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Blood-brain barrier

Athena E Theyers, Benjamin I Goldstein, Arron Ws Metcalfe, Andrew D Robertson, Bradley J MacIntosh
Arterial stiffness is linked to cerebral small vessel damage and neurodegeneration, but barriers to accessing deep cerebrovascular anatomy limit our ability to assess the brain. This study describes an adaptation of a cardiac-related scrubbing method as a means of generating blood oxygenation level-dependent pulsatility maps based on the cardiac cycle. We examine BOLD pulsatility at rest, based on the non-parametric deviation from null metric, as well as changes following acute physiological stress from 20 min of moderate-intensity cycling in 45 healthy adolescents...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Andrea E Toth, Piotr Siupka, Thomas J P Augustine, Susanne T Venø, Louiza B Thomsen, Torben Moos, Hannes T Lohi, Peder Madsen, Karin Lykke-Hartmann, Morten S Nielsen
Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes...
March 20, 2018: Molecular Neurobiology
Anjan Debnath, Andrew T Nelson, Angélica Silva-Olivares, Mineko Shibayama, Dionicio Siegel, James H McKerrow
Primary amebic meningoencephalitis (PAM) is a fatal infection caused by the free-living ameba Naegleria fowleri , popularly known as the "brain-eating ameba." The drugs of choice in treating PAM are the antifungal amphotericin B and an antileishmanial miltefosine, but these are not FDA-approved for this indication and use of amphotericin B is associated with severe adverse effects. Moreover, very few patients treated with the combination therapy have survived PAM. Therefore, development of efficient drugs is a critical unmet need to avert future deaths of children...
2018: Frontiers in Microbiology
Li Liu, Mingxing Miao, Yang Chen, Zhongjian Wang, Binbin Sun, Xiaodong Liu
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl- S -glutathione, respectively...
2018: Frontiers in Pharmacology
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
Antonio Lopalco, Annalisa Cutrignelli, Nunzio Denora, Angela Lopedota, Massimo Franco, Valentino Laquintana
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl- sn -glycero-3-phosphoethanolamine- N -[carboxy(poly(ethylene glycol)-2000)]...
March 20, 2018: Nanomaterials
Mathias Kranz, Ralf Bergmann, Torsten Kniess, Birgit Belter, Christin Neuber, Zhengxin Cai, Gang Deng, Steffen Fischer, Jiangbing Zhou, Yiyun Huang, Peter Brust, Winnie Deuther-Conrad, Jens Pietzsch
Sigma-1 receptors (Sig1R) are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET) can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers ( S )-(-)- and ( R )-(+)-[18 F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging...
March 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Naif E Al Omairi, Omyma K Radwan, Yahea A Alzahrani, Rami B Kassab
Due to the high ability of cadmium to cross the blood-brain barrier, cadmium (Cd) causes severe neurological damages. Hence, the purpose of this study was to investigate the possible protective effect of Mangifera indica leaf extract (MLE) against Cd-induced neurotoxicity. Rats were divided into eight groups. Group 1 served as vehicle control group, groups 2, 3 and 4 received MLE (100, 200, 300 mg /kg b.wt, respectively). Group 5 was treated with CdCl2 (5 mg/kg b.wt). Groups 6, 7 and 8 were co-treated with MLE and CdCl2 using the same doses...
March 20, 2018: Metabolic Brain Disease
Robert Galinsky, Joanne O Davidson, Justin M Dean, Colin R Green, Laura Bennet, Alistair J Gunn
Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypothermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction (connexin) hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation...
February 2018: Neural Regeneration Research
Kathryn F Kirchoff-Torres, Ekaterina Bakradze
PURPOSE OF REVIEW: Cerebral hyperperfusion syndrome (CHS) is a rare but significant complication after carotid revascularization and is increasingly recognized after acute stroke treatments. In this review, we discuss the epidemiology and pathophysiology of CHS, clinical presentation including ipsilateral headache, seizures, and focal neurological deficits, and radiographic presentation. We propose preventive therapies with emphasis on acute stroke post-thrombectomy hyperperfusion. RECENT FINDINGS: CHS was first described after carotid revascularization but is now also reported in patients with acute ischemic stroke...
March 19, 2018: Current Pain and Headache Reports
Xiaowei Dong
The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years...
2018: Theranostics
Hongchen Hua, Xuemei Zhang, Hongjie Mu, Qingqing Meng, Ying Jiang, Yiyun Wang, Xiaoyan Lu, Aiping Wang, Sha Liu, Yaping Zhang, Zhihui Wan, Kaoxiang Sun
Gliomas are the most common malignant brain tumor, but treatment is limited by the blood-brain barrier (BBB), especially for chemotherapeutic drugs. Although some chemotherapy drugs can pass through the BBB, many of these agents are toxic to normal brain tissue. To maximize therapeutic effects, chemotherapeutic drugs must accumulate at the glioma site. In this study, a specific ligand (the RVG29 peptide) that can combine with acetylcholine receptors was conjugated to polyethylene glycol-modified poly-(D,L-lactide-co-glycolide) (PEG-PLGA) to develop a targeted carrier; preparation of the targeted docetaxel nanoparticles (DTX-NPs) was performed by the nanoprecipitation method...
March 16, 2018: International Journal of Pharmaceutics
Norma Oviedo, Leticia Manuel-Apolinar, Sandra Orozco-Suárez, Teresa Juárez-Cedillo, Vilma Carolina Bekker Méndez, Emiliano Tesoro-Cruz
BACKGROUND: Intranasal administration (Int adm) has been well-studied and offers the possibility to deliver larger molecular weight biologics, such as proteins, viral vectors, nanoparticles, and naked plasmids to the brain and treat a variety of diseases in the central nervous system. The predominant challenge in this field is finding efficient vectors that are capable of crossing the blood-brain barrier (BBB). OBJECTIVES: Here, we investigated whether a naked plasmid (pIRES-hrGFP-1a), could cross the BBB, reach brain cells and express green fluorescent protein (GFP) after int-adm and propose it as candidate for future gene therapy studies...
March 16, 2018: Archives of Medical Research
Alexandra M Durrant, Matthew N Swift, Nicholas Beazley-Long
PURPOSE OF REVIEW: The importance of the blood-brain barrier (BBB) and neuroinflammation in neurodegenerative conditions is becoming increasingly apparent, yet very little is known about these neurovascular functions in nonmalignant disease chronic pain. Neural tissue pericytes play critical roles in the formation and maintenance of the BBB. Herein, we review the important roles of neural pericytes and address their potential role in chronic pain. RECENT FINDINGS: Pericytes are implicated in the function of neural microvasculature, including BBB permeability, neuroimmune factor secretion and leukocyte transmigration...
March 16, 2018: Current Opinion in Supportive and Palliative Care
Kavi Devraj, Sylvaine Guérit, Jakranka Macas, Yvonne Reiss
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function...
February 26, 2018: Journal of Visualized Experiments: JoVE
Meng-Tsan Tsai, Jia-Wei Zhang, Kuo-Chen Wei, Chih-Kuang Yeh, Hao-Li Liu
Focused ultrasound (FUS) in combination with microbubbles temporally and locally increases the permeability of the blood-brain barrier (BBB) for facilitating drug delivery. However, the temporary effects of FUS on the brain microstructure and microcirculation need to be addressed. We used label-free optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the morphological and microcirculation changes in mouse brains due to FUS exposure at different power levels. Additionally, the recovery progress of the induced effects was studied...
February 1, 2018: Biomedical Optics Express
Chie-Hong Wang, Tsung-Li Lin, Chih-Hsin Muo, Chen-Huan Lin, Yu-Chuen Huang, Ru-Huei Fu, Woei-Cherng Shyu, Shih-Ping Liu
Background and purpose: The blood-brain barrier (BBB) not only provides a physical obstruction but also recruits and activates neutrophils in cases of infection. Hemorrhagic or ischemic stroke reportedly induces the disruption of the BBB. However, few studies have reported a correlation between the incidence of meningitis in patients with a history of stroke. This study tested the hypothesis that patients with a history of stroke may be more vulnerable to meningitis. Methods: Stroke and age-matched comparison ( n  = 29,436 and 87,951, respectively) cohorts were recruited from the Taiwan National Health Insurance database (2000-2011)...
2018: Frontiers in Neurology
Sara Milanizadeh, Karrar Najm Najaf Zuwarali, Abbas Aliaghaei, Mohammad Reza Bigdeli
Brain ischemia is one of the most common causes of death and disability worldwide, which usually happens through diminished blood supply to the tissue. Cell therapy and treatments using trophic factors are some of the new methods to protect brain cells against damage. Specific properties of Sertoli cells (SCs) make them suitable for improving neurological disorders. This study is to evaluate possible neuroprotective effects of SCs transplantation on ischemic damage. Rats were divided into three experimental groups including sham, control, and SCs-treated group...
March 17, 2018: Journal of Molecular Neuroscience: MN
Chen Fu, Yonggang Xiang, Xiaorong Li, Ailing Fu
For successful theranosis of brain diseases, limited access of therapeutic molecules across blood-brain barrier (BBB) needs be overcome in brain delivery. Currently, peptide derivatives of rabies virus glycoprotein (RVG) have been exploited as delivery ligands to transport nanocarriers across BBB and specifically into the brain. The targeting peptides usually conjugate to the nanocarrier surface, and the cargoes, including siRNA, miRNA, DNA, proteins and small molecular chemicals, are complexed or encapsulated in the nanocarriers...
June 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Cindy R Timme, Barbara H Rath, John W O'Neill, Kevin Camphausen, Philip J Tofilon
Radiotherapy is a primary treatment modality for glioblastomas (GBMs). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSBs), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation...
March 16, 2018: Molecular Cancer Therapeutics
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