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https://www.readbyqxmd.com/read/29658944/an-in-vivo-model-of-functional-and-vascularized-human-brain-organoids
#1
Abed AlFatah Mansour, J Tiago Gonçalves, Cooper W Bloyd, Hao Li, Sarah Fernandes, Daphne Quang, Stephen Johnston, Sarah L Parylak, Xin Jin, Fred H Gage
Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain...
April 16, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29648973/male-and-female-mice-exhibit-divergent-responses-of-the-cortical-vasculature-to-traumatic-brain-injury
#2
Amandine Jullienne, Arjang Salehi, Bethann Affeldt, Mohsen Baghchechi, Elizabeth Haddad, Angela Avitua, Mark Walsworth, Isabelle Enjalric, Mary Hamer, Sonali Bhakta, Jiping Tang, John Zhang, William J Pearce, Andre Obenaus
We previously reported that traumatic brain injuries (TBI) alter cerebrovasculature near the injury site in rats, followed by revascularization over a 2-week period. Here, we tested our hypothesis that male and female adult mice have differential cerebrovascular responses following a moderate controlled cortical impact (CCI). Using in vivo magnetic resonance imaging (MRI), a new technique called vessel painting, and immunohistochemistry, we found no differences between males and females in lesion volume, neurodegeneration, blood-brain barrier (BBB) alteration and microglia activation...
March 5, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29644327/regional-tract-specific-white-matter-hyperintensities-are-associated-with-patterns-to-aging-related-brain-atrophy-via-vascular-risk-factors-but-also-independently
#3
Mohamad Habes, Guray Erus, Jon B Toledo, Nick Bryan, Deborah Janowitz, Jimit Doshi, Henry Völzke, Ulf Schminke, Wolfgang Hoffmann, Hans J Grabe, David A Wolk, Christos Davatzikos
Introduction: We sought to investigate associations of regional white matter hyperintensities (WMHs) within white matter (WM) tracts with cardiovascular risk and brain aging-related atrophy throughout adulthood in the general population, leveraging state of the art pattern analysis methods. Methods: We analyzed a large sample (n = 2367) from the Study of Health in Pomerania, Germany (range 20-90 years). WMHs were automatically segmented on T1-weighted and fluid-attenuated inversion recovery magnetic resonance images, and WMH volumes were calculated in WM regions defined using the John Hopkins University WM tractography atlas...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29625461/allogeneic-ipsc-derived-rpe-cell-graft-failure-following-transplantation-into-the-subretinal-space-in-nonhuman-primates
#4
Trevor J McGill, Jonathan Stoddard, Lauren M Renner, Ilhem Messaoudi, Kapil Bharti, Shoukhrat Mitalipov, Andreas Lauer, David J Wilson, Martha Neuringer
Purpose: To characterize the intraocular immune response following transplantation of iPS-derived allogeneic RPE cells into the subretinal space of non-immune-suppressed rhesus macaques. Methods: GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a two-stage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29543435/a%C3%AE-42-protofibrils-interact-with-and-are-trafficked-through-microglial-derived-microvesicles
#5
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29523925/tspo-pet-with-18-f-ge-180-sensitively-detects-focal-neuroinflammation-in-patients-with-relapsing-remitting-multiple-sclerosis
#6
Marcus Unterrainer, C Mahler, L Vomacka, S Lindner, J Havla, M Brendel, G Böning, B Ertl-Wagner, T Kümpfel, V M Milenkovic, R Rupprecht, M Kerschensteiner, P Bartenstein, Nathalie L Albert
PURPOSE: Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [18 F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [18 F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI)...
March 9, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29518005/pet-imaging-of-microglial-activation-beyond-targeting-tspo
#7
REVIEW
Bieneke Janssen, Danielle J Vugts, Albert D Windhorst, Robert H Mach
Neuroinflammation, which involves microglial activation, is thought to play a key role in the development and progression of neurodegenerative diseases and other brain pathologies. Positron emission tomography is an ideal imaging technique for studying biochemical processes in vivo, and particularly for studying the living brain. Neuroinflammation has been traditionally studied using radiotracers targeting the translocator protein 18 kDa, but this comes with certain limitations. The current review describes alternative biological targets that have gained interest for the imaging of microglial activation over recent years, such as the cannabinoid receptor type 2, cyclooxygenase-2, the P2X₇ receptor and reactive oxygen species, and some promising radiotracers for these targets...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29487876/designing-a-large-field-of-view-two-photon-microscope-using-optical-invariant-analysis
#8
Jonathan R Bumstead, Jasmine J Park, Isaac A Rosen, Andrew W Kraft, Patrick W Wright, Matthew D Reisman, Daniel C Côté, Joseph P Culver
Conventional two-photon microscopy (TPM) is capable of imaging neural dynamics with subcellular resolution, but it is limited to a field-of-view (FOV) diameter [Formula: see text]. Although there has been recent progress in extending the FOV in TPM, a principled design approach for developing large FOV TPM (LF-TPM) with off-the-shelf components has yet to be established. Therefore, we present a design strategy that depends on analyzing the optical invariant of commercially available objectives, relay lenses, mirror scanners, and emission collection systems in isolation...
April 2018: Neurophotonics
https://www.readbyqxmd.com/read/29470968/multiple-sclerosis-mechanisms-and-immunotherapy
#9
REVIEW
Clare Baecher-Allan, Belinda J Kaskow, Howard L Weiner
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system...
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29455391/focal-ischaemic-infarcts-expand-faster-in-cerebellar-cortex-than-cerebral-cortex-in-a-mouse-photothrombotic-stroke-model
#10
Nagarajesh Gorlamandala, Jasneet Parmar, Amanda J Craig, John M Power, Andrew J Moorhouse, Arun V Krishnan, Gary D Housley
It is generally accepted that the cerebellum is particularly vulnerable to ischaemic injury, and this may contribute to the high mortality arising from posterior circulation strokes. However, this has not been systematically examined in an animal model. This study compared the development and resolution of matched photothrombotic microvascular infarcts in the cerebellar and cerebral cortices in adult 129/SvEv mice of both sexes. The photothrombotic lesions were made using tail vein injection of Rose Bengal with a 532 nm laser projected onto a 2 mm diameter aperture over the target region of the brain (with skull thinning)...
February 17, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29428213/nigrostriatal-proteasome-inhibition-impairs-dopamine-neurotransmission-and-motor-function-in-minipigs
#11
Thea P Lillethorup, Andreas N Glud, Aage K O Alstrup, Trine W Mikkelsen, Erik H Nielsen, Hamed Zaer, Doris J Doudet, David J Brooks, Jens Christian H Sørensen, Dariusz Orlowski, Anne M Landau
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We translated this model to the Göttingen minipig by administering lactacystin into the medial forebrain bundle (MFB). Minipigs underwent positron emission tomography (PET) imaging with (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), a marker of vesicular monoamine transporter 2 availability, at baseline and three weeks after the unilateral administration of 100 μg lactacystin into the MFB...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29397529/protein-energy-malnutrition-exacerbates-stroke-induced-forelimb-abnormalities-and-dampens-neuroinflammation
#12
Mariam Alaverdashvili, Sally Caine, Xue Li, Mark J Hackett, Michael P Bradley, Helen Nichol, Phyllis G Paterson
Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke...
February 3, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29335483/pilot-study-to-assess-visualization-and-therapy-of-inflammatory-mechanisms-after-vessel-reopening-in-a-mouse-stroke-model
#13
Ebba Beller, Laura Reuter, Anne Kluge, Christine Preibisch, Ute Lindauer, Alexei Bogdanov, Friederike Lämmer, Claire Delbridge, Kaspar Matiasek, Benedikt J Schwaiger, Tobias Boeckh-Behrens, Claus Zimmer, Alexandra S Gersing
After reperfusion therapy in stroke patients secondary inflammatory processes may increase cerebral damage. In this pilot study, effects of anti-inflammatory therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion-weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted images with and without Bis-5HT-DTPA administration were obtained 24 hours after MCAO...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29238736/combination-of-fluorescent-in-situ-hybridization-fish-and-immunofluorescence-imaging-for-detection-of-cytokine-expression-in-microglia-macrophage-cells
#14
Maria Fe Lanfranco, David J Loane, Italo Mocchetti, Mark P Burns, Sonia Villapol
Microglia and macrophage cells are the primary producers of cytokines in response to neuroinflammatory processes. But these cytokines are also produced by other glial cells, endothelial cells, and neurons. It is essential to identify the cells that produce these cytokines to target their different levels of activation. We used dual RNAscope® fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques to visualize the mRNA expression pattern of pro- and anti-inflammatory cytokines in microglia/macrophages cells...
November 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29201010/microglia-and-brain-plasticity-in-acute-psychosis-and-schizophrenia-illness-course-a-meta-review
#15
REVIEW
Livia J De Picker, Manuel Morrens, Steven A Chance, Delphine Boche
Objective: Schizophrenia poses a tremendous health, social, and economic burden upon patients and society, indicating current treatment options remain inadequate. Recent findings from several lines of evidence have pointed to the importance of immune system involvement in not only premorbid neurodevelopmental but also subsequent symptom generation and aging processes of brain change in schizophrenia. In this meta-review, we use the summarized evidence from recent quantitative systematic reviews (SRs) and meta-analyses of several subspecialties to critically evaluate the hypothesis that immune-related processes shape the symptomatic presentation and illness course of schizophrenia, both directly and indirectly through altered neuroplasticity...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29064155/assessing-inflammation-in-acute-intracerebral-hemorrhage-with-pk11195-pet-and-dynamic-contrast-enhanced-mri
#16
Kamran A Abid, Oluwaseun A Sobowale, Laura M Parkes, Josephine Naish, Geoff J M Parker, Daniel du Plessis, David Brough, Jack Barrington, Stuart M Allan, Rainer Hinz, Adrian R Parry-Jones
BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early-phase development of anti-inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS: Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast-enhanced measurement of blood-brain barrier transfer constant (K(trans) ) and PET with [(11) C]-(R)-PK11195)...
October 24, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29038483/quantitative-microglia-analyses-reveal-diverse-morphologic-responses-in-the-rat-cortex-after-diffuse-brain-injury
#17
Helena Morrison, Kimberly Young, Mahir Qureshi, Rachel K Rowe, Jonathan Lifshitz
Determining regions of altered brain physiology after diffuse brain injury is challenging. Microglia, brain immune cells with ramified and dynamically moving processes, constantly surveil the parenchyma for dysfunction which, when present, results in a changed morphology. Our purpose was to define the spatiotemporal changes in microglia morphology over 28 days following rat midline fluid percussion injury (mFPI) as a first step in exploiting microglia morphology to reflect altered brain physiology. Microglia morphology was quantified from histological sections using Image J skeleton and fractal analysis procedures at three time points and in three regions post-mFPI: impact site, primary somatosensory cortex barrel field (S1BF), and a remote region...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874660/integrative-genomics-of-microglia-implicates-dlg4-psd95-in-the-white-matter-development-of-preterm-infants
#18
Michelle L Krishnan, Juliette Van Steenwinckel, Anne-Laure Schang, Jun Yan, Johanna Arnadottir, Tifenn Le Charpentier, Zsolt Csaba, Pascal Dournaud, Sara Cipriani, Constance Auvynet, Luigi Titomanlio, Julien Pansiot, Gareth Ball, James P Boardman, Andrew J Walley, Alka Saxena, Ghazala Mirza, Bobbi Fleiss, A David Edwards, Enrico Petretto, Pierre Gressens
Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28846081/microglia-turnover-with-aging-and-in-an-alzheimer-s-model-via-long-term-in-vivo-single-cell-imaging
#19
Petra Füger, Jasmin K Hefendehl, Karthik Veeraraghavalu, Ann-Christin Wendeln, Christine Schlosser, Ulrike Obermüller, Bettina M Wegenast-Braun, Jonas J Neher, Peter Martus, Shinichi Kohsaka, Martin Thunemann, Robert Feil, Sangram S Sisodia, Angelos Skodras, Mathias Jucker
To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan...
October 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28836304/impaired-microglia-process-dynamics-post-stroke-are-specific-to-sites-of-secondary-neurodegeneration
#20
Murielle G Kluge, Laura Kracht, Mahmoud Abdolhoseini, Lin Kooi Ong, Sarah J Johnson, Michael Nilsson, Frederick R Walker
Stroke induces tissue death both at the site of infarction and at secondary sites connected to the primary infarction. This latter process has been referred to as secondary neurodegeneration (SND). Using predominantly fixed tissue analyses, microglia have been implicated in regulating the initial response at both damage sites post-stroke. In this study, we used acute slice based multiphoton imaging, to investigate microglia dynamic process movement in mice 14 days after a photothrombotic stroke. We evaluated the baseline motility and process responses to locally induced laser damage in both the peri-infarct (PI) territory and the ipsilateral thalamus, a major site of post-stroke SND...
August 24, 2017: Glia
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