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Blood–brain barrier and blood–cerebrospinal fluid barrier in normal and pathological conditions

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Abstract

Blood-borne substances can invade into the extracellular spaces of the brain via endothelial cells in sites without the blood–brain barrier (BBB), and can travel through the interstitial fluid (ISF) of the brain parenchyma adjacent to non-BBB sites. It has been shown that cerebrospinal fluid (CSF) drains directly into the blood via the arachnoid villi and also into lymph nodes via the subarachnoid spaces of the brain, while ISF drains into the cervical lymph nodes through perivascular drainage pathways. In addition, the glymphatic pathway of fluids, characterized by para-arterial pathways, aquaporin4-dependent passage through astroglial cytoplasm, interstitial spaces, and paravenous routes, has been established. Meningeal lymphatic vessels along the superior sagittal sinus were very recently discovered. It is known that, in mice, blood-borne substances can be transferred to areas with intact BBB function, such as the medial regions of the hippocampus, presumably through leaky vessels in non-BBB sites. In the present paper, we review the clearance mechanisms of interstitial substances, such as amyloid-β peptides, as well as summarize models of BBB deterioration in response to different types of insults, including acute ischemia followed by reperfusion, hypertension, and chronic hypoperfusion. Lastly, we discuss the relationship between perivascular clearance and brain disorders.

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Abbreviations

ABC:

ATP-binding cassette

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

BBB:

Blood–brain barrier

BCSFB:

Blood–cerebrospinal fluid barrier

CAA:

Cerebral amyloid angiopathy

CSF:

Cerebrospinal fluid

FPRL1:

Formylpeptide receptor-like-1

IDE:

Insulin-degrading enzyme

ISF:

Interstitial fluid

LDLR:

Low-density-lipoprotein receptor

LRP:

LDLR-related protein

MRI:

Magnetic resonance imaging

NMO:

Neuromyelitis optica

P-gp:

P-glycoprotein

RAGE:

Receptor for advanced glycation end product

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Acknowledgments

This study was supported by a Grant-in-aid for Scientific Research (C) 26430055 (M.U.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank Ms. K. Yasutomi for editorial assistance.

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Authors and Affiliations

  1. Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Masaki Ueno, Yoichi Chiba, Ryuta Murakami, Koichi Matsumoto, Machi Kawauchi & Ryuji Fujihara

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  1. Masaki Ueno
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  2. Yoichi Chiba
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Correspondence to Masaki Ueno.

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Ueno, M., Chiba, Y., Murakami, R. et al. Blood–brain barrier and blood–cerebrospinal fluid barrier in normal and pathological conditions. Brain Tumor Pathol 33, 89–96 (2016). https://doi.org/10.1007/s10014-016-0255-7

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