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Blood-brain barrier

Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
K Rygiel
Alzheimer's disease (AD) is a neurodegenerative disease, in which an accumulation of toxic amyloid beta in the brain precedes the emergence of clinical symptoms. AD spectrum consists of presymptomatic, early symptomatic, and symptomatic phase of dementia. At present, no pharmacotherapy exists to modify or reverse a course of AD, and only symptomatic treatments are available. Many elderly patients, diagnosed with multiple medical conditions (such as cardiovascular diseases, Type 2 diabetes mellitus, and cerebrovascular diseases) are at increased risk of the development of mild cognitive impairment (MCI), AD, and vascular dementia...
October 2016: Journal of Postgraduate Medicine
Guy Bar-Klein, Rebecca Klee, Claudia Brandt, Marion Bankstahl, Pablo Bascuñana, Kathrin Töllner, Hotjensa Dalipaj, Jens P Bankstahl, Alon Friedman, Wolfgang Löscher
OBJECTIVE: Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Due to the complex alterations involved in epileptogenesis, it is likely that multi-targeted approaches are required for epilepsy prevention. We report novel preclinical findings with isoflurane, which exerts various non-anesthetic effects that may be relevant for anti-epileptogenesis...
October 19, 2016: Annals of Neurology
Yanhan Liu, Pan Hao, Xiao Zhang, Xiaona Zhao, Yongxia Liu, Jianzhu Liu
This study aimed to investigate the effects of chromic chloride (CrCl3) on Ca, Mg, Mn, Fe, Cu, and Zn contents in the brain and serum of chicken. Seventy-two chickens were randomly divided into four groups and treated with different doses of CrCl3 via drinking water: 0, 1/8, 1/4, and 1/2 LD50 for 42 days. The contents of the elements were evaluated through inductively coupled plasma mass spectrometry. Results showed that Cr contents in the brain and serum were higher than those in the control groups, although no significant dose-dependent changes (P > 0...
October 19, 2016: Biological Trace Element Research
S Kemp, R S Allan, N Patanjali, M H Barnett, B P Jonker
We report a unique case of neurological deficit from late onset multiple sclerosis (MS), in a 65-year-old woman, after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). At 3.5months post-SRS for TN, the patient developed ataxia and left leg paraesthesiae and brain MRI showed altered signal and enhancement in the vicinity of the right trigeminal root entry zone (REZ). The symptoms remitted following treatment with intravenous methylprednisolone, however, 10months post-SRS, the patient developed gait ataxia and left lower limb weakness...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Kamal Niaz, Mohammad Abdollahi
Zika virus (ZIKV) is a deadly flavivirus that has spread from Africa to Asia and European countries. The virus is associated with other viruses in the same genus or family, transmitted by the same mosquito species with known history of fatality. A sudden increase in the rate of infection from ZIKV has made it a global health concern, which necessitates close symptom monitoring, enhancing treatment options, and vaccine production. This paper reviewed current reports on birth defects associated with ZIKV, mode of transmission, body fluids containing the virus, diagnosis , possible preventive measures or treatments, and vaccine development...
October 18, 2016: Infectious Disorders Drug Targets
Cletus Cheyuo, Walter Grand, Lucia L Balos
BACKGROUND: Cytoarchitectural neuroimaging remains critical for diagnosis of many brain diseases. Fluorescent dye-enhanced, near-infrared confocal in situ cellular imaging of the brain has been reported. However, impermeability of the blood-brain barrier to most fluorescent dyes limits clinical utility of this modality. The differential degree of reflectance from brain tissue with unenhanced near-infrared imaging may represent an alternative technique for in situ cytoarchitectural neuroimaging...
October 15, 2016: World Neurosurgery
X Liu, X Zhang, K Ma, R Zhang, P Hou, B Sun, S Yuan, Z Wang, Z Liu
Matrine is a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescentis, and possesses anti-oxidant, anti-inflammatory and anti-tumoral properties. However, its effectiveness against subarachnoid hemorrhage (SAH) is not well known. In this study, we investigated the effects of matrine on early brain injury (EBI) and the related potential mechanisms following SAH in rats. Our results showed that matrine pretreatment partially alleviated SAH-induced EBI, including neurological deficit, severity of SAH grade, brain edema, and blood-brain barrier (BBB) disruption in rats...
September 30, 2016: Cellular and Molecular Biology
Laura Julia Starost, Sascha Karassek, Yasuteru Sano, Takashi Kanda, Kwang Sik Kim, Ulrich Dobrindt, Christian Rüter, Marcus Alexander Schmidt
Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood-brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E...
October 13, 2016: Toxins
Sverre Kjeldsen
There is a whole armament of good drugs for treatment of hypertension including diuretics, calcium antagonist, angiotensin receptor antagonists and angiotensin converting enzyme inhibitors. Secondary drugs mostly used for special indications include beta-blockers, alpha-blockers, mineralocorticoid receptor antagonists (aldosterone antagonists), renin-inhibitors, centrally acting drugs, direct vasodilators and others.A variety of new drugs targeting different pressor mechanism exist and have partly been studies experimentally but will unlikely make it to clinical use in human hypertension...
September 2016: Journal of Hypertension
João Casaca-Carreira, Yasin Temel, Iñaki Larrakoetxea, Ali Jahanshahi
Antisense oligonucleotide (AON) therapy is emerging as a potential treatment strategy for neurodegenerative diseases, such as spinal muscular atrophy, Huntington's disease, and amyotrophic lateral sclerosis. AONs function at the cellular level by, for example, direct interference with the expression of gene products or the molecular activation of neuroprotective pathways. However, AON therapy faces a major obstacle limiting its clinical application for central nervous system (CNS) disorders: the blood-brain barrier...
October 18, 2016: Nucleic Acid Therapeutics
M Asunción Barreda-Manso, Natalia Yanguas-Casás, Manuel Nieto-Sampedro, Lorenzo Romero-Ramírez
Following a central nervous system (CNS) injury, restoration of the blood-brain barrier (BBB) integrity is essential for recovering homeostasis. When this process is delayed or impeded, blood substances and cells enter the CNS parenchyma, initiating an additional inflammatory process that extends the initial injury and causes so-called secondary neuronal loss. Astrocytes and profibrotic mesenchymal cells react to the injury and migrate to the lesion site, creating a new glia limitans that restores the BBB. This process is beneficial for the resolution of the inflammation, neuronal survival and the initiation of the healing process...
October 18, 2016: Journal of Cellular Physiology
Hanne Kuitunen, Susanna Tokola, Topi Siniluoto, Matti Isokangas, Eila Sonkajärvi, Seppo Alahuhta, Taina Turpeenniemi-Hujanen, Esa Jantunen, Tapio Nousiainen, Kaija Vasala, Outi Kuittinen
Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation...
October 17, 2016: Journal of Neuro-oncology
Hidehito Kimura, Masaaki Taniguchi, Tatsuya Mori, Kohkichi Hosoda, Eiji Kohmura
We present a rare case of a patient suffering temporary aphasia after an extracranial-to-intracranial (EC-IC) bypass surgery, which was shown as a transient hypointense lesion on diffusion-weighted imaging (DWI) with increased apparent diffusion coefficient (ADC) value, evidence of postoperative hyperperfusion. Postoperative hyperperfusion syndrome after EC-IC bypass causing temporary neurological deterioration has been reported rarely as isosignal intensity on DWI with hyperintense lesion on T2-weighted image and fluid-attenuated inversion recovery (FLAIR) image as an expression of vasogenic edema...
October 14, 2016: World Neurosurgery
Raphaela Mayerhofer, Esther E Fröhlich, Florian Reichmann, Aitak Farzi, Nora Kogelnik, Eleonore Fröhlich, Wolfgang Sattler, Peter Holzer
Microbial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior...
October 14, 2016: Brain, Behavior, and Immunity
Sufyan Ahmad, Fatima Iftikhar, Farhat Ullah, Abdul Sadiq, Umer Rashid
Based on the pharmacological importance of dihydropyrimidine (DHPM) scaffold, substituted DHPMs linked with acetamide linker to substituted aromatic anilines were synthesized and evaluated for their potency as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The good AChE inhibitory activity of 4-dihydropyrimidine-2-thione (4a-h) and 2-amino-1,4-dihyropyrimidines (5a-h) series was observed with compound 4a and 4d identified as the most potent compounds with IC50 values of 0.17±0.01 and 0...
October 11, 2016: Bioorganic Chemistry
Xiao-Juan Wang, Yin-Ping Gao, Nan-Nan Lu, Wei-Shuo Li, Ji-Fang Xu, Xiao-Ying Ying, Gang Wu, Mei-Hua Liao, Chao Tan, Ling-Xiao Shao, Ying-Mei Lu, Chen Zhang, Kohji Fukunaga, Feng Han, Yong-Zhong Du
Clinical treatment for vascular dementia still remains a challenge mainly due to Blood-Brain Barrier (BBB). Here, a micelle based on polysialic acid (PSA) which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was firstly chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behaviour over a period of 72 h with 3...
October 17, 2016: ACS Applied Materials & Interfaces
Shiqi Cheng, WeiWei Gao, Xin Xu, Hengyi Fan, Yingang Wu, Fei Li, Jianning Zhang, Xingen Zhu, Yan Zhang
Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice...
October 13, 2016: Brain Research Bulletin
Kayoko Kanamitsu, Ryosuke Arakawa, Yuichi Sugiyama, Tetsuya Suhara, Hiroyuki Kusuhara
The effect of drugs in the central nervous system (CNS) is closely related to occupancy of their target receptor. In this study, we integrated plasma concentrations, in vitro/in vivo data for receptor or protein binding, and in silico data, using a physiologically based pharmacokinetic model, to examine the predictability of receptor occupancy in humans. The occupancy of the dopamine D2 receptor and the plasma concentrations of the antipsychotic drugs quetiapine and perospirone in humans were collected from the literature or produced experimentally...
July 30, 2016: Drug Metabolism and Pharmacokinetics
Jie Wu, Yiguang Tian, Shanping Wang, Marco Pistolozzi, Ya Jin, Ting Zhou, Gaurab Roy, Ling Xu, Wen Tan
An increase activity of butyrylcholinesterase is believed to contribute to Alzheimer's disease. Bambuterol is a known potent inhibitor of butyrylcholinesterase, but it has undesired cardiac effects and less lipophilicity. Thirteen bambuterol analogues were synthesized using 1-(3, 5-dihydroxyphenyl) ethanone as a starting material. In-vitro cholinesterase assay established that the majority of the compounds are specific butyrylcholinesterase inhibitors. Out of the 13 compounds, two bambuterol derivatives, BD-6 and BD-11 exhibited similar efficacies in inhibiting butyrylcholinesterase with fewer effects on heart and enhanced possibilities of permeating through the blood-brain barrier as compared to bambuterol...
August 26, 2016: European Journal of Medicinal Chemistry
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