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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

Biotinylated Aβ identified in the extracellular space of hippocampal grey matter and in a capillary basement membrane. a Hippocampal neuropil showing darkly stained biotinylated Aβ in the extracellular spaces (arrows labelled Aβ); b capillary in the hippocampus showing darkly stained biotinylated Aβ in the basement membrane; c high-magnification view of the area within the square in Fig. 2b showing darkly stained biotinylated Aβ in the extracellular space (right) and throughout the capillary basement membrane (left) that encapsulates a pericyte (p); d capillary from a control hippocampus, into which no biotinylated Aβ has been injected. The basement membrane (cvbm) is negative for Aβ staining. en endothelium, lu lumen, p pericyte, cvbm cerebrovascular basement membrane. Scale barsa 500 nm; b–d 200 nm
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Fig2: Biotinylated Aβ identified in the extracellular space of hippocampal grey matter and in a capillary basement membrane. a Hippocampal neuropil showing darkly stained biotinylated Aβ in the extracellular spaces (arrows labelled Aβ); b capillary in the hippocampus showing darkly stained biotinylated Aβ in the basement membrane; c high-magnification view of the area within the square in Fig. 2b showing darkly stained biotinylated Aβ in the extracellular space (right) and throughout the capillary basement membrane (left) that encapsulates a pericyte (p); d capillary from a control hippocampus, into which no biotinylated Aβ has been injected. The basement membrane (cvbm) is negative for Aβ staining. en endothelium, lu lumen, p pericyte, cvbm cerebrovascular basement membrane. Scale barsa 500 nm; b–d 200 nm

Mentions: At 5 min after injection into the hippocampus, densely staining biotinylated Aβ is seen in the narrow extracellular spaces between neuronal and glial processes (Fig. 2a). Examination of capillary walls at the same time interval reveals the presence of dark granular staining for biotinylated Aβ within the capillary basement membrane (Fig. 2b). At higher magnification (Fig. 2c), staining for Aβ extends throughout the width of the basement membrane and on either side of a pericapillary pericyte. Images were compared with basement membranes from capillaries of animals that had received injections of phosphate buffered saline and no injection of biotinylated Aβ (Fig. 2d); basement membranes in non-injected animals show no granular dense staining for Aβ.Fig. 2


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)

Biotinylated Aβ identified in the extracellular space of hippocampal grey matter and in a capillary basement membrane. a Hippocampal neuropil showing darkly stained biotinylated Aβ in the extracellular spaces (arrows labelled Aβ); b capillary in the hippocampus showing darkly stained biotinylated Aβ in the basement membrane; c high-magnification view of the area within the square in Fig. 2b showing darkly stained biotinylated Aβ in the extracellular space (right) and throughout the capillary basement membrane (left) that encapsulates a pericyte (p); d capillary from a control hippocampus, into which no biotinylated Aβ has been injected. The basement membrane (cvbm) is negative for Aβ staining. en endothelium, lu lumen, p pericyte, cvbm cerebrovascular basement membrane. Scale barsa 500 nm; b–d 200 nm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Biotinylated Aβ identified in the extracellular space of hippocampal grey matter and in a capillary basement membrane. a Hippocampal neuropil showing darkly stained biotinylated Aβ in the extracellular spaces (arrows labelled Aβ); b capillary in the hippocampus showing darkly stained biotinylated Aβ in the basement membrane; c high-magnification view of the area within the square in Fig. 2b showing darkly stained biotinylated Aβ in the extracellular space (right) and throughout the capillary basement membrane (left) that encapsulates a pericyte (p); d capillary from a control hippocampus, into which no biotinylated Aβ has been injected. The basement membrane (cvbm) is negative for Aβ staining. en endothelium, lu lumen, p pericyte, cvbm cerebrovascular basement membrane. Scale barsa 500 nm; b–d 200 nm
Mentions: At 5 min after injection into the hippocampus, densely staining biotinylated Aβ is seen in the narrow extracellular spaces between neuronal and glial processes (Fig. 2a). Examination of capillary walls at the same time interval reveals the presence of dark granular staining for biotinylated Aβ within the capillary basement membrane (Fig. 2b). At higher magnification (Fig. 2c), staining for Aβ extends throughout the width of the basement membrane and on either side of a pericapillary pericyte. Images were compared with basement membranes from capillaries of animals that had received injections of phosphate buffered saline and no injection of biotinylated Aβ (Fig. 2d); basement membranes in non-injected animals show no granular dense staining for Aβ.Fig. 2

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