5a is shown at higher magnification in Fig. 5b. A group of 15 nm gold nanoparticles with some single nanoparticles is present mainly in the basement membrane on the outer aspect of the artery between the layer of leptomeningeal pia mater and the astrocyte layer of glia limitans of the brain (Fig. 5b). This layer of basement membrane is shared by pia mater and glia limitans (the pial-glial basement membrane) and is distinct from the layers of basement membrane surrounding smooth muscle cells in the tunica media that act as the pathway for drainage of fluid and solutes out of the brain. Figure 5a, b also shows that there is no space between layers of the artery wall and the glia limitans.Fig. 5


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)

Distribution in the brain of 15 nm nanoparticles injected into the CSF. Groups of 15 nm nanoparticles are present in the pial-glial basement membrane of a cortical artery 5 min after injection into the CSF of the cisterna magna. a Low-power transmission electronmicrograph of an artery near the surface of the cerebral cortex. Note that cells and basement membranes form compact layers and there is no Virchow–Robin space. Dense nanoparticles form lines or groups in the pial-glial basement membrane between the pia mater and the glia limitans around nearly half the circumference of the artery but no nanoparticles are seen in basement membranes between smooth muscle cells. b Higher magnification of the square labelled 1 in a. Layers of the artery wall can be identified moving outwards from the lumen (lu) through the endothelium (en), smooth muscle coat (sm) and a layer of pia mater (pm) to the glia limitans of the brain parenchyma (pa). Dense groups and single nanoparticles (np) are located mainly in the pial-glial basement membrane (cvbm) between the pia mater (pm) and the adjacent glia limitans. Scale barsa 1 μm; b 500 nm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Distribution in the brain of 15 nm nanoparticles injected into the CSF. Groups of 15 nm nanoparticles are present in the pial-glial basement membrane of a cortical artery 5 min after injection into the CSF of the cisterna magna. a Low-power transmission electronmicrograph of an artery near the surface of the cerebral cortex. Note that cells and basement membranes form compact layers and there is no Virchow–Robin space. Dense nanoparticles form lines or groups in the pial-glial basement membrane between the pia mater and the glia limitans around nearly half the circumference of the artery but no nanoparticles are seen in basement membranes between smooth muscle cells. b Higher magnification of the square labelled 1 in a. Layers of the artery wall can be identified moving outwards from the lumen (lu) through the endothelium (en), smooth muscle coat (sm) and a layer of pia mater (pm) to the glia limitans of the brain parenchyma (pa). Dense groups and single nanoparticles (np) are located mainly in the pial-glial basement membrane (cvbm) between the pia mater (pm) and the adjacent glia limitans. Scale barsa 1 μm; b 500 nm
Mentions: Figure 5 shows an artery near the surface of the mouse cerebral cortex with a compact wall and no perivascular space. An area of wall in the square box in Fig. 5a is shown at higher magnification in Fig. 5b. A group of 15 nm gold nanoparticles with some single nanoparticles is present mainly in the basement membrane on the outer aspect of the artery between the layer of leptomeningeal pia mater and the astrocyte layer of glia limitans of the brain (Fig. 5b). This layer of basement membrane is shared by pia mater and glia limitans (the pial-glial basement membrane) and is distinct from the layers of basement membrane surrounding smooth muscle cells in the tunica media that act as the pathway for drainage of fluid and solutes out of the brain. Figure 5a, b also shows that there is no space between layers of the artery wall and the glia limitans.Fig. 5

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