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Fluids and Barriers of the CNS

Joao Prola Netto, Daniel Schwartz, Csanad Varallyay, Rongwei Fu, Bronwyn Hamilton, Edward A Neuwelt
BACKGROUND: Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management. METHODS: 16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included...
December 20, 2016: Fluids and Barriers of the CNS
Naoko H Tomioka, Yoshifuru Tamura, Tappei Takada, Shigeru Shibata, Hiroshi Suzuki, Shunya Uchida, Makoto Hosoyamada
BACKGROUND: Uric acid (UA) is known to exert neuroprotective effects in the brain. However, the mechanism of UA regulation in the brain is not well characterized. In our previous study, we described that the mouse urate transporter URAT1 is localized to the cilia and apical surface of ventricular ependymal cells. To further strengthen the hypothesis that UA is transported transcellularly at the ependymal cells, we aimed to assess the distribution of other UA transporters in the murine brain...
December 12, 2016: Fluids and Barriers of the CNS
Aaron Dadas, Jolewis Washington, Nicola Marchi, Damir Janigro
BACKGROUND: Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence on variables other than the disease condition itself. These include half-life in blood, molecular weight, and marker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To study these factors, and to provide a method for markers' analyses, we developed a kinetic model that allows the integrated interpretation of these properties...
November 30, 2016: Fluids and Barriers of the CNS
Masatsune Ishikawa, Shigeki Yamada, Kazuo Yamamoto
BACKGROUND: To improve the diagnostic performance of the cerebrospinal fluid (CSF) tap test (TT), early and delayed assessments of gait were performed after the removal of 30 ml of CSF in patients with probable idiopathic normal pressure hydrocephalus. Assessments of gait included the 3-m timed up and go test (TUG), and the 10-m walk in time (10Ti) and in step (10St) tests. METHODS: Quantitative data for the TUG, the 10Ti, and the 10St were obtained before CSF removal and on days 1 and 4 after removal of 30 ml CSF...
November 22, 2016: Fluids and Barriers of the CNS
Stephen B Hladky, Margery A Barrand
The two major interfaces separating brain and blood have different primary roles. The choroid plexuses secrete cerebrospinal fluid into the ventricles, accounting for most net fluid entry to the brain. Aquaporin, AQP1, allows water transfer across the apical surface of the choroid epithelium; another protein, perhaps GLUT1, is important on the basolateral surface. Fluid secretion is driven by apical Na(+)-pumps. K(+) secretion occurs via net paracellular influx through relatively leaky tight junctions partially offset by transcellular efflux...
October 31, 2016: Fluids and Barriers of the CNS
Shyanne Page, Alli Munsell, Abraham J Al-Ahmad
BACKGROUND: Cerebral hypoxia/ischemia (H/I) is an important stress factor involved in the disruption of the blood-brain barrier (BBB) following stroke injury, yet the cellular and molecular mechanisms on how the human BBB responds to such injury remains unclear. In this study, we investigated the cellular response of the human BBB to chemical and environmental H/I in vitro. METHODS: In this study, we used immortalized hCMEC/D3 and IMR90 stem-cell derived human brain microvascular endothelial cell lines (IMR90-derived BMECs)...
October 11, 2016: Fluids and Barriers of the CNS
Marija Djukic, Annette Spreer, Peter Lange, Stephanie Bunkowski, Jens Wiltfang, Roland Nau
BACKGROUND: The composition of the cerebrospinal fluid (CSF) is not homogeneous, and concentrations of proteins from different origins diverge among ventricular, cisternal and lumbar CSF fractions. Concentrations of blood-derived proteins increase and of brain-derived proteins decrease from ventricular to lumbar fractions. We studied whether the origin of the CSF portion analysed may affect results in CSF analysis for dementia. METHODS: In 16 geriatric patients with suspected normal pressure hydrocephalus [age 82...
August 31, 2016: Fluids and Barriers of the CNS
B Shackleton, F Crawford, C Bachmeier
BACKGROUND: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of Aβ in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and Aβ transit across the BBB...
August 8, 2016: Fluids and Barriers of the CNS
A Jeppsson, Mikko Höltta, H Zetterberg, K Blennow, C Wikkelsø, Mats Tullberg
BACKGROUND: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) and α- and β-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPβ). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery...
July 29, 2016: Fluids and Barriers of the CNS
Erin Gallagher, Il Minn, Janice E Chambers, Peter C Searson
BACKGROUND: Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. METHODS: To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)...
July 11, 2016: Fluids and Barriers of the CNS
Ryann M Fame, Jessica T Chang, Alex Hong, Nicole A Aponte-Santiago, Hazel Sive
BACKGROUND: Cerebrospinal fluid (CSF) contained within the brain ventricles contacts neuroepithelial progenitor cells during brain development. Dynamic properties of CSF movement may limit locally produced factors to specific regions of the developing brain. However, there is no study of in vivo CSF dynamics between ventricles in the embryonic brain. We address CSF movement using the zebrafish larva, during the major period of developmental neurogenesis. METHODS: CSF movement was monitored at two stages of zebrafish development: early larva [pharyngula stage; 27-30 h post-fertilization (hpf)] and late larva (hatching period; 51-54 hpf) using photoactivatable Kaede protein to calculate average maximum CSF velocity between ventricles...
June 21, 2016: Fluids and Barriers of the CNS
Anuriti Aojula, Hannah Botfield, James Patterson McAllister, Ana Maria Gonzalez, Osama Abdullah, Ann Logan, Alexandra Sinclair
BACKGROUND: In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Furthermore, the capacity for diffusion tensor imaging to act as a proxy measure of cerebral pathology in multiple sclerosis and spinal cord injury has recently been demonstrated...
May 31, 2016: Fluids and Barriers of the CNS
Camilla Cerutti, Patricia Soblechero-Martin, Dongsheng Wu, Miguel Alejandro Lopez-Ramirez, Helga de Vries, Basil Sharrack, David Kingsley Male, Ignacio Andres Romero
BACKGROUND: Increased leukocyte adhesion to brain endothelial cells forming the blood-brain barrier (BBB) precedes extravasation into the central nervous system (CNS) in neuroinflammatory diseases such as multiple sclerosis (MS). Previously, we reported that microRNA-155 (miR-155) is up-regulated in MS and by inflammatory cytokines in human brain endothelium, with consequent modulation of endothelial paracellular permeability. Here, we investigated the role of endothelial miR-155 in leukocyte adhesion to the human cerebral microvascular endothelial cell line, hCMEC/D3, under shear forces mimicking blood flow in vivo...
May 31, 2016: Fluids and Barriers of the CNS
Domenico L Di Curzio, Emily Turner-Brannen, Xiaoyan Mao, Marc R Del Bigio
BACKGROUND: Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO4). We hypothesized that MgSO4 therapy would improve outcomes in ferrets with hydrocephalus induced with kaolin at 15 days. METHODS: MRI was performed at 29 days to assess ventricle size and stratify ferrets to treatment conditions. Beginning at 31 days age, they were treated daily for 14 days with MgSO4 (9 mM/kg/day) or sham saline therapy, and then imaged again before sacrifice...
April 27, 2016: Fluids and Barriers of the CNS
Ronak Patel, Abraham J Alahmad
BACKGROUND: Patient-derived induced pluripotent stem cells (iPSCs) are an innovative source as an in vitro model for neurological diseases. Recent studies have demonstrated the differentiation of brain microvascular endothelial cells (BMECs) from various stem cell sources, including iPSC lines. However, the impact of the culturing conditions used to maintain such stem cell pluripotency on their ability to differentiate into BMECs remains undocumented. In this study, we investigated the effect of different sources of Matrigel and stem cell maintenance medium on BMEC differentiation efficiency...
April 12, 2016: Fluids and Barriers of the CNS
David Bueno, Jordi Garcia-Fernàndez
Within the consolidated field of evolutionary development, there is emerging research on evolutionary aspects of central nervous system development and its implications for adult brain structure and function, including behaviour. The central nervous system is one of the most intriguing systems in complex metazoans, as it controls all body and mind functions. Its failure is responsible for a number of severe and largely incurable diseases, including neurological and neurodegenerative ones. Moreover, the evolution of the nervous system is thought to be a critical step in the adaptive radiation of vertebrates...
March 15, 2016: Fluids and Barriers of the CNS
Elias Johansson, Khalid Ambarki, Richard Birgander, Nazila Bahrami, Anders Eklund, Jan Malm
BACKGROUND: A vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH. METHODS: In this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence...
February 10, 2016: Fluids and Barriers of the CNS
Marc R Del Bigio, Domenico L Di Curzio
Pharmacological interventions have been tested experimentally and clinically to prevent hydrocephalus and avoid the need for shunting beginning in the 1950s. Clinical trials of varied quality have not demonstrated lasting and convincing protective effects through manipulation of cerebrospinal fluid production, diuresis, blood clot fibrinolysis, or manipulation of fibrosis in the subarachnoid compartment, although there remains some promise in the latter areas. Acetazolamide bolus seems to be useful for predicting shunt response in adults with hydrocephalus...
February 5, 2016: Fluids and Barriers of the CNS
Ivana Lazarevic, Britta Engelhardt
BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) established by the choroid plexus (CP) epithelium has been recognized as a potential entry site of immune cells into the central nervous system during immunosurveillance and neuroinflammation. The location of the choroid plexus impedes in vivo analysis of immune cell trafficking across the BCSFB. Thus, research on cellular and molecular mechanisms of immune cell migration across the BCSFB is largely limited to in vitro models. In addition to forming contact-inhibited epithelial monolayers that express adhesion molecules, the optimal in vitro model must establish a tight permeability barrier as this influences immune cell diapedesis...
January 29, 2016: Fluids and Barriers of the CNS
Lester R Drewes, Hazel C Jones, Richard F Keep
Research into brain barriers and brain fluids has been advancing rapidly in recent years. This editorial aims to highlight some of the advances that have improved our understanding of this complex subject. It also brings you news of developments for Fluids and Barriers of the CNS including a new affiliation between the journal and the International Society for Hydrocephalus and CSF disorders.
January 28, 2016: Fluids and Barriers of the CNS
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