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https://www.readbyqxmd.com/read/29913220/nootropic-nanocomplex-with-enhanced-blood-brain-barrier-permeability-for-treatment-of-traumatic-brain-injury-associated-neurodegeneration
#1
REVIEW
Jeongmin Park, Eunshil Choi, Seulgi Shin, Sungsu Lim, Dohee Kim, Suji Baek, Kang Pa Lee, Jae Jun Lee, Byeong Han Lee, Bokyung Kim, Keunsoo Jeong, Ja-Hyun Baik, Yun Kyung Kim, Sehoon Kim
Traumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration...
June 15, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29913196/pntx2-6-or-%C3%AE-cntx-pn2a-a-toxin-from-phoneutria-nigriventer-spider-venom-releases-l-glutamate-from-rat-brain-synaptosomes-involving-na-and-ca-2-channels-and-changes-protein-expression-at-the-blood-brain-barrier
#2
Carolina Nunes da Silva, Rosângela Silva Lomeo, Fernanda Silva Torres, Marcia Helena Borges, Marta Cordeiro Nascimento, Maria Helena Rodrigues Mesquita-Britto, Catarina Rapôso, Adriano Monteiro de Castro Pimenta, Maria Alice da Cruz-Höfling, Dawidson Assis Gomes, Maria Elena de Lima
PhTx2 is the most toxic fraction from the venom of the spider Phoneutria nigriventer, being responsible to sodium entry into cortical synaptosomes, increasing the release of neurotransmitters, such as l-glutamate (L-Glu) and; acetylcholine. In this study, we investigated the action of a toxin purified from; PhTx2 fraction, called PnTx2-6 or δ-CNTX-Pn2a, on L-Glu release from rat; brain cortex synaptosomes, as well as its ability to induce blood-brain barrier permeability. PnTx2-6 increased L-Glu release from rat cortical brain synaptosomes in a time- and dose-dependent manner (EC50 = ∼20 nM; Tm = 16min), as measured by a fluorimetric method...
June 15, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29911470/endothelial-cells-are-critical-regulators-of-iron-transport-in-a-model-of-the-human-blood-brain-barrier
#3
Brian Chiou, Emma H Neal, Aaron B Bowman, Ethan S Lippmann, Ian A Simpson, James R Connor
Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29910805/ip-10-promotes-blood-brain-barrier-damage-by-inducing-tumor-necrosis-factor-alpha-production-in-japanese-encephalitis
#4
Ke Wang, Haili Wang, Wenjuan Lou, Longhuan Ma, Yunchuan Li, Nan Zhang, Chong Wang, Fang Li, Muhammad Awais, Shengbo Cao, Ruiping She, Zhen F Fu, Min Cui
Japanese encephalitis is a neuropathological disorder caused by Japanese encephalitis virus (JEV), which is characterized by severe pathological neuroinflammation and damage to the blood-brain barrier (BBB). Inflammatory cytokines/chemokines can regulate the expression of tight junction (TJ) proteins and are believed to be a leading cause of BBB disruption, but the specific mechanisms remain unclear. IP-10 is the most abundant chemokine produced in the early stage of JEV infection, but its role in BBB disruption is unknown...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910674/low-dose-evans-blue-dye-for-near-infrared-fluorescence-imaging-in-photothrombotic-stroke-model
#5
Hye-Won Ryu, Wonbong Lim, Danbi Jo, Subin Kim, Jong Tae Park, Jung-Joon Min, Hoon Hyun, Hyung-Seok Kim
Background: Evans blue dye (EBD) is the most common indicator to analyze the extent of blood-brain barrier (BBB) breakdown in several neurological disease models. However, the high-dose of EBD (51.9 mg/kg) is usually required for visualization of blue color by the human eye that brings potential safety issues. Methods: To solve this problem, low-dose of EBD was applied for the near-infrared (NIR) fluorescence-assisted quantitation of BBB breakdown in photothrombotic stoke model. Animals were allocated to seven dose groups ranging from 1...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29909686/improved-healing-after-the-co-transplantation-of-ho-1-and-bdnf-overexpressed-mesenchymal-stem-cells-in-the-subacute-spinal-cord-injury-of-dogs
#6
Imdad Ullah Khan, Yongseok Yoon, Ahyoung Kim, Kwang Rae Jo, Kyeung Uk Choi, Taeseong Jung, Namyul Kim, YeonSung Son, Wan Hee Kim, Oh-Kyeong Kweon
Abundant expression of proinflammatory cytokines after a spinal cord injury (SCI) creates an inhibitory microenvironment for neuroregeneration. The mesenchymal stem cells help to mitigate the inflammation and improve neural growth and survival. For this purpose, we potentiated the function of adipose-derived mesenchymal stem cells (Ad-MSCs) by transfecting them with brain-derived neurotrophic factor (BDNF) and heme oxygenase-1 (HO-1), through a lentivirus, to produce BDNF overexpressed Ad-MSCs (BDNF-MSCs), and HO-1 overexpressed Ad-MSCs (HO-1-MSCs)...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29908130/designed-macrocyclic-peptides-as-nanomolar-amyloid-inhibitors-based-on-minimal-recognition-elements
#7
Anna Spanopoulou, Luzia Heidrich, Hong-Ru Chen, Christina Frost, Dean Hrle, Eleni Malideli, Kathleen Hille, Alexandros Grammatikopoulos, Jürgen Bernhagen, Martin Zacharias, Gerhard Rammes, Aphrodite Kapurniotu
Amyloid self-assembly is linked to the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), but so far none of the anti-amyloid molecules has reached the clinic. Macrocyclic peptides belong to the most attractive drug candidates. Here we present macrocyclic peptides (MCIPs) designed using minimal IAPP-derived recognition elements as a novel class of nanomolar amyloid inhibitors of both Abeta40(42) and IAPP or Abeta40(42) alone and show that chirality controls inhibitor selectivity. Sequence optimization led to the discovery of an Abeta40(42)-selective MCIP exhibiting high proteolytic stability in human plasma and human blood-brain-barrier (BBB) crossing ability in a cell model, two highly desirable properties for anti-amyloid drugs in AD...
June 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29907754/nano-particle-mediated-inhibition-of-parkinson-s-disease-using-computational-biology-approach
#8
Aman Chandra Kaushik, Shiv Bharadwaj, Sanjay Kumar, Dong-Qing Wei
Parkinson's disease (PD) arises as neurodegenerative disorder and characterized by progressive deterioration of motor functions due to forfeiture of dopamine-releasing neurons. During PD, neurons at stake loss their functionality that results into cognition impairment and forgetfulness, commonly called as dementia. Recently, nanoparticles (NPs) have been reported for easy drug delivery through blood-brain barrier (BBB) into the central nervous system (CNS) against the conventional drug delivery systems. However, present study attempted to elucidate the α-synuclein activity, a major factor casing PD, in presence of its inhibitor cerium oxide (CeO2 ) nanoparticle via computational biology approach...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29906474/acteoside-protects-against-6-ohda-induced-dopaminergic-neuron-damage-via-nrf2-are-signaling-pathway
#9
Maiquan Li, Fei Zhou, Tao Xu, Huaxin Song, Baiyi Lu
Acteoside has been reported to have antioxidant and neuroprotective effect, which is a promising therapeutic way in prevention and treatment of Parkinson's disease. The present study was aimed to understand the neuroprotective effect of acteoside and to elucidate its underlying mechanism. 6-hydroxydopamine (6-OHDA)-induced neural damage in zebrafish model was used to study the protective effect of acteoside on Parkinson disease (PD). Locomotion behavioral test showed that acteoside could prevent 6-OHDA-stimulated movement disorders...
June 12, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29905772/nrf2-deficiency-exacerbates-obesity-induced-oxidative-stress-neurovascular-dysfunction-blood-brain-barrier-disruption-neuroinflammation-amyloidogenic-gene-expression-and-cognitive-decline-in-mice-mimicking-the-aging-phenotype
#10
Stefano Tarantini, M Noa Valcarcel-Ares, Andriy Yabluchanskiy, Zsuzsanna Tucsek, Peter Hertelendy, Tamas Kiss, Tripti Gautam, Xin A Zhang, William E Sonntag, Rafael de Cabo, Eszter Farkas, Michael H Elliott, Michael T Kinter, Ferenc Deak, Zoltan Ungvari, Anna Csiszar
Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment...
June 14, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29905040/-promotion-of-transplanted-collagen-scaffolds-combined-with-brain-derived-neurotrophic-factor-for-axonal-regeneration-and-motor-function-recovery-in-rats-after-transected-spinal-cord-injury
#11
Xi Chen, Yongheng Fan, Zhifeng Xiao, Xing Li, Bin Yang, Yannan Zhao, Xianglin Hou, Sufang Han, Jianwu Dai
Objective: To evaluate the effect of the combination of collagen scaffold and brain-derived neurotrophic factor (BDNF) on the repair of transected spinal cord injury in rats. Methods: Thirty-two Sprague-Dawley rats were randomly divided into 4 groups: group A (sham operation group), T 9 , T 10 segments of the spinal cord was only exposed; group B, 4-mm T 9 , T 10 segments of the spinal cord were resected; group C, 4-mm T 9 , T 10 segments of the spinal cord were resected and linear ordered collagen scaffolds (LOCS) with corresponding length was transplanted into lesion site; group D, 4-mm T 9 , T 10 segments of the spinal cord were resected and LOCS with collagen binding domain (CBD)-BDNF was transplanted into lesion site...
June 1, 2018: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/29904952/baicalin-effects-on-rats-with-spinal-cord-injury-by-anti-inflammatory-and-regulating-the-serum-metabolic-disorder
#12
Shufeng Kang, Shizhao Liu, Hongzhu Li, Dapeng Wang, Xiangbei Qi
Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 were detected by the enzyme-linked immunosorbent assay method...
June 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29904397/thymoquinone-reduces-spinal-cord-injury-by-inhibiting-inflammatory-response-oxidative-stress-and-apoptosis-via-ppar-%C3%AE-and-pi3k-akt-pathways
#13
Yinming Chen, Benlong Wang, Hai Zhao
The present study used a mild contusion injury in rat spinal cord to determine that thymoquinone reduces inflammatory response, oxidative stress and apoptosis in a spinal cord injury (SCI) rat model and to demonstrate its possible molecular mechanisms. The rats in the thymoquinone group received 30 mg/kg thymoquinone once daily by intragastric administration from 3 weeks after surgery. Hematoxylin and eosin staining, Basso, Beattie and Bresnahan (BBB) scale and tissue water content detection were used in the present study to analyze the effect of thymoquinone on SCI...
June 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29903719/electroacupuncture-a-new-approach-to-open-the-blood-brain-barrier-in-rats-recovering-from-middle-cerebral-artery-occlusion
#14
Jiangsong Zhang, Xianming Lin, Hui Zhou, Yuanyuan Chen, Shuangkai Xiao, Junyue Jiao, Yibin Zhao, Zhong Di
OBJECTIVE: To examine for an opening effect on the blood-brain barrier (BBB) in intact rats and rats with experimental ischaemia-reperfusion (I/R) during the recovery period after various electroacupuncture (EA) treatments with different time courses, and to determine whether there is a time-dependent effect. An additional objective was to determine whether this method could induce the penetration of nerve growth factor (NGF) through the BBB. METHODS: A middle cerebral artery occlusion (MCAO) model was first established...
June 14, 2018: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/29902901/-effects-of-emodin-on-oxidative-stress-and-inflammatory-response-in-rats-with-acute-spinal-cord-injury
#15
Huan-Huan Zeng, Ying-Ru Huang, Zi-Jian Li, Yi Wang, Song Zhang
This paper was aimed to investigate the effects of emodin on oxidative stress and inflammatory response in rats with acute spinal cord injury(SCI), and to explore the protective mechanism of emodin on neurons after SCI. Rat SCI models were established using a modified Allen's method. One hundred and ninety five Sprague-Dawley rats were randomly divded into sham (group A), model (group B), emodin group of 20 mg·kg⁻¹(group C), emodin group of 40 mg·kg⁻¹(group D), emodin group of 80 mg·kg⁻¹(group E)...
May 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29902485/a-nanoformulation-for-the-preferential-accumulation-in-adult-neurogenic-niches
#16
Catarina Praça, Akhilesh Rai, Tiago Santos, Ana C Cristovão, Sonia L Pinho, Romeo Cecchelli, Marie-Pierre Dehouck, Liliana Bernardino, Lino S Ferreira
Stimulation of adult neurogenesis by targeting the endogenous neural stem cells (NSCs), located in hippocampus and subventricular zone (SVZ), with nanoformulations has been proposed for brain repair in cases of neurodegenerative diseases. Unfortunately, it is relatively unknown the nanoformulation properties to facilitate their accumulation in the neurogenic niches after intravenous injection. Here, we have screened different gold-based formulations having variable morphology, surface chemistry and responsiveness to light for their capacity to cross the blood brain barrier (BBB) and accumulate preferentially in the neurogenic niches...
June 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29901990/increased-brain-exposure-of-an-alpha-synuclein-fibrillization-modulator-by-utilization-of-an-activated-ester-pro-drug-strategy
#17
Andrew Gerard Cairns, Ana Vazquez-Romero, Mohammad Mahdi-Moein, Jörgen Åden, Charles S Elmore, Akihiro Takano, Ryosuke Arakawa, Andrea Varrone, Fredrik Almqvist, Magnus Schou
Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha synuclein (α-syn) fibrillization in vitro. As a first step towards developing molecules from this scaffold as PET imaging agents, we were interested in evaluating their BBB permeability in non-human primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate -syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analog 14, were then radiolabeled with 11C (t1/2=20...
June 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29898739/longitudinal-chemokine-profile-expression-in-a-blood-brain-barrier-model-from-alzheimer-transgenic-versus-wild-type-mice
#18
J Vérité, T Janet, D Chassaing, B Fauconneau, H Rabeony, G Page
BACKGROUND: Alzheimer's disease is widely described since the discovery of histopathological lesions in Mrs. Auguste Deter in 1906. However to date, there is no effective treatment to deal with the many cellular and molecular alterations. The complexity is even higher with the growing evidence of involvement of the peripheral blood mononuclear cells (PBMCs). Indeed, monocytes and T cells are shown in the cerebral parenchyma of AD patients, and these cells grafted to the periphery are able to go through the blood-brain barrier (BBB) in transgenic mouse models...
June 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29897434/the-c-abl-inhibitor-radotinib-hcl-is-neuroprotective-in-a-preclinical-parkinson-s-disease-mouse-model
#19
Saebom Lee, Sangjune Kim, Yong Joo Park, Seung Pil Yun, Seung-Hwan Kwon, Donghoon Kim, Dong Yeon Kim, Jae Soo Shin, Dae Jin Cho, Gong Yeal Lee, Hyun Soo Ju, Hyo Jung Yun, Jae Hong Park, Wonjoong Richard Kim, Eun Ah Jung, Seulki Lee, Han Seok Ko
Accumulating evidence suggests that the nonreceptor tyrosine kinase c-Abl plays an important role in the progression of Parkinson's disease (PD) and c-Abl inhibition could be neuroprotective in PD and related α-synucleinopathies. Nilotinib, a c-Abl inhibitor, has shown improved motor and cognitive symptoms in PD patients. However, issues concerning blood-brain barrier (BBB) penetration, lack of selectivity, and safety still remain. Radotinib HCl is a selective Bcr-Abl kinase inhibitor that not only effectively access the brain, but also exhibits greater pharmacokinetic properties and safety profiles compared to Nilotinib and other c-Abl inhibitors...
April 20, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29897225/establishment-of-a-human-ipsc-and-nanofiber-based-microphysiological-blood-brain-barrier-system
#20
Dianjun Qi, Shaohua Wu, Haishuang Lin, Mitchell A Kuss, Yuguo Lei, Alexey Krasnoslobodtsev, Shaheen Ahmed, Chi Zhang, Hyung Joon Kim, Peng Jiang, Bin Duan
The blood-brain barrier (BBB) is an active and complex diffusion barrier that separates the circulating blood from the brain and extracellular fluid, regulates nutrient transportation, and provides protection against various toxic compounds and pathogens. Creating an in vitro microphysiological BBB system, particularly with relevant human cell types, will significantly facilitate the research of neuro-pharmaceutical drug delivery, screening, and transport, as well as improve our understanding of pathologies that are due to BBB damage...
June 13, 2018: ACS Applied Materials & Interfaces
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