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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

Immunocytochemistry/confocal images showing that 5 min after the injection of soluble Aβ into the hippocampus, Aβ is associated with basement membrane proteins within the wall of an artery in the hippocampal fissure. a Aβ (red) in the wall of a leptomeningeal artery; b laminin (blue); c a layer of smooth muscle cells (green) in the artery wall that is most clearly seen when the vessel is cut in cross section; d a merged image showing co-localisation of Aβ and laminin (purple–see arrows) associated with the smooth muscle cells. The outermost layer of the artery, the tunica adventitia (ta), is stained only for laminin (blue) and not for Aβ. SP5 Leica confocal image. Scale bar 50 μm
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Fig3: Immunocytochemistry/confocal images showing that 5 min after the injection of soluble Aβ into the hippocampus, Aβ is associated with basement membrane proteins within the wall of an artery in the hippocampal fissure. a Aβ (red) in the wall of a leptomeningeal artery; b laminin (blue); c a layer of smooth muscle cells (green) in the artery wall that is most clearly seen when the vessel is cut in cross section; d a merged image showing co-localisation of Aβ and laminin (purple–see arrows) associated with the smooth muscle cells. The outermost layer of the artery, the tunica adventitia (ta), is stained only for laminin (blue) and not for Aβ. SP5 Leica confocal image. Scale bar 50 μm

Mentions: To demonstrate that soluble Aβ injected into the hippocampus reaches leptomeningeal arteries 5 min after injection, sections of brain were examined by immunocytochemistry and confocal microscopy. Figure 3 shows a series of confocal images that depict staining for Aβ, basement membrane laminin and smooth muscle actin. The leptomeningeal artery in Fig. 3 is seen as a cylinder viewed obliquely and end-on. Aβ (Fig. 3a) has a similar pattern of staining in the vessel wall to laminin (Fig. 3b) but not exactly the same. Differences can be detected in the merged image (Fig. 3d); although Aβ merges with laminin throughout the length of the section of the vessel wall, the tunica adventitia on the outer aspect of the artery stains for laminin but is devoid of Aβ. Figure 3c shows a thin but complete circumferential coat of smooth muscle cells in the artery wall that is most strongly visible where the artery is cut in transverse section. The completeness of the smooth muscle coat allows arteries to be distinguished from veins that have only occasional smooth muscle cells in their walls. Basement membrane staining for laminin and Aβ is associated with the smooth muscle cell layer (Fig. 3d). These images support previously published data [7] showing fluorescent tracers within the basement membranes of the tunica media of cerebral arteries. No tracer was observed in association with veins.Fig. 3


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)

Immunocytochemistry/confocal images showing that 5 min after the injection of soluble Aβ into the hippocampus, Aβ is associated with basement membrane proteins within the wall of an artery in the hippocampal fissure. a Aβ (red) in the wall of a leptomeningeal artery; b laminin (blue); c a layer of smooth muscle cells (green) in the artery wall that is most clearly seen when the vessel is cut in cross section; d a merged image showing co-localisation of Aβ and laminin (purple–see arrows) associated with the smooth muscle cells. The outermost layer of the artery, the tunica adventitia (ta), is stained only for laminin (blue) and not for Aβ. SP5 Leica confocal image. Scale bar 50 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Immunocytochemistry/confocal images showing that 5 min after the injection of soluble Aβ into the hippocampus, Aβ is associated with basement membrane proteins within the wall of an artery in the hippocampal fissure. a Aβ (red) in the wall of a leptomeningeal artery; b laminin (blue); c a layer of smooth muscle cells (green) in the artery wall that is most clearly seen when the vessel is cut in cross section; d a merged image showing co-localisation of Aβ and laminin (purple–see arrows) associated with the smooth muscle cells. The outermost layer of the artery, the tunica adventitia (ta), is stained only for laminin (blue) and not for Aβ. SP5 Leica confocal image. Scale bar 50 μm
Mentions: To demonstrate that soluble Aβ injected into the hippocampus reaches leptomeningeal arteries 5 min after injection, sections of brain were examined by immunocytochemistry and confocal microscopy. Figure 3 shows a series of confocal images that depict staining for Aβ, basement membrane laminin and smooth muscle actin. The leptomeningeal artery in Fig. 3 is seen as a cylinder viewed obliquely and end-on. Aβ (Fig. 3a) has a similar pattern of staining in the vessel wall to laminin (Fig. 3b) but not exactly the same. Differences can be detected in the merged image (Fig. 3d); although Aβ merges with laminin throughout the length of the section of the vessel wall, the tunica adventitia on the outer aspect of the artery stains for laminin but is devoid of Aβ. Figure 3c shows a thin but complete circumferential coat of smooth muscle cells in the artery wall that is most strongly visible where the artery is cut in transverse section. The completeness of the smooth muscle coat allows arteries to be distinguished from veins that have only occasional smooth muscle cells in their walls. Basement membrane staining for laminin and Aβ is associated with the smooth muscle cell layer (Fig. 3d). These images support previously published data [7] showing fluorescent tracers within the basement membranes of the tunica media of cerebral arteries. No tracer was observed in association with veins.Fig. 3

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