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blood brain barrier permeability

Shuangwen Yu, Xiaolu Xu, Jianfang Feng, Mei Liu, Kaili Hu
Since the application of chitosan magnetic cationic microspheres in brain drug delivery by Gallo in 1993, chitosan has been extensively studied in brain drug delivery. As the only natural alkaline polysaccharide with good biocompatibility and biodegradability, chitosan prepared nanoparticles which use chitosan as carrier material to encapsulate drug have been proved with advantages of protecting from enzyme degradation, control release and improved bioavailability. Besides, chitosan can enhance drug permeability across the blood-brain barrier by affecting the tight junction...
February 14, 2019: International Journal of Pharmaceutics
Hongyan Liu, Xiaoming Qiang, Qing Song, Wei Li, Yuxi He, Chanyuan Ye, Zhenghuai Tan, Yong Deng
A series of 4'-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (65.03% at 25.0 μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro...
February 1, 2019: Bioorganic & Medicinal Chemistry
M Schön, Z Kovaničová, Z Košutzká, M Nemec, M Tomková, L Jacková, D Máderová, L Slobodová, P Valkovič, J Ukropec, B Ukropcová
Exercise can prevent the sedentary lifestyle-related risk of metabolic and cognitive decline, but mechanisms and mediators of exercise effects on human brain are relatively unexplored. We measured acute exercise-induced changes in adiponectin, insulin and other bioactive molecules in cerebrospinal fluid (CSF) and serum from young lean individuals. Samples of serum and CSF were obtained before and 1-h after the 90-min run (75-80% HRmax; maximal heart rate), additional serum was taken at finish-line. Body composition, physical fitness, metabolic rate, cognitive functions, food preference, glucose, insulin and albumin were measured...
February 13, 2019: Scientific Reports
Leif E Peterson
Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction...
February 12, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jin-Hui Yoon, Yong Jeong
Connections between various cell types in the brain enable cognitive function. The neurovascular unit is a structure composed of different cell types that regulate neurovascular coupling, blood-brain barrier permeability, and other interactions with peripheral systems. The relationship among the components of the neurovascular unit is complex and difficult to study without the use of in vivo neurovascular disease imaging. In this review, we introduce principles and examples of various in vivo optical imaging techniques including laser Doppler flowmetry, laser speckle contrast imaging, intrinsic optical signal imaging, optical coherence tomography, and two-photon microscopy...
February 11, 2019: Archives of Pharmacal Research
Yasushi Hattori, Kazunobu Aoyama, Jun Maeda, Naoto Arimura, Yasuko Takahashi, Masako Sasaki, Masayuki Fujinaga, Chie Seki, Yuji Nagai, Kazunori Kawamura, Tomoteru Yamasaki, Ming-Rong Zhang, Makoto Higuchi, Tatsuki Koike
Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL...
February 12, 2019: Journal of Medicinal Chemistry
Benjamin M Aertker, Akshita Kumar, Karthik S Prabhakara, Philippa Smith, Naama E Toledano Furman, Xue Hasen, Charles S Cox, Supinder S Bedi
Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (Mo /Ma ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating Mo /Ma , we utilized a monocyte/macrophage depletion model in response to TBI in male rats. Clodronate liposomes (CL) were used to deplete circulating Mo /Ma . A controlled cortical impact (CCI) injury model was used to create a TBI...
February 12, 2019: Journal of Neuroscience Research
Martin Krueger, Bianca Mages, Constance Hobusch, Dominik Michalski
In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO...
February 11, 2019: Acta Neuropathologica Communications
David Lagier, David Tonon, Philippe Garrigue, Benjamin Guillet, Laura Giacomino, Jean-Charles Martin, Marie-Christine Alessi, Nicolas Bruder, Lionel J Velly
BACKGROUND: Several lipid metabolites in cerebrospinal fluid are correlated with poor outcomes in aneurysmal subarachnoid haemorrhage. Most of these metabolites bind to ubiquitous thromboxane-prostaglandin (TP) receptors, causing vasoconstriction and inflammation. Here, we evaluated terutroban (TBN), a specific TP receptor antagonist, for the prevention of post-haemorrhage blood-brain barrier disruption, neuronal apoptosis and delayed cerebral hypoperfusion. METHODS: The rat double subarachnoid haemorrhage model was produced by twice injecting (days 1 and 2) autologous blood into the cisterna magna...
February 11, 2019: Critical Care: the Official Journal of the Critical Care Forum
Alexandra Bocsik, Ilona Gróf, Lóránd Kiss, Ferenc Ötvös, Ottó Zsíros, Lejla Daruka, Lívia Fülöp, Monika Vastag, Ágnes Kittel, Norbert Imre, Tamás A Martinek, Csaba Pál, Piroska Szabó-Révész, Mária A Deli
The absorption of drugs is limited by the epithelial barriers of the gastrointestinal tract. One of the strategies to improve drug delivery is the modulation of barrier function by the targeted opening of epithelial tight junctions. In our previous study the 18-mer amphiphilic PN159 peptide was found to be an effective tight junction modulator on intestinal epithelial and blood⁻brain barrier models. PN159, also known as KLAL or MAP, was described to interact with biological membranes as a cell-penetrating peptide...
February 10, 2019: Pharmaceutics
Takeo Yoshikawa, Tadaho Nakamura, Kazuhiko Yanai
Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N -methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood⁻brain barrier permeability have not been available until now...
February 10, 2019: International Journal of Molecular Sciences
Jian Ren, Chang-Liang Hu, Zheng-Ping Zhang, Rong Chen, Shi-Bao Yang, Zhen-Yu Miao, Lu-Ning Sun, Yong-Qing Wang
(+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard...
January 31, 2019: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Justin T Hsieh, Abhay P S Rathore, Gayathri Soundarajan, Ashley L St John
Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis. However, the mechanisms of JEV penetration of the blood-brain-barrier (BBB) remain poorly understood. Mast cells (MCs) are granulated innate immune sentinels located perivascularly, including at the BBB. Here we show that JEV activates MCs, leading to the release of granule-associated proteases in vivo. MC-deficient mice display reduced BBB permeability during JEV infection compared to congenic wild-type (WT) mice, indicating that enhanced vascular leakage in the brain during JEV infection is MC-dependent...
February 11, 2019: Nature Communications
Ran Li, Poornima Venkat, Michael Chopp, Qiang Zhang, Tao Yan, Jieli Chen
Subarachnoid hemorrhage (SAH) results in neurological damage, acute cardiac damage and has a high mortality rate. Immunoresponse in the acute phase after SAH plays a key role in mediating vasospasm, edema, inflammation and neuronal damage. The S1P/S1PR pathway impacts multiple cellular functions, exerts anti-inflammatory and anti-apoptotic effects, promotes remyelination, and improves outcome in several central nervous system (CNS) diseases. RP001 hydrochloride is a novel S1PR agonist, which sequesters lymphocytes within their secondary tissues and prevents infiltration of immune cells into the CNS thereby reducing immune response...
February 5, 2019: Journal of the Neurological Sciences
George W Farr, Christopher H Hall, Susan M Farr, Ramon Wade, Joshua M Detzel, Amielia G Adams, Jasen M Buch, Derek L Beahm, Christopher A Flask, Kui Xu, Joseph C LaManna, Paul R McGuirk, Walter F Boron, Marc F Pelletier
Cerebral edema in ischemic stroke can lead to increased intracranial pressure, reduced cerebral blood flow and neuronal death. Unfortunately, current therapies for cerebral edema are either ineffective or highly invasive. During the development of cytotoxic and subsequent ionic cerebral edema water enters the brain by moving across an intact blood brain barrier and through aquaporin-4 (AQP4) at astrocyte endfeet. Using AQP4-expressing cells, we screened small molecule libraries for inhibitors that reduce AQP4-mediated water permeability...
February 6, 2019: Neuroscience
Raoof Negaresh, Robert W Motl, Philipp Zimmer, Motahare Mokhtarzade, Julien S Baker
BACKGROUND: Multiple sclerosis is a demyelinating and neurodegenerative disease of the central nervous system that can be tracked through biomarkers of disease status. We investigated the effects of exercise on MS biomarkers associated with central nervous system status including imaging, blood-brain barrier function and neurotrophic factors. METHODS: We conducted open-dated searches of Scopus, Medline, EMBASE and the Cochrane Library. We included studies written in English describing interventions of exercise that measured one or more of the biomarkers associated with multiple sclerosis published until October 2018...
February 8, 2019: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
J Ivanidze, M Mackay, A Hoang, J M Chi, K Cheng, C Aranow, B Volpe, B Diamond, P C Sanelli
We report a prospective dynamic contrast-enhanced MR imaging analysis of region-specific blood-brain barrier permeability in 5 healthy subjects. By means of standardized postprocessing and ROI sampling methods, the hippocampi revealed significantly elevated area under the dynamic contrast-enhanced curve and significantly increased blood-brain barrier permeability metrics (volume transfer constant and volume in the extravascular extracellular space) from model-based quantitation. These findings suggest unique blood-brain barrier permeability characteristics in the hippocampus, which are concordant with previous animal studies, potentially laying the groundwork for future studies assessing patient populations in which hippocampal pathology plays a role...
February 7, 2019: AJNR. American Journal of Neuroradiology
Audrey P Fan, Ahmed A Khalil, Jochen B Fiebach, Greg Zaharchuk, Arno Villringer, Kersten Villringer, Claudine J Gauthier
Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients...
February 7, 2019: Journal of Cerebral Blood Flow and Metabolism
Alexandre Androuin, Yah-Se Abada, Myriam Ly, Mathieu Santin, Alexandra Petiet, Stéphane Epelbaum, Anne Bertrand, Benoît Delatour
Alzheimer's disease (AD) is the most common cause of dementia. Aside neuropathological lesions, abnormal neuronal activity and brain metabolism are part of the core symptoms of the disease. Activity-induced Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) has been proposed as a powerful approach to visualize evoked brain activity in rodents. Here, we evaluated the relevance of MEMRI in measuring neuronal (dys-)function in the APPxPS1 knocked-in (KI) mouse model of AD. Brain anomalies were firstly demonstrated in APPxPS1-Ki mice using cognitive testing (memory impairment) and histological mapping of immediate early gene products (decreased density of fos-positive neurons)...
February 4, 2019: Scientific Reports
Qing-Song Lin, Wei-Xiong Wang, Yuan-Xiang Lin, Zhang-Ya Lin, Liang-Hong Yu, Yin Kang, De-Zhi Kang
OBJECTIVEGlutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.METHODSEndovascular perforation was performed to induce SAH in male Sprague-Dawley rats...
February 1, 2019: Journal of Neurosurgery
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