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Blood brain barrier

Mohammad A Kaisar, Ravi K Sajja, Shikha Prasad, Vinay V Abhyankar, Taylor Liles, Luca Cucullo
The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered: This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies...
October 26, 2016: Expert Opinion on Drug Discovery
Ximin Zhu, Yongliang Cao, Lixiang Wei, Ping Cai, Haochen Xu, Haiyu Luo, Xiaofei Bai, Lu Lu, Jian-Ren Liu, Wenying Fan, Bing-Qiao Zhao
Spontaneous intracerebral haemorrhage (ICH) is the most devastating stroke subtype and has no proven treatment. von Willebrand factor (VWF) has recently been demonstrated to promote inflammation processes. The present study investigated the pathophysiological role of VWF after experimental ICH. Functional outcomes, brain edema, blood-brain barrier (BBB) permeability, cerebral inflammation and levels of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in a mouse model of ICH induced by autologous blood injection...
October 26, 2016: Scientific Reports
Young Bin Ji, Seung Jae Oh, Seok-Gu Kang, Jung Heo, Sang-Hoon Kim, Yuna Choi, Seungri Song, Hye Young Son, Se Hoon Kim, Ji Hyun Lee, Seung Joo Haam, Yong Min Huh, Jong Hee Chang, Chulmin Joo, Jin-Suck Suh
Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas...
October 26, 2016: Scientific Reports
Alec Hughes, Yuexi Huang, Aki Pulkkinen, Michael L Schwartz, Andres M Lozano, Kullervo Hynynen
Recent clinical data showing thermal lesions from treatments of essential tremor using MR-guided transcranial focused ultrasound shows that in many cases the focus is oblique to the main axis of the phased array. The potential for this obliquity to extend the focus into lateral regions of the brain has led to speculation as to the cause of the oblique focus, and whether it is possible to realign the focus. Numerical simulations were performed on clinical export data to analyze the causes of the oblique focus and determine methods for its correction...
November 21, 2016: Physics in Medicine and Biology
Lutz Menzel, Lisa Kleber, Carina Friedrich, Regina Hummel, Larissa Dangel, Jennifer Winter, Katja Schmitz, Irmgard Tegeder, Michael K E Schäfer
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn(-/-) ) 24 h and 5 days after experimental TBI...
October 25, 2016: Glia
Jenni Kyyriäinen, Xavier Ekolle Ndode-Ekane, Asla Pitkänen
Platelet-derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood-brain barrier (BBB) damage. We investigated the time-window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid-induced status epilepticus (SE) and in rats with lateral fluid-percussion-induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time-points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type-specific expression was verified with double/triple-labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA-1)...
October 25, 2016: Glia
Consuelo J Perez, Alessandra Tata, Michel L de Campos, Chun Peng, Demian R Ifa
Ambient mass spectrometry imaging has become an increasingly powerful technique for the direct analysis of biological tissues in the open environment with minimal sample preparation and fast analysis times. In this study, we introduce desorption electrospray ionization mass spectrometry imaging (DESI-MSI) as a novel, rapid, and sensitive approach to localize the accumulation of a mildly toxic ionic liquid (IL), AMMOENG 130 in zebrafish (Danio rerio). The work demonstrates that DESI-MSI has the potential to rapidly monitor the accumulation of IL pollutants in aquatic organisms...
October 24, 2016: Journal of the American Society for Mass Spectrometry
Jacinta Nwamaka Nwogu, Qing Ma, Chinedum Peace Babalola, Waheed Adeola Adedeji, Gene D Morse, Babafemi Taiwo
Neurological complications associated with the human immunodeficiency virus (HIV) are a matter of great concern. While antiretroviral (ARV) drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow...
2016: AIDS Research and Treatment
Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
Ma Ke, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial for myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis (MS). Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
October 23, 2016: Journal of Neurochemistry
Min-Wang Zhang, She-Feng Zhang, Zhen-Hua Li, Fang Han
7,8-Dihydroxyflavone (7,8-DHF) is a naturally-occurring flavone which possesses good bioavailability. Due to its ability to cross the blood-brain barrier, previous studies have demonstrated that 7,8-DHF was a potent tropomyosin-related kinase B (TrkB) agonist, and produced antidepressant-like effects in mouse forced swimming test and tail suspension test. However, it has not been evaluated in chronic mild stress (CMS), a classical depression model modulating the processes of major depression in human. In the present study, we not only evaluated the depressive-like behaviors, but also measured the key proteins of TrkB signaling in mice exposed to CMS...
October 20, 2016: Neuroscience Letters
Ibiayi Dagogo-Jack, Corey M Gill, Daniel P Cahill, Sandro Santagata, Priscilla K Brastianos
Development of brain metastasis (BM) portends a dismal prognosis for patients with cancer. Melanomas and carcinomas of the lung, breast, and kidney are the most common malignancies to metastasize to the brain. Recent advances in molecular genetics have enabled the identification of actionable, clinically relevant genetic alterations within primary tumors and their corresponding metastases. Adoption of genotype-guided treatment strategies in the management of systemic malignancy has resulted in dramatic and durable responses...
October 20, 2016: Pharmacology & Therapeutics
Marcos Guilherme da Cunha, Gilson César Nobre Franco, Marcelo Franchin, John A Beutler, Severino Matias de Alencar, Masaharu Ikegaki, Pedro Luiz Rosalen
In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array...
October 20, 2016: Toxicology Letters
Ming-Liang Wang, Wen-Bin Li
Traumatic brain injury (TBI) is closely related to increased incidence of cognitive impairment from the acute phase to chronic phase. At present, the pathological mechanism leading to cognitive impairment after TBI is still not fully understood. We hypothesize that neuron loss, diffuse axonal injury, microbleed, and blood-brain barrier (BBB) disruption altogether contribute to the development of cognitive impairment. Furthermore, the disruption of structural and functional neural network related to the cognitive function might bring about the final step in the occurrence of cognitive impairment after TBI...
November 15, 2016: Journal of the Neurological Sciences
Danyang Wang, Lin-Ping Wu
Billions of dollars have been invested in the therapeutic application of nucleic acid-based agents in humans in recent years. There are inspirable data from ongoing clinical trial for different diseases. However, in order to widely apply nucleic acid in prevention, diagnosis and treatment of age-related disease, such as neurodegeneration and disorders, suitable, safe and effective drug delivery nanocarriers have to been developed to overcome the blood brain barrier (BBB), which is the most inflexible barrier in human body...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Geun Hee Seol, Ka Young Kim
Patients with chronic diseases such as cardiovascular diseases, chronic respiratory diseases, and neurological diseases have been shown to benefit from treatments such as aromatherapy in addition to medication. Most chronic diseases are caused by chronic inflammation and oxidative stress as well as harmful factors. Eucalyptol (1,8-cineole), a terpenoid oxide isolated from Eucalyptus species, is a promising compound for treating such conditions as it has been shown to have anti-inflammatory and antioxidant effects in various diseases, including respiratory disease, pancreatitis, colon damage, and cardiovascular and neurodegenerative diseases...
2016: Advances in Experimental Medicine and Biology
Ye Chen, Yu Lei, Li-Qun Mo, Jun Li, Mao-Hua Wang, Ji-Cheng Wei, Jun Zhou
Sepsis is associated with high morbidity and mortality. This study was to investigate the protective effects of electroacupuncture (EA) pretreatment with different waveforms on septic brain injury in rats and its mechanism. Male Sprague-Dawley rats were pretreated by EA with different waveforms (continuous wave, dilatational wave, or intermittent wave) at Baihui (GV20) and Tsusanli (ST36) acupoints for 30min, and underwent cecal ligation and puncture (CLP) or sham operation. The results showed that EA pretreatment with different waveforms improved survival rate, attenuated encephaledema, brain injury, neuronal apoptosis and cognitive dysfunction, and preserved blood-brain barrier(BBB)...
October 19, 2016: Brain Research Bulletin
Manjit Kaur, Raj K S Badhan
Clinical translation of BCRP inhibitors have failed due to neurotoxicity and novel approaches are required to identify suitable modulators of BCRP to enhance CNS drug delivery. In this study we examine 18 compounds, primarily phytochemicals, as potential novel modulators of AhR-mediated regulation of BCRP expression and function in immortalised and primary porcine brain microvascular endothelial cells as a mechanism to enhance CNS drug delivery. The majority of modulators possessed a cellular viability IC50 > 100µM in both cell systems...
October 19, 2016: Brain Research
Gabor Nagy, Viktoria Baksa, Alexandra Kiss, Melinda Turani, Gaspar Banfalvi
The toxicity of gadolinium is reduced by chelating agents that render this heavy metal into contrast complexes used for medical magnetic resonance imaging. However, the dissociation of gadolinium chelates is known to generate Gd(3+) ions, the cellular toxicity of which has not been tested in details. The cytotoxic effects of Gd(III) ions were evaluated by monitoring the proliferation, measuring the cellular motility and following chromatin changes in various cell lines upon Gd(3+) treatment. Measurements applied long-term scanning microscopy and a perfusion platform that replaced the medium with test solutions, bypassed physical contact with the cell culture during experiments, and provided uninterrupted high time-resolution time-lapse photomicrography for an extended period of time...
October 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
Maria Gregori, Mark Taylor, Elisa Salvati, Francesca Re, Simona Mancini, Claudia Balducci, Gianluigi Forloni, Vanessa Zambelli, Silvia Sesana, Maria Michael, Christos Michail, Claire Tinker-Mill, Oleg Kolosov, Michael Scherer, Stephen Harris, Nigel J Fullwood, Massimo Masserini, David Allsop
Aggregation of Amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
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