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https://www.readbyqxmd.com/read/28533891/nuclear-uptake-of-an-amino-terminal-fragment-of-apolipoprotein-e4-promotes-cell-death-and-localizes-within-microglia-of-the-alzheimer-s-disease-brain
#1
Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn
Although harboring the apolipoprotein E4 (APOE4) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28529158/evaluation-of-direct-and-cell-mediated-triple-gene-therapy-in-spinal-cord-injury-in-rats
#2
Rustem Robertovich Islamov, Andrey Alexandrovich Izmailov, Mikhail Evgenyevich Sokolov, Philip Olegovich Fadeev, Farid Vagizovich Bashirov, Anton Alexandrovich Eremeev, Gulnara Ferdinantovna Shaymardanova, Maxim Michaylovich Shmarov, Boris Savelyevich Naroditskiy, Yuri Alexandrovich Chelyshev, Igor Aleksandrovich Lavrov, András Palotás
Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs)...
May 18, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28524415/ndrg4-an-early-detection-marker-for-colorectal-cancer-is-specifically-expressed-in-enteric-neurons
#3
N Vaes, M H F M Lentjes, M J Gijbels, G Rademakers, K L Daenen, W Boesmans, K A D Wouters, A Geuzens, X Qu, H P J Steinbusch, B P F Rutten, S H Baldwin, K A Sharkey, R M W Hofstra, M van Engeland, P Vanden Berghe, V Melotte
BACKGROUND: Promoter methylation of N-myc Downstream-Regulated Gene 4 (NDRG4) in fecal DNA is an established early detection marker for colorectal cancer (CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. METHODS: We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans...
May 19, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28522972/recent-advances-in-the-study-of-bipolar-rod-shaped-microglia-and-their-roles-in-neurodegeneration
#4
Ngan Pan Bennett Au, Chi Him Eddie Ma
Microglia are the resident immune cells of the central nervous system (CNS) and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28516078/subependymal-giant-cell-astrocytoma-presenting-with-tumoral-bleeding-a-case-report
#5
Jae-Young Kim, Tae-Young Jung, Kyung-Hwa Lee, Seul-Kee Kim
We report a rare case of subependymal giant cell astrocytoma (SEGA) associated with tumoral bleeding in a pediatric patient without tuberous sclerosis complex (TSC). A 10-year-old girl presented with a 2-week history of an increasingly aggravating headache. Brain magnetic resonance imaging revealed an approximately 3.6-cm, well-defined, heterogeneously enhancing mass with multistage hemorrhages on the right-sided foramen of Monro. The tumor was completely resected using a transcallosal approach. Intraoperatively, the mass presented as a gray-colored firm tumor associated with acute and subacute hemorrhages...
April 2017: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/28511006/novel-focused-ultrasound-gene-therapy-approach-noninvasively-restores-dopaminergic-neuron-function-in-a-rat-parkinson-s-disease-model
#6
Brian P Mead, Namho Kim, G Wilson Miller, David Hodges, Panagiotis Mastorakos, Alexander L Klibanov, James W Mandell, Jay Hirsh, Jung Soo Suk, Justin Hanes, Richard J Price
Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy...
May 18, 2017: Nano Letters
https://www.readbyqxmd.com/read/28507511/distribution-of-elovl4-in-the-developing-and-adult-mouse-brain
#7
David M Sherry, Blake R Hopiavuori, Megan A Stiles, Negar S Rahman, Kathryn G Ozan, Ferenc Deak, Martin-Paul Agbaga, Robert E Anderson
ELOngation of Very Long chain fatty acids (ELOVL)-4 is essential for the synthesis of very long chain-fatty acids (fatty acids with chain lengths ≥ 28 carbons). The functions of ELOVL4 and its very long-chain fatty acid products are poorly understood at present. However, mutations in ELOVL4 cause neurodevelopmental or neurodegenerative diseases that vary according to the mutation and inheritance pattern. Heterozygous inheritance of different ELOVL4 mutations causes Stargardt-like Macular Dystrophy or Spinocerebellar Ataxia type 34...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28500326/intranasal-drug-delivery-of-small-interfering-rna-targeting-beclin1-encapsulated-with-polyethylenimine-pei-in-mouse-brain-to-achieve-hiv-attenuation
#8
Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M Dever, Madhavan Nair, Nazira El-Hage
We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494166/ocular-safety-of-intravitreal-connective-tissue-growth-factor-neutralizing-antibody
#9
Tahmineh Motevasseli, Narsis Daftarian, Mozhgan Rezaei Kanavi, Hamid Ahmadieh, Abouzar Bagheri, Seyed Bagher Hosseini, Shabnam Ansari, Zahra-Soheila Soheili
PURPOSE: To detect the safety of intravitreal injection of anti-connective tissue growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing antibody for experimental animal studies. METHODS: Forty-five Lister Hooded male pigmented rats were divided into five groups that received IVAC (2 μl) corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 μg/ml (E), equal to 1.25, 2.5, 6.25, and 12.5 µg/ml of antibody concentration in rat vitreous, respectively...
May 11, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28493093/insights-from-mathematical-modeling-for-convection-enhanced-intraputamenal-delivery-of-gdnf
#10
Elena Belova, Christopher L Shaffer, Patrick E Trapa
Glial cell line-derived neurotrophic factor (GDNF) is a potential therapy for Parkinson's disease (PD) promoting survival and functional recovery of dopaminergic neurons when delivered to the degenerated striatum. To study the aspects of intraputamenal delivery of GDNF, a mathematical model of recombinant methionyl human GDNF (r-metHuGDNF) convection in the human putamen has been developed. The convection-enhanced delivery infusions of r-metHuGDNF were simulated at rates up to 5 μL/min. The high-rate infusions (≥1 μL/min) permit rapid and uniform distribution of drug with up to 75% of the distribution volume having a concentration within 5% of the infusate concentration...
May 11, 2017: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28486224/long-term-neuropathological-changes-associated-with-cerebral-palsy-in-a-nonhuman-primate-model-of-hypoxic-ischemic-encephalopathy
#11
Ryan M McAdams, Bobbi Fleiss, Christopher Traudt, Leslie Schwendimann, Jessica M Snyder, Robin L Haynes, Niranjana Natarajan, Pierre Gressens, Sandra E Juul
BACKGROUND: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. METHODOLOGY: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO)...
May 10, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28481241/biomarker-and-histopathology-evaluation-of-patients-with-recurrent-glioblastoma-treated-with-galunisertib-lomustine-or-the-combination-of-galunisertib-and-lomustine
#12
David Capper, Andreas von Deimling, Alba A Brandes, Antoine F Carpentier, Santosh Kesari, Juan M Sepulveda-Sanchez, Helen R Wheeler, Olivier Chinot, Lawrence Cher, Joachim P Steinbach, Pol Specenier, Jordi Rodon, Ann Cleverly, Claire Smith, Ivelina Gueorguieva, Colin Miles, Susan C Guba, Durisala Desaiah, Shawn T Estrem, Michael M Lahn, Wolfgang Wick
Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations...
May 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473192/characterization-of-a-cerebral-palsy-like-model-in-rats-analysis-of-gait-pattern-and-of-brain-and-spinal-cord-motor-areas
#13
Adriana Souza Dos Santos, Wellington de Almeida, Bruno Popik, Bruno Marques Sbardelotto, Márcia Miranda Torrejais, Marcelo Alves de Souza, Lígia Aline Centenaro
In an attempt to propose an animal model that reproduces in rats the phenotype of cerebral palsy, this study evaluated the effects of maternal exposure to bacterial endotoxin associated with perinatal asphyxia and sensorimotor restriction on gait pattern, brain and spinal cord morphology. Two experimental groups were used: Control Group (CTG) - offspring of rats injected with saline during pregnancy and Cerebral Palsy Group (CPG) - offspring of rats injected with lipopolysaccharide during pregnancy, submitted to perinatal asphyxia and sensorimotor restriction for 30days...
May 1, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28469524/olfactory-neuroepithelial-neural-progenitor-cells-from-subjects-with-bipolar-i-disorder
#14
Yonglin Gao, Welby Winstead, Zhenmin Lei, Chengliang Lu, Fred J Roisen, Rif S El-Mallakh
BACKGROUND: Research into the pathophysiology of bipolar disorder (BD) is limited by the inability to examine brain cellular processes in subjects with the illness. METHODS: Endoscopic biopsy was performed in subjects with bipolar I disorder to establish olfactory neural progenitor (ONP) cell lines. Olfactory function was assessed prebiopsy and postbiopsy using the University of Pennsylvania Smell Identification Test (UPSIT). Cells were characterized to determine their lineage...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28466093/myeloperoxidase-immunoreactive-cells-are-significantly-increased-in-brain-areas-affected-by-neurodegeneration-in-parkinson-s-and-alzheimer-s-disease
#15
Sandra Gellhaar, Dan Sunnemark, Håkan Eriksson, Lars Olson, Dagmar Galter
Myeloperoxidase (MPO) is a key enzyme in inflammatory and degenerative processes, although conflicting reports have been presented concerning its expression in the brain. We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically healthy individuals and patients with Parkinson's disease (PD) or Alzheimer's disease (AD; n = 10-25). We also investigated two rodent PD models. MPO immunoreactivity (ir) was detected in monocytes, perivascular macrophages and amoeboid microglia in the human brain parenchyma, whereas no co-localization with glial fibrillary acidic protein (GFAP) ir was observed...
May 2, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28463804/encapsulated-cell-device-approach-for-combined-electrical-stimulation-and-neurotrophic-treatment-of-the-deaf-cochlea
#16
W S Konerding, H Janssen, P Hubka, J Tornøe, P Mistrik, L Wahlberg, T Lenarz, A Kral, V Scheper
Profound hearing impairment can be overcome by electrical stimulation (ES) of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Thus, SGN survival is critical for CI efficacy. Application of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce SGN degeneration following deafness. We tested a novel method for local, continuous GDNF-delivery in combination with ES via a CI. The encapsulated cell (EC) device contained a human ARPE-19 cell-line, genetically engineered for secretion of GDNF...
April 25, 2017: Hearing Research
https://www.readbyqxmd.com/read/28461173/poly-adp-ribose-polymerase-1-regulates-microglia-mediated-decrease-of-endothelial-tight-junction-integrity
#17
Abbas Rezaeian Mehrabadi, Minna A Korolainen, Gary Odero G, Donald W Miller, Tiina M Kauppinen
Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28459572/neuroprotective-and-antineuroinflammatory-effects-of-hydroxyl-functionalized-stilbenes-and-2-arylbenzo-b-furans
#18
Pei-Chun Chen, Wei-Jern Tsai, Yune-Fang Ueng, Tsai-Teng Tzeng, Hsiang-Ling Chen, Pei-Ru Zhu, Chia-Hsiang Huang, Young-Ji Shiao, Wen-Tai Li
The drugs currently used to treat Alzheimer's disease (AD) are limited in the benefits they confer, and no medication has been clearly proven to cure or delay the progression of AD. Most candidate AD drugs are meant to reduce the production, aggregation, and toxicity of amyloid β (Aβ) or to promote Aβ clearance. Herein, we demonstrate the efficient synthesis of hydroxyl-functionalized stilbene and 2-arylbenzo[b]furan derivatives and report on the neuroprotective and anti-inflammatory effects of these phenolic compounds in vitro and in an animal model...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28453954/local-delivery-of-chondroitinase-abc-with-or-without-stromal-cell-derived-factor-1%C3%AE-promotes-functional-repair-in-the-injured-rat-spinal-cord
#19
Malgosia M Pakulska, Charles H Tator, Molly S Shoichet
Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradation of the glial scar, using chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells (NPCs), using stromal cell-derived factor 1α (SDF)...
April 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28453876/age-associated-changes-in-the-blood-brain-barrier-comparative-studies-in-human-and-mouse
#20
Emily F Goodall, Chunfang Wang, Julie E Simpson, David J Baker, David R Drew, Paul R Heath, M Jill Saffrey, Ignacio A Romero, Stephen B Wharton
AIMS: While vascular pathology is a common feature of a range of neurodegenerative diseases, we hypothesised that vascular changes occur in association with normal ageing. Therefore we aimed to characterise age-associated changes in the blood brain barrier (BBB) in human and mouse cohorts. METHODS: Immunohistochemistry and Evans Blue assays were used to characterise BBB dysfunction (tight junction protein expression and serum plasma protein accumulation), vascular pathology (pericyte loss and vascular density) and glial pathology (astrocyte and microglial density) in ageing neurological control human pre-frontal cortex (a total of 23 cases from 5 age groups representing the spectrum of young adult to old age: 20-30yrs, 31-45yrs, 46-60yrs, 61-75yrs and 75+) and C57BL/6 mice (3 month, 12 month, 18 month and 24 month, n=5/6 per group)...
April 28, 2017: Neuropathology and Applied Neurobiology
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