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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

Nanoparticles are distributed in the extracellular spaces but do not enter the capillary basement membrane. a Densely stained punctate nanoparticles are seen in the extracellular spaces (es) of the brain and within cell processes of neurons and possibly of astrocytes. b Neuropil and capillary showing nanoparticles (np) in the extracellular spaces of the neuropil and occasionally in cell processes but no nanoparticles are located in the capillary basement membrane (cvbm). Scale barsa 300 nm; b 500 nm
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Fig4: Nanoparticles are distributed in the extracellular spaces but do not enter the capillary basement membrane. a Densely stained punctate nanoparticles are seen in the extracellular spaces (es) of the brain and within cell processes of neurons and possibly of astrocytes. b Neuropil and capillary showing nanoparticles (np) in the extracellular spaces of the neuropil and occasionally in cell processes but no nanoparticles are located in the capillary basement membrane (cvbm). Scale barsa 300 nm; b 500 nm

Mentions: To test the capacity of the pericapillary route for lymphatic drainage, 15 nm gold nanoparticles were injected into the grey matter of the hippocampus and specimens were examined 5 min after injection. In this way the results could be compared with the injections of biotinylated Aβ. Gold nanoparticles were distributed through the extracellular spaces of the hippocampal parenchyma and some were taken up by neuronal and possibly by astrocyte processes (Fig. 4a). However, no nanoparticles were identified within capillary basement membranes (Fig. 4b) although they were in the pericapillary extracellular spaces and within adjacent neuronal processes. These results suggest that although 15 nm nanoparticles are widely distributed through the extracellular spaces they do not enter basement membranes of the perivascular lymphatic drainage pathway.Fig. 4


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)

Nanoparticles are distributed in the extracellular spaces but do not enter the capillary basement membrane. a Densely stained punctate nanoparticles are seen in the extracellular spaces (es) of the brain and within cell processes of neurons and possibly of astrocytes. b Neuropil and capillary showing nanoparticles (np) in the extracellular spaces of the neuropil and occasionally in cell processes but no nanoparticles are located in the capillary basement membrane (cvbm). Scale barsa 300 nm; b 500 nm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Nanoparticles are distributed in the extracellular spaces but do not enter the capillary basement membrane. a Densely stained punctate nanoparticles are seen in the extracellular spaces (es) of the brain and within cell processes of neurons and possibly of astrocytes. b Neuropil and capillary showing nanoparticles (np) in the extracellular spaces of the neuropil and occasionally in cell processes but no nanoparticles are located in the capillary basement membrane (cvbm). Scale barsa 300 nm; b 500 nm
Mentions: To test the capacity of the pericapillary route for lymphatic drainage, 15 nm gold nanoparticles were injected into the grey matter of the hippocampus and specimens were examined 5 min after injection. In this way the results could be compared with the injections of biotinylated Aβ. Gold nanoparticles were distributed through the extracellular spaces of the hippocampal parenchyma and some were taken up by neuronal and possibly by astrocyte processes (Fig. 4a). However, no nanoparticles were identified within capillary basement membranes (Fig. 4b) although they were in the pericapillary extracellular spaces and within adjacent neuronal processes. These results suggest that although 15 nm nanoparticles are widely distributed through the extracellular spaces they do not enter basement membranes of the perivascular lymphatic drainage pathway.Fig. 4

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