Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2017

Open Access 01-12-2017 | Editorial

Brain barriers and brain fluid research in 2016: advances, challenges and controversies

Authors: Richard F. Keep, Hazel C. Jones, Lester R. Drewes

Published in: Fluids and Barriers of the CNS | Issue 1/2017

Login to get access

Abstract

This editorial highlights some of the advances that occurred in relation to brain barriers and brain fluid research in 2016. It also aims to raise some of the attendant controversies and challenges in such research.
Literature
1.
Deverman BE, Pravdo PL, Simpson BP, Kumar SR, Chan KY, Banerjee A, Wu WL, Yang B, Huber N, Pasca SP, et al. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat Biotechnol. 2016;34(2):204–9.CrossRefPubMedPubMedCentral
2.
Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–6.CrossRefPubMed
3.
Chu PC, Chai WY, Tsai CH, Kang ST, Yeh CK, Liu HL. Focused Ultrasound-induced blood–brain barrier opening: association with mechanical index and cavitation index analyzed by dynamic contrast-enhanced magnetic-resonance imaging. Sci Rep. 2016;6:33264.CrossRefPubMedPubMedCentral
4.
Samiotaki G, Karakatsani ME, Buch A, Papadopoulos S, Wu SY, Jambawalikar S, Konofagou EE. Pharmacokinetic analysis and drug delivery efficiency of the focused ultrasound-induced blood–brain barrier opening in non-human primates. Magn Reson Imaging. 2016;37:273–81.CrossRefPubMed
5.
Wu SY, Sanchez CS, Samiotaki G, Buch A, Ferrera VP, Konofagou EE. Characterizing focused-ultrasound mediated drug delivery to the heterogeneous primate brain in vivo with acoustic monitoring. Sci Rep. 2016;6:37094.CrossRefPubMedPubMedCentral
6.
Cho H, Lee HY, Han M, Choi JR, Ahn S, Lee T, Chang Y, Park J. Localized down-regulation of P-glycoprotein by focused ultrasound and microbubbles induced blood–brain barrier disruption in rat brain. Sci Rep. 2016;6:31201.CrossRefPubMedPubMedCentral
7.
Gaillard PJ. BBB crossing assessment and BBB crossing technologies in CNS drug discovery. Drug Discov Today Technol. 2016;20:1–3.CrossRefPubMed
8.
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4(147):147ra111.CrossRefPubMedPubMedCentral
9.
Hladky SB, Barrand MA. Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS. 2014;11(1):26.CrossRefPubMedPubMedCentral
10.
11.
12.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, et al. Sleep drives metabolite clearance from the adult brain. Science (New York, NY). 2013;342(6156):373–7.CrossRef
13.
Wostyn P, Van Dam D, Audenaert K, Killer HE, De Deyn PP, De Groot V. A new glaucoma hypothesis: a role of glymphatic system dysfunction. Fluids Barriers CNS. 2015;12:16.CrossRefPubMedPubMedCentral
14.
Kiviniemi V, Wang X, Korhonen V, Keinanen T, Tuovinen T, Autio J, LeVan P, Keilholz S, Zang YF, Hennig J, et al. Ultra-fast magnetic resonance encephalography of physiological brain activity—glymphatic pulsation mechanisms? J Cereb Blood Flow Metab. 2016;36(6):1033–45.CrossRefPubMed
15.
Zong X, Park SH, Shen D, Lin W. Visualization of perivascular spaces in the human brain at 7T: sequence optimization and morphology characterization. NeuroImage. 2016;125:895–902.CrossRefPubMed
16.
17.
Jin BJ, Smith AJ, Verkman AS. Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism. J Gen Physiol. 2016;148(6):489–501.CrossRefPubMed
18.
19.
Hladky SB, Barrand MA. Fluid and ion transfer across the blood–brain and blood-cerebrospinal fluid barriers; a comparative account of mechanisms and roles. Fluids Barriers CNS. 2016;13(1):19.CrossRefPubMed
20.
Spector R, Keep RF, Robert Snodgrass S, Smith QR, Johanson CE. A balanced view of choroid plexus structure and function: focus on adult humans. Exp Neurol. 2015;267:78–86.CrossRefPubMed
21.
Oreskovic D, Rados M, Klarica M. New concepts of cerebrospinal fluid physiology and development of hydrocephalus. Pediatr Neurosurg. 2016; doi:10.​1159/​000452169. [Epub ahead of print].PubMed
22.
Yamada S, Kelly E. Cerebrospinal fluid dynamics and the pathophysiology of hydrocephalus: new concepts. Semin Ultrasound CT MR. 2016;37(2):84–91.CrossRefPubMed
23.
Dreha-Kulaczewski S, Joseph AA, Merboldt KD, Ludwig HC, Gartner J, Frahm J. Inspiration is the major regulator of human CSF flow. J Neurosci. 2015;35(6):2485–91.CrossRefPubMed
24.
Faubel R, Westendorf C, Bodenschatz E, Eichele G. Cilia-based flow network in the brain ventricles. Science (New York, NY). 2016;353(6295):176–8.CrossRef
25.
Hakvoort A, Haselbach M, Galla HJ. Active transport properties of porcine choroid plexus cells in culture. Brain Res. 1998;795(1–2):247–56.CrossRefPubMed
26.
O’Donnell ME. Blood–brain barrier Na transporters in ischemic stroke. Adv Pharmacol (San Diego, Calif). 2014;71:113–46.CrossRef
27.
Strazielle N, Creidy R, Malcus C, Boucraut J, Ghersi-Egea JF. T-lymphocytes traffic into the brain across the blood-CSF barrier: evidence using a reconstituted choroid plexus epithelium. PLoS ONE. 2016;11(3):e0150945.CrossRefPubMedPubMedCentral
28.
Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F. Age-dependent niche signals from the choroid plexus regulate adult neural stem cells. Cell Stem Cell. 2016;19(5):643–52.CrossRefPubMed
29.
Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, Brkic M, Demeestere D, Vanhooren V, Hendrix A, et al. Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol Med. 2016;8(10):1162–83.CrossRefPubMedPubMedCentral
30.
Strazielle N, Ghersi-Egea JF. Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier. Curr Pharm Des. 2016;22(35):5463–76.CrossRefPubMed
31.
Yung YC, Mutoh T, Lin ME, Noguchi K, Rivera RR, Choi JW, Kingsbury MA, Chun J. Lysophosphatidic acid signaling may initiate fetal hydrocephalus. Science Transl Med. 2011;3:99ra87.CrossRef
32.
Park R, Moon UY, Park JY, Hughes LJ, Johnson RL, Cho SH, Kim S. Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus. Nat Commun. 2016;7:10329.CrossRefPubMedPubMedCentral
33.
34.
Foerster P, Daclin M, Asm S, Faucourt M, Boletta A, Genovesio A, Spassky N. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development. 2017;144(2):201–10.CrossRefPubMed
35.
Wang X, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, Zheng Q, Gao Y, Luo H, Zhang X, et al. SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis. J Neurosci. 2016;36(50):12586–97.CrossRefPubMed
36.
37.
Keong NC, Pena A, Price SJ, Czosnyka M, Czosnyka Z, Pickard JD. Imaging normal pressure hydrocephalus: theories, techniques, and challenges. Neurosurg Focus. 2016;41(3):E11.CrossRefPubMed
38.
Djukic M, Spreer A, Lange P, Bunkowski S, Wiltfang J, Nau R. Small cisterno-lumbar gradient of phosphorylated Tau protein in geriatric patients with suspected normal pressure hydrocephalus. Fluids Barriers CNS. 2016;13(1):15.CrossRefPubMedPubMedCentral
39.
Ishikawa M, Yamada S, Yamamoto K. Early and delayed assessments of quantitative gait measures to improve the tap test as a predictor of shunt effectiveness in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS. 2016;13(1):20.CrossRefPubMedPubMedCentral
40.
Luikku AJ, Hall A, Nerg O, Koivisto AM, Hiltunen M, Helisalmi S, Herukka SK, Sutela A, Kojoukhova M, Mattila J, et al. Multimodal analysis to predict shunt surgery outcome of 284 patients with suspected idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2016;158(12):2311–9.CrossRef
41.
Aojula A, Botfield H, McAllister JP 2nd, Gonzalez AM, Abdullah O, Logan A, Sinclair A. Diffusion tensor imaging with direct cytopathological validation: characterisation of decorin treatment in experimental juvenile communicating hydrocephalus. Fluids Barriers CNS. 2016;13(1):9.CrossRefPubMedPubMedCentral
42.
Kanno S, Saito M, Kashinoura T, Nishio Y, Iizuka O, Kikuchi H, Takagi M, Iwasaki M, Takahashi S, Mori E. A change in brain white matter after shunt surgery in idiopathic normal pressure hydrocephalus: a tract-based spatial statistics study. Fluids Barriers CNS. 2017. doi:10.​1186/​s12987-016-0048-8. (this issue)PubMed
43.
Shi Y, Zhang L, Pu H, Mao L, Hu X, Jiang X, Xu N, Stetler RA, Zhang F, Liu X, et al. Rapid endothelial cytoskeletal reorganization enables early blood–brain barrier disruption and long-term ischaemic reperfusion brain injury. Nat Commun. 2016;7:10523.CrossRefPubMedPubMedCentral
44.
Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet (London, England). 2016;387(10029):1723–31.CrossRef
45.
Wahlgren N, Thoren M, Hojeberg B, Kall TB, Laska AC, Sjostrand C, Hoijer J, Almqvist H, Holmin S, Lilja A, et al. Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis. J Intern Med. 2016;. doi:10.​1111/​joim.​12576. [ Epub ahead of print]PubMed
46.
Merali Z, Leung J, Mikulis D, Silver F, Kassner A. Longitudinal assessment of imatinib’s effect on the blood–brain barrier after ischemia/reperfusion injury with permeability MRI. Transl Stroke Res. 2015;6(1):39–49.CrossRefPubMed
47.
Su EJ, Fredriksson L, Geyer M, Folestad E, Cale J, Andrae J, Gao Y, Pietras K, Mann K, Yepes M, et al. Activation of PDGF-CC by tissue plasminogen activator impairs blood–brain barrier integrity during ischemic stroke. Nat Med. 2008;14(7):731–7.CrossRefPubMedPubMedCentral
48.
Leen WG, Taher M, Verbeek MM, Kamsteeg EJ, van de Warrenburg BP, Willemsen MA. GLUT1 deficiency syndrome into adulthood: a follow-up study. J Neurol. 2014;261(3):589–99.CrossRefPubMed
49.
Tarlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481–94.CrossRefPubMed
50.
Zetterberg H, Blennow K. Fluid biomarkers for mild traumatic brain injury and related conditions. Nat Rev Neurol. 2016;12(10):563–74.CrossRefPubMed
51.
Dadas A, Washington J, Marchi N, Janigro D. Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers. Fluids Barriers CNS. 2016;13(1):21.CrossRefPubMed
52.
Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, Abramova N, Vincent P, Pumiglia K, Temple S. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science (New York, NY). 2004;304(5675):1338–40.CrossRef
53.
Gilbertson RJ, Rich JN. Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer. 2007;7(10):733–6.CrossRefPubMed
54.
Yadav VN, Zamler D, Baker GJ, Kadiyala P, Erdreich-Epstein A, DeCarvalho AC, Mikkelsen T, Castro MG, Lowenstein PR. CXCR4 increases in vivo glioma perivascular invasion, and reduces radiation induced apoptosis: a genetic knockdown study. Oncotarget. 2016. (in press)
55.
Helms HC, Abbott NJ, Burek M, Cecchelli R, Couraud PO, Deli MA, Forster C, Galla HJ, Romero IA, Shusta EV, et al. In vitro models of the blood–brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab. 2016;36(5):862–90.CrossRefPubMed
56.
Canfield SG, Stebbins MJ, Morales BS, Asai SW, Vatine GD, Svendsen CN, Palecek SP, Shusta EV. An isogenic blood–brain barrier model comprising brain endothelial cells, astrocytes and neurons derived from human induced pluripotent stem cells. J Neurochem. 2016;. doi:10.​1111/​jnc.​13923. [Epub ahead of print]PubMed
57.
Adriani G, Ma D, Pavesi A, Kamm RD, Goh EL. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood–brain barrier. Lab Chip. 2016;. doi:10.​1039/​c6lc00638h. [Epub ahead of print]
58.
Tourovskaia A, Fauver M, Kramer G, Simonson S, Neumann T. Tissue-engineered microenvironment systems for modeling human vasculature. Exp Biol Med (Maywood, NJ). 2014;239(9):1264–71.CrossRef
59.
van der Helm MW, van der Meer AD, Eijkel JC, van den Berg A, Segerink LI. Microfluidic organ-on-chip technology for blood–brain barrier research. Tissue Barriers. 2016;4(1):e1142493.CrossRefPubMedPubMedCentral
60.
Wang YI, Abaci HE, Shuler ML. Microfluidic blood–brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017;114(1):184–94.CrossRefPubMed
Metadata
Title
Brain barriers and brain fluid research in 2016: advances, challenges and controversies
Authors
Richard F. Keep
Hazel C. Jones
Lester R. Drewes
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2017
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-017-0052-7

Other articles of this Issue 1/2017

Fluids and Barriers of the CNS 1/2017 Go to the issue

Research

A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets

Research

Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses

Erratum

Erratum to: The Wisconsin Hydrocephalus Survey: shunt-dependent hydrocephalus management style among members of the American Society of Pediatric Neurosurgeons

Review

The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse

Review

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017

Research

Hyperdynamic CSF motion profiles found in idiopathic normal pressure hydrocephalus and Alzheimer’s disease assessed by fluid mechanics derived from magnetic resonance images