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https://www.readbyqxmd.com/read/28917978/sen1500-a-novel-oral-amyloid-%C3%AE-aggregation-inhibitor-attenuates-brain-pathology-in-a-mouse-model-of-alzheimer-s-disease
#1
D Brunner, S Flunkert, J Neddens, S Duller, D I C Scopes, J M Treherne, B Hutter-Paier
INTRODUCTION: Amyloid-β (Aβ) aggregation is thought to be a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The development of new drugs inhibiting the Aβ aggregation process is, therefore, important. SEN1500, an orally bioavailable and CNS-penetrant Aβ aggregation inhibitor, has previously been shown to reduce spatial learning and memory deficits in an APP transgenic mouse model. To verify that the pharmacological properties of SEN1500 are not unique to this model, we investigated brain Aβ pathology, neuroinflammation, as well as memory in a different mouse model of AD expressing the human amyloid precursor protein with Swedish and London mutations (APPSL)...
September 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28917705/long-term-retention-of-ecm-hydrogel-after-implantation-into-a-sub-acute-stroke-cavity-reduces-lesion-volume
#2
Harmanvir Ghuman, Madeline Gerwig, Francesca J Nicholls, Jessie Liu, Julia Donnelly, Stephen F Badylak, Michel Modo
Salvaging or functional replacement of damaged tissue caused by stroke in the brain remains a major therapeutic challenge. In situ gelation and retention of a hydrogel bioscaffold composed of 8 mg/mL extracellular matrix (ECM) can induce a robust invasion of cells within 24 hours and potentially promote a structural remodeling to replace lost tissue. Herein, we demonstrate a long-term retention of ECM hydrogel within the lesion cavity. A decrease of approximately 32% of ECM volume is observed over 12 weeks...
September 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28883901/loss-of-sigma-1-receptor-chaperone-promotes-astrocytosis-and-enhances-the-nrf2-antioxidant-defense
#3
Tzu-Yu Weng, Denise T Hung, Tsung-Ping Su, Shang-Yi A Tsai
Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28879430/high-mobility-group-box-1-enhances-hyperthermia-induced-seizures-and-secondary-epilepsy-associated-with-prolonged-hyperthermia-induced-seizures-in-developing-rats
#4
Masanori Ito, Hisaaki Takahashi, Hajime Yano, Yusuke I Shimizu, Yoshiaki Yano, Yoshito Ishizaki, Junya Tanaka, Eiichi Ishii, Mitsumasa Fukuda
Levels of high mobility group box 1 (HMGB1), an important inflammatory mediator, are high in the serum of febrile seizure (FS) patients. However, its roles in FS and secondary epilepsy after prolonged FS are poorly understood. We demonstrate HMGB1's role in the pathogenesis of hyperthermia-induced seizures (HS) and secondary epilepsy after prolonged hyperthermia-induced seizures (pHS). In the first experiment, 14-15-day-old male rats were divided into four groups: high-dose HMGB1 (100 μg), moderate-dose (10 μg), low-dose (1 μg), and control...
September 6, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28865458/salutary-effects-of-glibenclamide-during-the-chronic-phase-of-murine-experimental-autoimmune-encephalomyelitis
#5
Volodymyr Gerzanich, Tapas K Makar, Poornachander Reddy Guda, Min Seong Kwon, Jesse A Stokum, Seung Kyoon Woo, Svetlana Ivanova, Alexander Ivanov, Rupal I Mehta, Alexandra Brooke Morris, Joseph Bryan, Christopher T Bever, J Marc Simard
BACKGROUND: In multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), inflammation is perpetuated by both infiltrating leukocytes and astrocytes. Recent work implicated SUR1-TRPM4 channels, expressed mostly by astrocytes, in murine EAE. We tested the hypothesis that pharmacological inhibition of SUR1 during the chronic phase of EAE would be beneficial. METHODS: EAE was induced in mice using myelin oligodendrocyte glycoprotein (MOG) 35-55. Glibenclamide (10 μg/day) was administered beginning 12 or 24 days later...
September 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28842420/conditional-deletion-of-prnp-rescues-behavioral-and-synaptic-deficits-after-disease-onset-in-transgenic-alzheimer-s-disease
#6
Santiago V Salazar, Christopher Gallardo, Adam C Kaufman, Charlotte S Herber, Laura T Haas, Sophie Robinson, Jean C Manson, Michael K Lee, Stephen M Strittmatter
Biochemical and genetic evidence implicate soluble oligomeric amyloid-beta (Aβo) in triggering Alzheimer's disease (AD) pathophysiology. Moreover, constitutive deletion of the Aβo-binding cellular prion protein (PrP(C)) prevents development of memory deficits in APPswe/PS1ΔE9 mice, a model of familial AD. Here, we define the role of PrP(C) to rescue or halt established AD endophenotypes in a therapeutic disease-modifying time window after symptom onset. Deletion of Prnp at either 12 or 16 months of age fully reverses hippocampal synapse loss, and completely rescues pre-existing behavioral deficits by 17 months...
August 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28804999/diversity-of-astroglial-responses-across-human-neurodegenerative-disorders-and-brain-aging
#7
Isidro Ferrer
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28756201/multiple-mild-traumatic-brain-injury-in-the-rat-produces-persistent-pathological-alterations-in-the-brain
#8
Diane M Brooks, Sarjubhai A Patel, Eric D Wohlgehagen, Erin O Semmens, Alan Pearce, Edmond A Sorich, Thomas F Rau
Multiple mild traumatic brain injury (mmTBI), in certain cases, produces persistent symptoms. However, the molecular mechanisms underlying these symptoms remain unclear. Here, we demonstrate extended pathological changes in the rat brain following mmTBI. Using the lateral fluid percussion (LFP) technique we exposed adult male Wistar rats to a mild TBI (mTBI) once a week for four weeks and compared them to surgical shams. At 90days following the last TBI or sham procedure the animals were cognitively tested in the Morris Water Maze (MWM), euthanized, and the brains removed for immunohistochemistry...
July 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28749290/granulomatous-encephalomyelitis-in-a-false-gharial-tomistoma-schlegelii-associated-with-a-novel-chlamydia-species
#9
Marjorie Bercier, Darryl J Heard, Alexandra M Goe, Ember Epperson, Jeffrey R Abbott, April L Childress, James F X Wellehan
A 5-yr-old, captive, hatched, female false gharial (Tomistoma schlegelii) presented with a 1-mo history of cervical spinal curvature. Antemortem diagnostics, including blood work, electromyography, muscle biopsies, and advanced imaging tests, were either within reference ranges or did not identify any specific etiology. Necropsy revealed extensive, marked, chronic granulomatous encephalomyelitis along with neuronal necrosis, rarefaction, gliosis, and astrocytosis of the white and gray matter of the cerebrum, cerebellum, brainstem, and spinal cord...
June 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28694468/interactome-and-reciprocal-activation-of-pathways-in-topical-mesenchymal-stem-cells-and-the-recipient-cerebral-cortex-following-traumatic-brain-injury
#10
Ping K Lam, Kevin K W Wang, Anthony W I Lo, Cindy S W Tong, Don W C Ching, Kenneth Wong, Zhihui Yang, Themis Kong, Kin K Y Lo, Richard K W Choy, Paul B S Lai, George K C Wong, Wai S Poon
In this study, GFP-MSCs were topically applied to the surface of cerebral cortex within 1 hour of experimental TBI. No treatment was given to the control group. Three days after topical application, the MSCs homed to the injured parenchyma and improved the neurological function. Topical MSCs triggered earlier astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and reduced neuronal damaged was found in the penumbral at day 14 apoptosis...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680301/functional-characterization-of-resting-and-adenovirus-induced-reactive-astrocytes-in-three-dimensional-culture
#11
Junsung Woo, Sun-Kyoung Im, Heejung Chun, Soon-Young Jung, Soo-Jin Oh, Nakwon Choi, C Justin Lee, Eun-Mi Hur
Brain is a rich environment where neurons and glia interact with neighboring cells as well as extracellular matrix in three-dimensional (3D) space. Astrocytes, which are the most abundant cells in the mammalian brain, reside in 3D space and extend highly branched processes that form microdomains and contact synapses. It has been suggested that astrocytes cultured in 3D might be maintained in a less reactive state as compared to those growing in a traditional, two-dimensional (2D) monolayer culture. However, the functional characterization of the astrocytes in 3D culture has been lacking...
June 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28662822/matrix-metalloproteinases-neural-extracellular-matrix-and-central-nervous-system-pathology
#12
Ciro De Luca, Michele Papa
The functionality and stability of the central nervous system (CNS) pabulum, called neural extracellular matrix (nECM), is paramount for the maintenance of a healthy network. The loosening or the damage of the scaffold disrupts synaptic transmission with the consequent imbalance of the neurotransmitters, reactive cells invasion, astrocytosis, new matrix deposition, digestion of the previous structure and ultimately, maladaptive plasticity with the loss of neuronal viability. nECM is constantly affected by CNS disorders, particularly in chronic modifying such as neurodegenerative disease, or in acute/subacute with chronic sequelae, like cerebrovascular and inflammatory pathology...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28609381/remote-ischemic-conditioning-preserves-cognition-and-motor-coordination-in-a-mouse-model-of-traumatic-brain-injury
#13
Alexander J Sandweiss, Asad Azim, Kareem Ibraheem, Tally M Largent-Milnes, Peter Rhee, Todd W Vanderah, Bellal Joseph
INTRODUCTION: Management of traumatic brain injury (TBI) is focused on minimizing or preventing secondary brain injury. Remote ischemic conditioning (RIC) is an established treatment modality that has been shown to improve patient outcomes in different clinical settings by influencing inflammatory insults. In a clinical trial, RIC showed amelioration of SB100 and NSE. The aim of our study was to further elucidate the mechanisms and outcome when applying RIC in a mouse model of traumatic brain injury...
June 13, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28598192/evaluation-of-a-human-neural-stem-cell-culture-method-for-prediction-of-the-neurotoxicity-of-anti-epileptics
#14
Abdal-Jabbar Al-Rubai, Peter Wigmore, Margaret K Pratten
Human neural stem cells have been proposed as an in vitro model to predict neurotoxicity. In this study, the potential of in vitro cultures of human-derived neurospheres to predict the effects of various anti-epileptic drugs (sodium valproate, phenytoin, carbamazepine and phenobarbitone) was evaluated. In general, these drugs had no significant effects on cell viability, total cellular protein, and neuronal process length at low doses, but at high doses these parameters were reduced significantly. Therapeutic doses of sodium valproate and phenytoin had a clear effect on neurosphere size and cell migration, with a significant reduction in both parameters when compared with the control group...
May 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28536976/memory-and-learning-dysfunction-following-copper-toxicity-biochemical-and-immunohistochemical-basis
#15
Jayantee Kalita, Vijay Kumar, Usha K Misra, Himangsu K Bora
The prototype disease of Cu toxicity in human is Wilson disease, and cognitive impairment is the presenting symptom of it. There is no study correlating Cu-induced excitotoxicity, apoptosis, and astrocytic reaction with memory dysfunction. We report excitotoxicity, apoptosis, and astrocytic reaction of the hippocampus and frontal cortex with memory dysfunction in rat model of Cu toxicity. Thirty-six rats were divided into group I (control) and group II (100 mg/kgBwt/day CuSO4 orally). Y-maze was performed for memory and learning at 0, 30, 60, and 90 days...
May 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28475165/molecular-imaging-of-neuroinflammation-in-neurodegenerative-dementias-the-role-of-in-vivo-pet-imaging
#16
REVIEW
Chiara Cerami, Leonardo Iaccarino, Daniela Perani
Neurodegeneration elicits neuroinflammatory responses to kill pathogens, clear debris and support tissue repair. Neuroinflammation is a dynamic biological response characterized by the recruitment of innate and adaptive immune system cells in the site of tissue damage. Resident microglia and infiltrating immune cells partake in the restoration of central nervous system homeostasis. Nevertheless, their activation may shift to chronic and aggressive responses, which jeopardize neuron survival and may contribute to the disease process itself...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28464005/a-tailored-mouse-model-of-cln2-disease-a-nonsense-mutant-for-testing-personalized-therapies
#17
Ryan D Geraets, Logan M Langin, Jacob T Cain, Camille M Parker, Rosanna Beraldi, Attila D Kovacs, Jill M Weimer, David A Pearce
The Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, result from mutations in over a dozen genes. Although, adults are susceptible, the NCLs are frequently classified as pediatric neurodegenerative diseases due to their greater pediatric prevalence. Initial clinical presentation usually consists of either seizures or retinopathy but develops to encompass both in conjunction with declining motor and cognitive function. The NCLs result in premature death due to the absence of curative therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28451919/a-novel-conditional-sgsh-knockout-mouse-model-recapitulates-phenotypic-and-neuropathic-deficits-of-sanfilippo-syndrome
#18
Adeline A Lau, Barbara M King, Carly L Thorsen, Sofia Hassiotis, Helen Beard, Paul J Trim, Lauren S Whyte, Sarah J Tamang, Stephen K Duplock, Marten F Snel, John J Hopwood, Kim M Hemsley
Mucopolysaccharidosis (MPS) type IIIA, or Sanfilippo syndrome, is a neurodegenerative lysosomal storage disorder caused by a deficiency of the lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), involved in the catabolism of heparan sulfate. The clinical spectrum is broad and the age of symptom onset and the degree of preservation of cognitive and motor functions appears greatly influenced by genotype. To explore this further, we generated a conditional knockout (Sgsh (KO) ) mouse model with ubiquitous Sgsh deletion, and compared the clinical and pathological phenotype with that of the spontaneous Sgsh (D31N) MPS-IIIA mouse model...
April 27, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28434162/isolation-of-astrocytes-displaying-myofibroblast-properties-and-present-in-multiple-sclerosis-lesions
#19
Nicolas Vedrenne, Vincent Sarrazy, Laurence Richard, Nelly Bordeau, Serge Battu, Fabrice Billet, Alexis Desmoulière
A wide heterogeneity of lesions can affect the central nervous system (CNS). In all situations where neurons are damaged, including multiple sclerosis (MS), a common reactive astrocytosis is present. Sedimentation field-flow fractionation (SdFFF) was used to sort astrocyte subpopulations. After SdFFF elution, cells, prepared from rat newborn cortex, were cultured and analyzed by immunocytofluorescence for glial fibrillary acidic protein (GFAP) and α-smooth muscle (SM) actin (a specific marker for myofibroblasts) expression...
August 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28420695/adeno-associated-viral-9-mediated-cdk5-inhibitory-peptide-reverses-pathologic-changes-and-behavioral-deficits-in-the-alzheimer-s-disease-mouse-model
#20
Yong He, Suyue Pan, Miaojing Xu, Rongni He, Wei Huang, Pingping Song, Jianou Huang, Han-Ting Zhang, Yafang Hu
Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35, phosphorylates multiple substrates and plays an essential role in the development and function of the CNS; however, proteolytic production of p25 from p35 under stress conditions leads to the inappropriate activation of Cdk5 and contributes to hyperphosphorylation of τ and other substrates that are related to the pathogenesis of Alzheimer's disease. Selective inhibition of aberrant Cdk5 activity via genetic overexpression of Cdk5 inhibitory peptide (CIP) reduces pathologic changes and prevents brain atrophy and memory loss in p25-transgenic mice...
April 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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