Chronic Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta) with Cisterna Magna Ports: Update on Refinements

2021 ◽  
Author(s):  
David B Gilberto ◽  
Maria S Michener ◽  
Brad E Smith ◽  
Peter J Szczerba ◽  
Marie A Holahan ◽  
...  
Keyword(s):  
Animal Model ◽  
Cerebrospinal Fluid ◽  
Animal Models ◽  
Macaca Mulatta ◽  
Rhesus Macaques ◽  
Implant Design ◽  
Cisterna Magna ◽  
Chronic Models ◽  
New Procedures ◽  
Green Monkeys

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus macaquesusing this approach. Our experience enables us to provide up-to-date information regarding the model, including refinementsto our implant design, reductions in maintenance, and new procedures for dealing with contamination. The results of our experiences have reduced the number of surgeries required and helped to increase the longevity of the implant, with some functioning for more than 18 y. Building on our success in rhesus macaques, we attempted to develop similar animal models in the African green monkeys and dogs but have been unable to develop reliable chronic models for CSF collection in these species.

A Meta-Analysis of Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops), and Ferrets (Mustela putorius furo) as Large Animal Models for COVID-19

2021 ◽  
Author(s):  
Alexandra N Witt ◽  
Rachel D Green ◽  
Andrew N Winterborn
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Macaca Mulatta ◽  
Macaca Fascicularis ◽  
Rhesus Macaques ◽  
Meta Analysis ◽  
Large Animal ◽  
Mustela Putorius ◽  
Cynomolgus Macaques ◽  
Green Monkeys

Animal models are at the forefront of biomedical research for studies of viral transmission, vaccines, and pathogenesis, yetthe need for an ideal large animal model for COVID-19 remains. We used a meta-analysis to evaluate published data relevantto this need. Our literature survey contained 22 studies with data relevant to the incidence of common COVID-19 symptomsin rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), African green monkeys (Chlorocebusaethiops), and ferrets (Mustela putorius furo). Rhesus macaques had leukocytosis on Day 1 after inoculation and pneumonia on Days 7 and 14 after inoculation, in frequencies that were similar enough to humans to reject the null hypothesis of a Fisher exact test. However, the differences in overall presentation of disease were too different from that of humans to successfully identify any of these 4 species as an ideal large animal of COVID-19. The greatest limitation to the current study is a lack of standardization in experimentation and reporting. To expand our understanding of the pathology of COVID-19 and evaluate vaccine immunogenicity, we must extend the unprecedented collaboration that has arisen in the study of COVID-19 to include standardization of animal-based research in an effort to find the optimal animal model.

Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta) naturally infected with simian retrovirus type-D

1990 ◽  
Vol 531 (1-2) ◽  
pp. 148-158 ◽  
Author(s):  
M.P. Heyes ◽  
M. Gravell ◽  
W.T. London ◽  
M. Eckhaus ◽  
J.H. Vickers ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Macaca Mulatta ◽  
Quinolinic Acid ◽  
Rhesus Macaques ◽  
Type D

scholarly journals Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

2020 ◽  
Author(s):  
Fabien Pichon ◽  
Florence Busato ◽  
Simon Jochems ◽  
Beatrice Jacquelin ◽  
Roger Le Grand ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Macaca Mulatta ◽  
Nonhuman Primate ◽  
Rhesus Macaques ◽  
Primate Species ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Green Monkeys ◽  
Nonhuman Primate Species

AbstractThe Infinium Human Methylation450 and Methylation EPIC BeadChips are useful tools for the study of the methylation state of hundreds of thousands of CpG across the human genome at affordable cost. However, in a wide range of experimental settings in particular for studies in infectious or brain-related diseases, human samples cannot be easily obtained. Hence, due to their close developmental, immunological and neurological proximity with humans, non-human primates are used in many research fields of human diseases and for preclinical research. Few studies have used DNA methylation microarrays in simian models. Microarrays designed for the analysis of DNA methylation patterns in the human genome could be useful given the genomic proximity between human and nonhuman primates. However, there is currently information lacking about the specificity and usability of each probe for many nonhuman primate species, including rhesus macaques (Macaca mulatta), originating from Asia, and African green monkeys originating from West-Africa (Chlorocebus sabaeus). Rhesus macaques and African green monkeys are among the major nonhuman primate models utilized in biomedical research. Here, we provide a precise evaluation and re-annotation of the probes of the two microarrays for the analysis of genome-wide DNA methylation patterns in these two Cercopithecidae species. We demonstrate that up to 162,000 of the 450K and 255,000 probes of the EPIC BeadChip can be reliably used in Macaca mulatta or Chlorocebus sabaeus. The annotation files are provided in a format compatible with a variety of preprocessing, normalization and analytical pipelines designed for data analysis from 450K/EPIC arrays, facilitating high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus. They provide the opportunity to the research community to focus their analysis only on those probes identified as reliable. The described analytical workflow leaves the choice to the user to balance coverage versus specificity and can also be applied to other Cercopithecidae species.

scholarly journals Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality

2021 ◽  
Author(s):  
Alyssa C Fears ◽  
Brandon J Beddingfield ◽  
Nicole R Chirichella ◽  
Nadia Slisarenko ◽  
Stephanie Z Killeen ◽  
...  
Keyword(s):  
Macaca Mulatta ◽  
Rhesus Macaques ◽  
Myeloid Cell ◽  
Lung Damage ◽  
Primate Species ◽  
Clinical Onset ◽  
Chlorocebus Aethiops ◽  
Novel Coronavirus ◽  
Species Specific ◽  
Green Monkeys

The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.

scholarly journals ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Teresa Lambe ◽  
Alexandra J. Spencer ◽  
Kelly M. Thomas ◽  
Karen E. Gooch ◽  
Stephen Thomas ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
High Dose ◽  
Lung Pathology ◽  
Virus Shedding ◽  
Immune Profiling ◽  
Careful Assessment

AbstractVaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

Cerebrospinal fluid and serum neopterin and biopterin in D-retrovirus-infected rhesus macaques (Macaca mulatta)

AIDS ◽  
1991 ◽  
Vol 5 (5) ◽  
pp. 555-560 ◽  
Author(s):  
Melvyn P. Heyes ◽  
Andrew Lackner ◽  
Seymour Kaufman ◽  
Sheldon Milstien
Keyword(s):  
Cerebrospinal Fluid ◽  
Macaca Mulatta ◽  
Rhesus Macaques ◽  
Serum Neopterin

scholarly journals ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

2021 ◽  
Author(s):  
Teresa Lambe ◽  
Alexandra Spencer ◽  
Kelly Thomas ◽  
Stephen Thomas ◽  
Andrew White ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Rhesus Macaque ◽  
Clinical Evaluation ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Lung Pathology ◽  
Virus Shedding ◽  
Antibody Titers ◽  
Immune Profiling

Abstract Vaccines against SARS-CoV-2 are urgently required. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titers were boosted by a second dose. Data from these challenge models and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

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