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https://www.readbyqxmd.com/read/29031222/apolipoproteins-adsorption-and-brain-targeting-evaluation-of-baicalin-nanocrystals-modified-by-combination-of-tween80-and-tpgs
#1
Yang Liu, Yueqin Ma, Junnan Xu, Yingchong Chen, Jin Xie, Pengfei Yue, Qin Zheng, Ming Yang
To help baicalin pass across BBB and improve its targeting in brain, we designed a novel formulation strategy of baicalin nanocrystals that preferentially adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins. Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different surfactant were prepared by high-pressure homogenization. The targeting potential of surface-modified BCL-NS with mean particles size of about 250nm was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics...
October 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29028768/hydrogen-gas-treatment-improves-the-neurological-outcome-after-traumatic-brain-injury-via-increasing-mir-21-expression
#2
Lu Wang, Chongfa Zhao, Shuang Wu, Guanghui Xiao, Xin Zhuge, Ping Lei, Keliang Xie
Hydrogen gas (H2) exerts a beneficial effect against traumatic brain injury (TBI). miR-21 is one of the most highly expressed members of small non-coding microRNA family in mammalian cells. miR-21 can improve the neurological outcome after TBI. In the present study, we investigated whether H2 treatment could improve the neurological outcome after TBI via increasing miR-21 expression. TBI was induced by controlled cortical impact (CCI) in rats. H2 treatment was given by exposure to 2% H2 from 30 minutes to 5 hours after TBI operation...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/29028747/nervous-system-delivery-of-antilysophosphatidic-acid-antibody-by-nasal-application-attenuates-mechanical-allodynia-after-traumatic-brain-injury-in-rats
#3
Andreas Eisenried, Anders C N Meidahl, Michael Klukinov, Alexander Z Tzabazis, Roger A Sabbadini, J David Clark, David C Yeomans
Lysophosphatidic acid (LPA) is a bioactive lipid that impacts neurological outcomes after neurotrauma by inhibiting neuroregeneration, promoting inflammation, and contributing to behavioral deficits. Blocking LPA signaling with a novel anti-LPA monoclonal antibody (mAb) is neuroprotective after traumatic brain injury (TBI) if given to injured animals whose blood-brain barrier (BBB) has been compromised. It is hypothesized that the anti-LPA mAb could improve chronic pain initiated by TBI. However, poor brain penetration after systemic application of the antibody makes access to the central nervous system (CNS) problematic in situations where the BBB is intact...
November 2017: Pain
https://www.readbyqxmd.com/read/29028353/activated-microglia-targeting-dendrimer-minocycline-conjugate-as-therapeutics-for-neuroinflammation
#4
Rishi Sharma, Soo-Young Kim, Anjali Sharma, Zhi Zhang, Siva Pramodh Kambhampati, Sujatha Kannan, Rangaramanujam M Kannan
Brain related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood brain barrier (BBB), and potency. Despite its potential in the clinic, and in preclinical models, the high doses needed to affect a positive therapeutic response has led to side effects...
October 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#5
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29025771/endothelial-activation-and-blood-brain-barrier-disruption-in-neurotoxicity-after-adoptive-immunotherapy-with-cd19-car-t-cells
#6
Juliane Gust, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, David Myerson, Luis F Gonzalez-Cuyar, Cecilia Yeung, W Conrad Liles, Mark Wurfel, Jose A Lopez, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Tahsin Özpolat, Kathleen R Fink, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19(+) cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability...
October 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29023711/alteration-of-sphingolipid-metabolism-as-a-putative-mechanism-underlying-lps-induced-bbb-disruption
#7
Rajkumar Vutukuri, Robert Brunkhorst, Roxane-Isabelle Kestner, Lena Hansen, Nerea Ferreiros Bouzas, Josef Pfeilschifter, Kavi Devraj, Waltraud Pfeilschifter
Septic encephalopathy with confusion and agitation occurs early during sepsis and contributes to the severity of the disease. A decrease of the sphingosine-1-phosphate (S1P) blood levels has been shown in patients and in animal models of sepsis. The lipid mediator S1P is known to be involved in endothelial barrier function in a context-dependent manner. We utilized LPS injected mice as a model for septic encephalopathy and first performed tracer permeability assays to assess the BBB breakdown in vivo. At time points corresponding to the BBB breakdown post LPS injection, we aimed to characterize the regulation of the sphingolipid signaling pathway at the blood-brain barrier (BBB) during sepsis...
October 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29022894/adiponectin-controls-the-apoptosis-and-the-expression-of-tight-junction-proteins-in-brain-endothelial-cells-through-adipor1-under-beta-amyloid-toxicity
#8
Juhyun Song, Seong-Min Choi, Daniel J Whitcomb, Byeong C Kim
Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by excessive beta amyloid (Aβ) deposition in brain, leading to blood-brain barrier (BBB) disruption. The mechanisms of BBB disruption in AD are still unclear, despite considerable research. The adipokine adiponectin is known to regulate various metabolic functions and reduce inflammation. Though adiponectin receptors have been reported in the brain, its role in the central nervous system has not been fully characterized. In the present study, we investigate whether adiponectin contributes to the tight junction integrity and cell death of brain endothelial cells under Aβ-induced toxicity conditions...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29020807/recognizing-the-role-of-cgrp-and-cgrp-receptors-in-migraine-and-its-treatment
#9
Lars Edvinsson, Karin Warfvinge
Premise The brain and the sensory nervous system contain a rich supply of calcitonin gene-related peptide (CGRP) and CGRP receptor components. Clinical studies have demonstrated a correlation between CGRP release and acute migraine headache that led to the development of CGRP-specific drugs that either abort acute attacks of migraine (gepants) or are effective as prophylaxis (antibodies). However, there is still much discussion concerning the site of action of these drugs. Problem Here we describe the most recent data related to CGRP in the trigeminal ganglion and its connections to the CNS, putative key regions involved in migraine pathophysiology...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29018647/burden-of-arrhythmias-in-epilepsy-patients-a-nationwide-inpatient-analysis-of-1-4-million-hospitalizations-in-the-united-states
#10
Rupak Desai, Chintan Rupareliya, Upenkumar Patel, Syeda Naqvi, Smit Patel, Abhishek Lunagariya, Zabeen Mahuwala
Arrhythmias have been one of the common complications in epilepsy patients and have also been the reason for death. However, limited data exist about the burden and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating the burden and differences in outcomes of various subtypes of arrhythmias in epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from 2014 was examined for epilepsy and arrhythmias related discharges using appropriate International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes...
August 8, 2017: Curēus
https://www.readbyqxmd.com/read/29017981/prolonged-intracisternal-papaverine-toxicity-index-case-description-and-proposed-mechanism-of-action
#11
REVIEW
Xiaofei Zhou, Vilakshan Alambyan, Thomas Ostergard, Jonathan Pace, Maryo Kohen, Sunil Manjila, Ciro Ramos-Estebanez
Intracisternal papaverine (iPPV) is a vasodilator used for prophylaxis of intra-operative vasospasm during aneurysmal clipping. Its post-operative side effects include transient cranial nerve palsies, most commonly mydriasis due to oculomotor nerve involvement with rapid resolution. We critically review the current literature on the adverse effects of iPPV in aneurysmal surgery, with a focus on oculomotor nerve involvement. In addition, this manuscript portrays the index case of prolonged bilateral mydriasis secondary to iPPV irrigation toxicity and its putative underlying mechanism...
October 7, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29016900/is-the-blood-brain-barrier-really-disrupted-in-all-glioblastomas-a-critical-assessment-of-existing-clinical-data
#12
Jann N Sarkaria, Leland S Hu, Ian F Parney, Deanna H Pafundi, Debra H Brinkmann, Nadia N Laack, Caterina Giannini, Terence C Burns, Sani H Kizilbash, Janice K Laramy, Kristin R Swanson, Timothy J Kaufmann, Paul D Brown, Nathalie Y R Agar, Evanthia Galanis, Jan C Buckner, William F Elmquist
The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM...
September 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28994773/improved-method-for-the-establishment-of-an-in-vitro-blood-brain-barrier-model-based-on-porcine-brain-endothelial-cells
#13
Simone S E Nielsen, Piotr Siupka, Ana Georgian, Jane E Preston, Andrea E Tóth, Siti R Yusof, N Joan Abbott, Morten S Nielsen
The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation...
September 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28994715/%C3%AE-amyloid-and-the-pathomechanisms-of-alzheimer-s-disease-a-comprehensive-view
#14
REVIEW
Botond Penke, Ferenc Bogár, Lívia Fülöp
Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer's disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP). Enzymatic processing of APP may result in formation of toxic Aβ aggregates (β-amyloids). Protein folding is the basis of life and death. Intracellular Aβ affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca(2+)-dysregulation and lipid dyshomeostasis...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28994331/evaluating-the-involvement-of-cerebral-microvascular-endothelial-na-k-atpase-and-na-k-2cl-co-transporter-in-electrolyte-fluxes-in-an-in%C3%A2-vitro-blood-brain-barrier-model-of-dehydration
#15
Kasper Lykke, Mette Assentoft, Sofie Hørlyck, Hans Cc Helms, Anca Stoica, Trine L Toft-Bertelsen, Katerina Tritsaris, Frederik Vilhardt, Birger Brodin, Nanna MacAulay
The blood-brain barrier (BBB) is involved in brain water and salt homeostasis. Blood osmolarity increases during dehydration and water is osmotically extracted from the brain. The loss of water is less than expected from pure osmotic forces, due to brain electrolyte accumulation. Although the underlying molecular mechanisms are unresolved, the current model suggests the luminally expressed Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) as a key component, while the role of the Na(+)/K(+)-ATPase remains uninvestigated...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28993949/poly-n-methylated-a%C3%AE-peptide-c-terminal-fragments-meptides-reverse-the-deleterious-effects-of-amyloid-%C3%AE-in-rats
#16
Siya G Sibiya, Musa V Mbandla, Thavi Govender, Adeola Shobo, William M U Daniels
Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear...
October 9, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28993773/targeting-malignant-brain-tumors-with-antibodies
#17
REVIEW
Rok Razpotnik, Neža Novak, Vladka Čurin Šerbec, Uros Rajcevic
Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell-based approaches...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28993728/age-drives-distortion-of-brain-metabolic-vascular-and-cognitive-functions-and-the-gut-microbiome
#18
Jared D Hoffman, Ishita Parikh, Stefan J Green, George Chlipala, Robert P Mohney, Mignon Keaton, Bjoern Bauer, Anika M S Hartz, Ai-Ling Lin
Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#19
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28993322/comparative-study-of-expression-and-activity-of-glucose-transporters-between-stem-cell-derived-brain-microvascular-endothelial-cells-and-hcmec-d3-cells
#20
Abraham J Al-Ahmad
Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs)...
October 1, 2017: American Journal of Physiology. Cell Physiology
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