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Fluids and Barriers of the CNS

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https://www.readbyqxmd.com/read/29759080/zika-virus-crosses-an-in-vitro-human-blood-brain-barrier-model
#1
Judie B Alimonti, Maria Ribecco-Lutkiewicz, Caroline Sodja, Anna Jezierski, Danica B Stanimirovic, Qing Liu, Arsalan S Haqqani, Wayne Conlan, Mahmud Bani-Yaghoub
Zika virus (ZIKV) is a flavivirus that is highly neurotropic causing congenital abnormalities and neurological damage to the central nervous systems (CNS). In this study, we used a human induced pluripotent stem cell (iPSC)-derived blood brain barrier (BBB) model to demonstrate that ZIKV can infect brain endothelial cells (i-BECs) without compromising the BBB barrier integrity or permeability. Although no disruption to the BBB was observed post-infection, ZIKV particles were released on the abluminal side of the BBB model and infected underlying iPSC-derived neural progenitor cells (i-NPs)...
May 15, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29720231/nimodipine-treatment-does-not-benefit-juvenile-ferrets-with-kaolin-induced-hydrocephalus
#2
Domenico L Di Curzio, Xiaoyan Mao, Aidan Baker, Marc R Del Bigio
Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca2+ channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness...
May 3, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29704892/fluid-outflow-in-the-rat-spinal-cord-the-role-of-perivascular-and-paravascular-pathways
#3
Shinuo Liu, Magdalena A Lam, Alisha Sial, Sarah J Hemley, Lynne E Bilston, Marcus A Stoodley
BACKGROUND: Cerebrospinal fluid (CSF) is thought to flow into the brain via perivascular spaces around arteries, where it mixes with interstitial fluid. The precise details concerning fluid outflow remain controversial. Although fluid dynamics have been studied in the brain, little is known about spinal cord fluid inflow and outflow. Understanding the normal fluid physiology of the spinal cord may give insight into the pathogenesis of spinal cord oedema and CSF disorders such as syringomyelia...
April 29, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29688865/brain-vascular-heterogeneity-implications-for-disease-pathogenesis-and-design-of-in-vitro-blood-brain-barrier-models
#4
REVIEW
Midrelle E Noumbissi, Bianca Galasso, Monique F Stins
The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter...
April 23, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29615068/modeling-and-rescue-of-defective-blood-brain-barrier-function-of-induced-brain-microvascular-endothelial-cells-from-childhood-cerebral-adrenoleukodystrophy-patients
#5
Catherine A A Lee, Hannah S Seo, Anibal G Armien, Frank S Bates, Jakub Tolar, Samira M Azarin
BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene. 40% of X-ALD patients will convert to the deadly childhood cerebral form (ccALD) characterized by increased permeability of the brain endothelium that constitutes the blood-brain barrier (BBB). Mutation information and molecular markers investigated to date are not predictive of conversion. Prior reports have focused on toxic metabolic byproducts and reactive oxygen species as instigators of cerebral inflammation and subsequent immune cell invasion leading to BBB breakdown...
April 4, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29587767/opportunities-in-posthemorrhagic-hydrocephalus-research-outcomes-of-the-hydrocephalus-association-posthemorrhagic-hydrocephalus-workshop
#6
REVIEW
Jenna E Koschnitzky, Richard F Keep, David D Limbrick, James P McAllister, Jill A Morris, Jennifer Strahle, Yun C Yung
The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on July 25 and 26, 2016 at the National Institutes of Health. The workshop brought together a diverse group of researchers including pediatric neurosurgeons, neurologists, and neuropsychologists with scientists in the fields of brain injury and development, cerebrospinal and interstitial fluid dynamics, and the blood-brain and blood-CSF barriers. The goals of the workshop were to identify areas of opportunity in posthemorrhagic hydrocephalus research and encourage scientific collaboration across a diverse set of fields...
March 27, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29558954/monoclonal-antibody-exposure-in-rat-and-cynomolgus-monkey-cerebrospinal-fluid-following-systemic-administration
#7
Qin Wang, Luisette Delva, Paul H Weinreb, Robert B Pepinsky, Danielle Graham, Elvana Veizaj, Anne E Cheung, Weiping Chen, Ivan Nestorov, Ellen Rohde, Robin Caputo, Geoffrey M Kuesters, Tonika Bohnert, Liang-Shang Gan
BACKGROUND: Many studies have focused on the challenges of small molecule uptake across the blood-brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (CNS). In drug development, cerebrospinal fluid (CSF) sampling is routinely used as a surrogate for assessing CNS drug exposure and biomarker levels. In this report, we have studied the kinetic correlation between CSF and serum drug concentration-time profiles for five humanized monoclonal antibodies in rats and cynomolgus monkeys and analyzed factors that affect their CSF exposure...
March 20, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29540199/cerebrospinal-fluid-protein-and-glucose-levels-in-neonates-with-a-systemic-inflammatory-response-without-meningitis
#8
Mona Noureldein, Roxana Mardare, Jack Pickard, Hoi Lun Shing, Michael Eisenhut
BACKGROUND: It has been estimated that paediatric meningitis without elevated CSF white cell count (pleocytosis) accounts for 0.5-12% of all cases of bacterial meningitis. CSF protein and glucose measurements are therefore essential in management but may be neglected in clinical practice. In order to improve recognition of bacterial meningitis in neonates and to enable adequate management and audit, we investigated whether a systemic inflammatory response in the absence of meningitis is associated with elevated CSF protein and reduced CSF glucose levels...
March 14, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29463314/functional-brain-specific-microvessels-from-ipsc-derived-human-brain-microvascular-endothelial-cells-the-role-of-matrix-composition-on-monolayer-formation
#9
Moriah E Katt, Raleigh M Linville, Lakyn N Mayo, Zinnia S Xu, Peter C Searson
BACKGROUND: Transwell-based models of the blood-brain barrier (BBB) incorporating monolayers of human brain microvascular endothelial cells (dhBMECs) derived from induced pluripotent stem cells show many of the key features of the BBB, including expression of transporters and efflux pumps, expression of tight junction proteins, and physiological values of transendothelial electrical resistance. The fabrication of 3D BBB models using dhBMECs has so far been unsuccessful due to the poor adhesion and survival of these cells on matrix materials commonly used in tissue engineering...
February 20, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29422104/paradigm-shift-radiological-changes-in-the-asymptomatic-inph-patient-to-be-an-observational-study
#10
D C Engel, S D Adib, M U Schuhmann, C Brendle
BACKGROUND: Many radiological signs are known for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH). However, there is little information about these signs in the pre-symptomatic phase. For pathophysiological investigative purposes we conducted a descriptive image analysis study on pre-symptomatic patients. METHODS: Patients that had contact with either the neurological or neurosurgical department of the university hospital Tuebingen from 2010 through 2016 with magnetic resonance images > 3 years before onset of symptoms, were included...
February 9, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29391031/progress-in-brain-barriers-and-brain-fluid-research-in-2017
#11
EDITORIAL
Richard F Keep, Hazel C Jones, Lester R Drewes
The past year, 2017, has seen many important papers published in the fields covered by Fluids and Barriers of the CNS. This article from the Editors highlights some.
February 2, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29332604/the-effect-of-an-adenosine-a-2a-agonist-on-intra-tumoral-concentrations-of-temozolomide-in-patients-with-recurrent-glioblastoma
#12
Sadhana Jackson, Jon Weingart, Edjah K Nduom, Thura T Harfi, Richard T George, Dorothea McAreavey, Xiaobu Ye, Nicole M Anders, Cody Peer, William D Figg, Mark Gilbert, Michelle A Rudek, Stuart A Grossman
BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma. METHODS: Patients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible...
January 15, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29329565/correction-to-current-research-into-brain-barriers-and-the-delivery-of-therapeutics-for-neurological-diseases-a-report-on-cns-barrier-congress-london-uk-2017
#13
John Greenwood, Margareta Hammarlund-Udenaes, Hazel C Jones, Alan W Stitt, Roosmarijn E Vandenbroucke, Ignacio A Romero, Matthew Campbell, Gert Fricker, Birger Brodin, Heiko Manninga, Pieter J Gaillard, Markus Schwaninger, Carl Webster, Krzysztof B Wicher, Michel Khrestchatisky
After publication of the article [1], it has been brought to our attention that there are some errors in the formatting of names in the final version of the article.
January 12, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29307307/role-of-cationic-drug-sensitive-transport-systems-at-the-blood-cerebrospinal-fluid-barrier-in-para-tyramine-elimination-from-rat-brain
#14
Shin-Ichi Akanuma, Yuhei Yamazaki, Yoshiyuki Kubo, Ken-Ichi Hosoya
BACKGROUND: para-Tyramine (p-TA) is a biogenic amine which is involved in multiple neuronal signal transductions. Since the concentration of p-TA in dog cerebrospinal fluid (CSF) has been reported to be greater than that in plasma, it is proposed that clearance of cerebral p-TA is important for normal function. The purpose of this study was to examine the role of the blood-brain barrier and blood-cerebrospinal fluid barrier (BCSFB) in p-TA clearance from the brain. METHODS: In vivo [3 H]p-TA elimination from rat cerebral cortex and from CSF was examined after intracerebral and intracerebroventricular administration, respectively...
January 8, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29258534/a-3d-subject-specific-model-of-the-spinal-subarachnoid-space-with-anatomically-realistic-ventral-and-dorsal-spinal-cord-nerve-rootlets
#15
Lucas R Sass, Mohammadreza Khani, Gabryel Connely Natividad, R Shane Tubbs, Olivier Baledent, Bryn A Martin
BACKGROUND: The spinal subarachnoid space (SSS) has a complex 3D fluid-filled geometry with multiple levels of anatomic complexity, the most salient features being the spinal cord and dorsal and ventral nerve rootlets. An accurate anthropomorphic representation of these features is needed for development of in vitro and numerical models of cerebrospinal fluid (CSF) dynamics that can be used to inform and optimize CSF-based therapeutics. METHODS: A subject-specific 3D model of the SSS was constructed based on high-resolution anatomic MRI...
December 19, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29228970/chemokine-and-cytokine-levels-in-the-lumbar-cerebrospinal-fluid-of-preterm-infants-with-post-hemorrhagic-hydrocephalus
#16
Gakwaya Habiyaremye, Diego M Morales, Clinton D Morgan, James P McAllister, Travis S CreveCoeur, Rowland H Han, Mohamed Gabir, Brandon Baksh, Deanna Mercer, David D Limbrick
BACKGROUND: Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). METHODS: Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury...
December 12, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29212505/do-patients-with-schizophreniform-and-bipolar-disorders-show-an-intrathecal-polyspecific-antiviral-immune-response-a-pilot-study
#17
Dominique Endres, Daniela Huzly, Rick Dersch, Oliver Stich, Benjamin Berger, Florian Schuchardt, Evgeniy Perlov, Nils Venhoff, Sabine Hellwig, Bernd L Fiebich, Daniel Erny, Tilman Hottenrott, Ludger Tebartz van Elst
BACKGROUND: We previously described inflammatory cerebrospinal fluid (CSF) alterations in a subgroup of patients with schizophreniform disorders and the synthesis of polyspecific intrathecal antibodies against different neurotropic infectious pathogens in some patients with bipolar disorders. Consequently, we have measured the prevalence of a positive MRZ reaction (MRZR)-a marker for a polyspecific, antiviral, intrathecal, humoral immune response composed of three antibody indices for the neurotropic viruses of measles (M), rubella (R), and varicella zoster (Z)-in these patients...
December 7, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29183383/the-opioid-epidemic-a-central-role-for-the-blood-brain-barrier-in-opioid-analgesia-and-abuse
#18
REVIEW
Charles P Schaefer, Margaret E Tome, Thomas P Davis
Opioids are currently the primary treatment method used to manage both acute and chronic pain. In the past two to three decades, there has been a surge in the use, abuse and misuse of opioids. The mechanism by which opioids relieve pain and induce euphoria is dependent on the drug crossing the blood-brain barrier and accessing the central nervous system. This suggests the blood brain barrier plays a central role in both the benefits and risks of opioid use. The complex physiological responses to opioids that provide the benefits and drive the abuse also needs to be considered in the resolution of the opioid epidemic...
November 29, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29157263/ldl-receptor-blockade-reduces-mortality-in-a-mouse-model-of-ischaemic-stroke-without-improving-tissue-type-plasminogen-activator-induced-brain-haemorrhage-towards-pre-clinical-simulation-of-symptomatic-ich
#19
Be'eri Niego, Brad R S Broughton, Heidi Ho, Christopher G Sobey, Robert L Medcalf
BACKGROUND: Symptomatic intracerebral haemorrhage (sICH) following tissue-type plasminogen activator (rt-PA) administration is the most feared and lethal complication of thrombolytic therapy for ischaemic stroke, creating a significant obstacle for a broader uptake of this beneficial treatment. rt-PA also undermines cerebral vasculature stability in a multimodal process which involves engagement with LDL receptor-related protein 1 (LRP-1), potentially underlying the development of sICH...
November 21, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29110676/current-research-into-brain-barriers-and-the-delivery-of-therapeutics-for-neurological-diseases-a-report-on-cns-barrier-congress-london-uk-2017
#20
REVIEW
John Greenwood, Margareta Hammarlund-Udenaes, Hazel C Jones, Alan W Stitt, Roosmarijn E Vandenbrouke, Ignacio A Romero, Matthew Campbell, Gert Fricker, Birger Brodin, Heiko Manninga, Pieter J Gaillard, Markus Schwaninger, Carl Webster, Krzysztof B Wicher, Michel Khrestchatisky
This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers...
November 7, 2017: Fluids and Barriers of the CNS
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