40 results on '"CANET, G"'
Search Results
2. Do surgical expectations change depending on first time surgery or reoperation? A prospective cohort study in lumbar spine surgery
- Author
-
Vilà-Canet, G., Covaro, A., de Frutos, A. García, Ubierna, M. T., Rodríguez-Alabau, S., Mojal, S., and Cáceres, E.
- Published
- 2015
- Full Text
- View/download PDF
3. Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery
- Author
-
de Frutos, AG, Gonzalez-Tartiere, P, Bonet, RC, Garces, MTU, Churruca, AD, Garcia, AR, Adrover, AM, Bru, GS, Velazquez, JJ, Vila-Canet, G, Garcia-Lopez, J, Vives, J, Codinach, M, Rodriguez, L, Granell, JB, and Palou, EC
- Subjects
Clinical trial ,Degenerative spondylolisthesis ,Mesenchymal stromal cells ,TLIF ,Bone graft ,Mesenchymal stem cells ,Spinal fusion ,Tissue engineering ,Lumbar fusion ,Expanded stem cells - Abstract
BACKGROUND CONTEXT: Although autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSE: This study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTING: A prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLE: A total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4-L5 degenerative spondylolisthesis and/or with L4 -L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Spinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODS: Patients who underwent L4-L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTS: Seventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONS: Compared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study. (C) 2020 Elsevier Inc. All rights reserved.
- Published
- 2020
4. Assessing the Psychedelic 'After-Glow' in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
- Author
-
Riba Serrano, Jordi, Sampedro, Frederic, Vilà-Canet, G., de la Fuente Revenga, Mario, Valle, Marta, Roberto, Natalia, Dominguez-Clave, Elisabet, Elices, M., Luna, Luís Eduardo, Crippa, José A. S., Hallak, Jaime E. C., de Araujo, Draulio B., Friedlander, Pablo, Barker, Steven A.., Álvarez, Enrique, Soler, Joaquim, Pascual Mateos, Juan Carlos, Feilding, Amanda, and Universitat Autònoma de Barcelona
- Subjects
Adult ,Male ,Cingulate cortex ,Hallucinogen ,Magnetic Resonance Spectroscopy ,Time Factors ,mindfulness ,Mindfulness ,Glutamic Acid ,Regular Research Articles ,Brain mapping ,Temporal lobe ,03 medical and health sciences ,Imaging, Three-Dimensional ,psychedelic after-effects ,0302 clinical medicine ,Surveys and Questionnaires ,Humans ,magnetic resonance imaging ,Pharmacology (medical) ,human ,Default mode network ,Cerebral Cortex ,Pharmacology ,Aspartic Acid ,Brain Mapping ,Banisteriopsis ,Middle Aged ,Ayahuasca ,Healthy Volunteers ,030227 psychiatry ,Editor's Choice ,Psychiatry and Mental health ,Hallucinogens ,Antidepressant ,Female ,Psychology ,IMAGEM POR RESSONÂNCIA MAGNÉTICA ,Neuroscience ,030217 neurology & neurosurgery ,Follow-Up Studies ,ayahuasca - Abstract
Background Ayahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures. Methods Using 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose. Results Magnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. Conclusions These results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.
- Published
- 2017
5. Thoracolumbar fractures without neurological impairment
- Author
-
Vilà-Canet, G., García de Frutos, A., Covaro, A., Ubierna, M.T., and Caceres, E.
- Subjects
Neurologically Intact Injuries ,Surgical Treatment ,Burst Fracture ,Classification ,Conservative Treatment ,Spine - Abstract
An appropriate protocol and unified management of thoracolumbar fractures without neurological impairment has not been well defined. This review attempts to elucidate some controversies regarding diagnostic tools, the ability to define the most appropriate treatment of classification systems and the evidence for conservative and surgical methods based on the recent literature. Cite this article: Vilà-Canet G, García de Frutos A, Covaro A, Ubierna MT, Caceres E. Thoracolumbar fractures without neurological impairment: a review of diagnosis and treatment. EFORT Open Rev 2016;1:332-338. DOI: 10.1302/2058-5241.1.000029
- Published
- 2016
6. Cell-free cartilage engineering approach using hyaluronic acid-polycaprolactone scaffolds: A study invivo
- Author
-
Lebourg, Myriam Madeleine, Martínez Díaz, S., Garcia Giralt, Natalia, Torres Claramunt, R., Gómez-Tejedor, José Antonio, Gómez Ribelles, José Luís, Vila Canet, G, and Monllau, J.C.
- Subjects
Scaffold ,Materials science ,Polyesters ,Hyaluronic acid ,Biomedical Engineering ,Osteoarthritis ,cell-free PCL scaffold ,Biomaterials ,chemistry.chemical_compound ,Tissue engineering ,hyaluronic acid ,medicine ,Animals ,Cell-free PCL scaffold ,Cell-Free System ,Tissue Scaffolds ,Cartilage ,Biomaterial ,medicine.disease ,osteoarthritis ,medicine.anatomical_structure ,chemistry ,Cartilage regeneration ,tissue engineering ,FISICA APLICADA ,Polycaprolactone ,Thermogravimetry ,MAQUINAS Y MOTORES TERMICOS ,Microscopy, Electron, Scanning ,Bone marrow ,Rabbits ,Biomedical engineering - Abstract
Polycaprolactone scaffolds modified with cross-linked hyaluronic acid were prepared in order to establish whether a more hydrophilic and biomimetic microenvironment benefits the progenitor cells arriving from bone marrow in a cell- free tissue-engineering approach. The polycaprolactone and polycaprolactone/hyaluronic acid scaffolds were characterized in terms of morphology and water absorption capacity. The polycaprolactone and polycaprolactone/hyaluronic acid samples were implanted in a chondral defect in rabbits; bleeding of the subchondral bone was provoked to generate a spontaneous healing response. Repair at 1, 4, 12, and 24 weeks was assessed macroscopically using the International Cartilage Repair Society score and the Oswestry Arthroscopy Score and microscopically using immunohistological staining for collagen type I and type II, and for Ki-67. The presence of hyaluronic acid improves scaffold performance, which supports a good repair response without biomaterial pre-seeding., JLGR, JAGT and JCM acknowledge the support of the Spanish Ministry of Science through projects No. MAT2010-21611-C03-01 and -02. The support of Grant 2005SGR 00762 and 2005SGR 00848 (Catalan Department of Universities, Research and the Information Society) and the Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RETICEF) is also acknowledged. Myriam Lebourg acknowledges funding from UPV through the PAID-10 project funds and from CIBER-BBN. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.
- Published
- 2014
7. Cell-free cartilage engineering approach using hyaluronic acid-polycaprolactone scaffolds: A study invivo
- Author
-
Universitat Politècnica de València. Centro de Biomateriales e Ingeniería Tisular - Centre de Biomaterials i Enginyeria Tissular, Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería del Diseño - Escola Tècnica Superior d'Enginyeria del Disseny, Ministerio de Ciencia e Innovación, Generalitat de Catalunya, Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad, Universitat Politècnica de València, Instituto de Salud Carlos III, European Regional Development Fund, Lebourg, Myriam Madeleine, Martínez Díaz, S., Garcia Giralt, Natalia, Torres Claramunt, R., Gómez-Tejedor, José Antonio, Gómez Ribelles, José Luís, Vila Canet, G, Monllau, J.C., Universitat Politècnica de València. Centro de Biomateriales e Ingeniería Tisular - Centre de Biomaterials i Enginyeria Tissular, Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials, Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería del Diseño - Escola Tècnica Superior d'Enginyeria del Disseny, Ministerio de Ciencia e Innovación, Generalitat de Catalunya, Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad, Universitat Politècnica de València, Instituto de Salud Carlos III, European Regional Development Fund, Lebourg, Myriam Madeleine, Martínez Díaz, S., Garcia Giralt, Natalia, Torres Claramunt, R., Gómez-Tejedor, José Antonio, Gómez Ribelles, José Luís, Vila Canet, G, and Monllau, J.C.
- Abstract
Polycaprolactone scaffolds modified with cross-linked hyaluronic acid were prepared in order to establish whether a more hydrophilic and biomimetic microenvironment benefits the progenitor cells arriving from bone marrow in a cell- free tissue-engineering approach. The polycaprolactone and polycaprolactone/hyaluronic acid scaffolds were characterized in terms of morphology and water absorption capacity. The polycaprolactone and polycaprolactone/hyaluronic acid samples were implanted in a chondral defect in rabbits; bleeding of the subchondral bone was provoked to generate a spontaneous healing response. Repair at 1, 4, 12, and 24 weeks was assessed macroscopically using the International Cartilage Repair Society score and the Oswestry Arthroscopy Score and microscopically using immunohistological staining for collagen type I and type II, and for Ki-67. The presence of hyaluronic acid improves scaffold performance, which supports a good repair response without biomaterial pre-seeding.
- Published
- 2014
8. Cell-free cartilage engineering approach using hyaluronic acid–polycaprolactone scaffolds: A study in vivo
- Author
-
Lebourg, M, primary, Martínez-Díaz, S, additional, García-Giralt, N, additional, Torres-Claramunt, R, additional, Ribelles, JL Gómez, additional, Vila-Canet, G, additional, and Monllau, JC, additional
- Published
- 2013
- Full Text
- View/download PDF
9. CORRESPONDENCE. THE FORCES AND STRAINS OF RECOILS.
- Author
-
DAVEY, H, BUTTER, H J, JENKIN, F, CANET, G, POLES, W, GREENHILL, A G, and BASHWORTH, F
- Published
- 1882
- Full Text
- View/download PDF
10. Théorie des freins hydrauliques : description des freins des systèmes Krupp, Rendel et Wasseur
- Author
-
Canet, G and Canet, G
- Abstract
Al final del texto: "Extrait de la Revue d'artillerie"
11. Towards the automatic verification of PLC programs written in Instruction List
- Author
-
Canet, G., primary, Couffin, S., additional, Lesage, J.-J., additional, Petit, A., additional, and Schnoebelen, P., additional
- Full Text
- View/download PDF
12. A Value Analysis for C Programs.
- Author
-
Canet, G., Cuoq, P., and Monate, B.
- Published
- 2009
- Full Text
- View/download PDF
13. Towards the automatic verification of PLC programs written in Instruction List.
- Author
-
Canet, G., Couffin, S., Lesage, J.-J., Petit, A., and Schnoebelen, P.
- Published
- 2000
- Full Text
- View/download PDF
14. Mapa de los Paisajes de Cuba por Gerardo Canet com la colaboracion de Erwin Raisz. (inset) La Habana y sus alrededores.
- Author
-
Raisz, Erwin and Canet, Gerardo
- Subjects
Pictorial map ,Physical - Abstract
Relief shown in shaded relief with hachures and pictorial enhancements. Small illustration and brief textual description of various regions. In Spanish. Taken from the Atlas de Cuba by Canet and Raisz, 1949
- Published
- 1949
15. The Absence of Funeral Rites as a Risk Factor for the French Bereaved Population.
- Author
-
Sani L, Cape C, Merheb J, Poulin N, Lassagne B, Canet G, Lallemant M, Cherblanc J, De Vincenzo C, Testoni I, Canellopoulos L, Kaufmann NT, and Bacqué MF
- Abstract
During the COVID-19 pandemic, stringent measures were imposed in numerous countries, including France. These measures significantly disrupted societal practices, particularly mourning and funeral rituals. This study, conducted between June and September 2021 as part of the COVIDEUIL-France research, involved 242 participants, predominantly female (84%) with an average age of 49.64 years. The research aimed to investigate the consequences of the absence of funeral rituals and the adoption of personalized, domestic, and digital alternatives. Using online surveys and psychological tools, including the Traumatic Grief Inventory Self Report Version (TGI-SR), General Health Questionnaire-28 (GHQ-28), and Post-traumatic Growth Inventory (PTGI), the study found a significant correlation between the lack of traditional practices and grief complications. Despite 21.81% of participants compensating with personal commemorations, digital commemorations were underutilized, raising questions about their effectiveness. The study provides crucial insights, emphasizing the need to address the psychological effects of disrupted mourning practices in France., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
16. Beneficial effects of miR-132/212 deficiency in the zQ175 mouse model of Huntington's disease.
- Author
-
Nateghi B, Keraudren R, Boulay G, Bazin M, Goupil C, Canet G, Loiselle A, St-Amour I, Planel E, Soulet D, and Hébert SS
- Abstract
Huntington's disease (HD) is a rare genetic neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. One hypothesis suggests that the mutant HTT gene contributes to HD neuropathology through transcriptional dysregulation involving microRNAs (miRNAs). In particular, the miR-132/212 cluster is strongly diminished in the HD brain. This study explores the effects of miR-132/212 deficiency specifically in adult HD zQ175 mice. The absence of miR-132/212 did not impact body weight, body temperature, or survival rates. Surprisingly, miR-132/212 loss seemed to alleviate, in part, the effects on endogenous Htt expression, HTT inclusions, and neuronal integrity in HD zQ175 mice. Additionally, miR-132/212 depletion led to age-dependent improvements in certain motor functions. Transcriptomic analysis revealed alterations in HD-related networks in WT- and HD zQ175-miR-132/212-deficient mice, including significant overlap in BDNF and Creb1 signaling pathways. Interestingly, however, a higher number of miR-132/212 gene targets was observed in HD zQ175 mice lacking the miR-132/212 cluster, especially in the striatum. These findings suggest a nuanced interplay between miR-132/212 expression and HD pathogenesis, providing potential insights into therapeutic interventions. Further investigation is needed to fully understand the underlying mechanisms and therapeutic potential of modulating miR-132/212 expression during HD progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nateghi, Keraudren, Boulay, Bazin, Goupil, Canet, Loiselle, St-Amour, Planel, Soulet and Hébert.)
- Published
- 2024
- Full Text
- View/download PDF
17. Age-dependent impact of streptozotocin on metabolic endpoints and Alzheimer's disease pathologies in 3xTg-AD mice.
- Author
-
Canet G, Gratuze M, Zussy C, Bouali ML, Diaz SD, Rocaboy E, Laliberté F, El Khoury NB, Tremblay C, Morin F, Calon F, Hébert SS, Julien C, and Planel E
- Subjects
- Animals, Mice, Disease Models, Animal, Insulin metabolism, Aging metabolism, Male, Age Factors, Phosphorylation, Brain metabolism, Brain pathology, Alzheimer Disease metabolism, Alzheimer Disease pathology, Alzheimer Disease genetics, Mice, Transgenic, Streptozocin, tau Proteins metabolism, Amyloid beta-Peptides metabolism
- Abstract
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with a complex origin, thought to involve a combination of genetic, biological and environmental factors. Insulin dysfunction has emerged as a potential factor contributing to AD pathogenesis, particularly in individuals with diabetes, and among those with insulin deficiency or undergoing insulin therapy. The intraperitoneal administration of streptozotocin (STZ) is widely used in rodent models to explore the impact of insulin deficiency on AD pathology, although prior research predominantly focused on young animals, with no comparative analysis across different age groups. Our study aimed to fill this gap by analyzing the impact of insulin dysfunction in 7 and 23 months 3xTg-AD mice, that exhibit both amyloid and tau pathologies. Our objective was to elucidate the age-specific consequences of insulin deficiency on AD pathology. STZ administration led to insulin deficiency in the younger mice, resulting in an increase in cortical amyloid-β (Aβ) and tau aggregation, while tau phosphorylation was not significantly affected. Conversely, older mice displayed an unexpected resilience to the peripheral metabolic impact of STZ, while exhibiting an increase in both tau phosphorylation and aggregation without significantly affecting amyloid pathology. These changes were paralleled with alterations in signaling pathways involving tau kinases and phosphatases. Several markers of blood-brain barrier (BBB) integrity declined with age in 3xTg-AD mice, which might have facilitated a direct neurotoxic effect of STZ in older mice. Overall, our research confirms the influence of insulin signaling dysfunction on AD pathology, but also advises careful interpretation of data related to STZ-induced effects in older animals., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
18. Sleep-wake body temperature regulates tau secretion in mice and correlates with CSF and plasma tau in humans.
- Author
-
Canet G, Monteiro FDG, Rocaboy E, Diego-Diaz S, Khelaifia B, Kim J, Valencia D, Yin A, Wu HT, Howell J, Blank E, Laliberté F, Fortin N, Boscher E, Fereydouni-Forouzandeh P, Champagne S, Guisle I, Hébert S, Pernet V, Liu H, Lu W, Debure L, Rapoport D, Ayappa I, Varga A, Parekh A, Osorio R, Lacroix S, Lucey B, Blessing E, and Planel E
- Abstract
The sleep-wake cycle regulates interstitial fluid and cerebrospinal fluid (CSF) tau levels in both mouse and human by mechanisms that remain unestablished. Here, we reveal a novel pathway by which wakefulness increases extracellular tau levels in mouse and humans. In mice, higher body temperature (BT) associated with wakefulness and sleep deprivation increased CSF tau. In vitro , wakefulness temperatures upregulated tau secretion via a temperature-dependent increase in activity and expression of unconventional protein secretion pathway-1 components, namely caspase-3-mediated C-terminal cleavage of tau (TauC3), and membrane expression of PIP
2 and syndecan-3. In humans, the increase in both CSF and plasma tau levels observed post-wakefulness correlated with BT increase during wakefulness. Our findings suggest sleep-wake variation in BT may contribute to regulating extracellular tau levels, highlighting the importance of thermoregulation in pathways linking sleep disturbance to neurodegeneration, and the potential for thermal intervention to prevent or delay tau-mediated neurodegeneration., Competing Interests: Competing interests: All authors declare no competing interests.- Published
- 2024
- Full Text
- View/download PDF
19. Western Blot of Tau Protein from Mouse Brains Extracts: How to Avoid Signal Artifacts.
- Author
-
Fereydouni-Forouzandeh P, Canet G, Diego-Diàz S, Rocaboy E, Petry S, Whittington RA, and Planel E
- Subjects
- Mice, Animals, Humans, tau Proteins metabolism, Artifacts, Phosphorylation, Mice, Transgenic, Mice, Knockout, Epitopes metabolism, Brain metabolism, Blotting, Western, Tauopathies metabolism, Alzheimer Disease metabolism
- Abstract
Tau is a microtubule-associated protein enriched in the axonal compartment. Its most well-known function is to bind and stabilize microtubules. In Alzheimer's disease and other neurodegenerative diseases known as tauopathies, tau undergoes several abnormal post-translational modifications including hyperphosphorylation, conformational changes, oligomerization, and aggregation. Numerous mouse models of tauopathies have been developed, and Western blotting remains an invaluable tool in studying tau protein physiological and pathological changes in these models. However, many of the antibodies that have been developed to analyze tau post-translational modifications are mouse monoclonal, which are at risk of producing artifactual signals in Western blotting procedures. This risk does not arise due to their lack of specificity, but rather because the secondary antibodies used to detect them will also react with the heavy chain of endogenous mouse immunoglobulins (Igs), leading to a non-specific signal at the same molecular weight as tau protein (around 50 kDa). Here, we present the use of anti-light-chain secondary antibodies as a simple and efficient technique to prevent non-specific Ig signals around 50 kDa. We demonstrate the efficacy of this method by either eliminating or identifying artifactual signals when using monoclonal antibodies directed at non-phosphorylated epitopes (T49, Tau3R, Tau4R), phosphorylated epitopes (MC6, AT180, CP13), or an abnormal tau conformation (MC1), in wild-type (WT) mice with tau hyperphosphorylation (hypothermic), transgenic mice overexpressing human tau (hTau mice), and tau knockout (TKO) mice., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
20. Methods for Biochemical Isolation of Insoluble Tau in Rodent Models of Tauopathies.
- Author
-
Canet G, Rocaboy E, Diego-Diàz S, Whittington RA, Julien C, and Planel E
- Subjects
- Mice, Animals, Rodentia metabolism, Disease Models, Animal, tau Proteins genetics, tau Proteins metabolism, Mice, Transgenic, Brain metabolism, Tauopathies metabolism, Alzheimer Disease metabolism
- Abstract
The intracellular accumulation of microtubule-associated protein tau is a characteristic feature of tauopathies, a group of neurodegenerative diseases including Alzheimer's disease. Formation of insoluble tau aggregates is initiated by the abnormal hyperphosphorylation and oligomerization of tau. Over the past decades, multiple transgenic rodent models mimicking tauopathies have been develop, showcasing this neuropathological hallmark. The biochemical analysis of insoluble tau in these models has served as a valuable tool to understand the progression of tau-related pathology. In this chapter, we provide a comprehensive review of the two primary methods for isolating insoluble tau, namely, sarkosyl and formic acid extraction (and their variants), which are employed for biochemical analysis in transgenic mouse models of tauopathy. We also analyze the strengths and limitations of these methods., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
21. Temperature-induced Artifacts in Tau Phosphorylation: Implications for Reliable Alzheimer's Disease Research.
- Author
-
Canet G, Rocaboy E, Laliberté F, Boscher E, Guisle I, Diego-Diaz S, Fereydouni-Forouzandeh P, Whittington RA, Hébert SS, Pernet V, and Planel E
- Abstract
In preclinical research on Alzheimer's disease and related tauopathies, tau phosphorylation analysis is routinely employed in both cellular and animal models. However, recognizing the sensitivity of tau phosphorylation to various extrinsic factors, notably temperature, is vital for experimental accuracy. Hypothermia can trigger tau hyperphosphorylation, while hyperthermia leads to its dephosphorylation. Nevertheless, the rapidity of tau phosphorylation in response to unintentional temperature variations remains unknown. In cell cultures, the most significant temperature change occurs when the cells are removed from the incubator before harvesting, and in animal models, during anesthesia prior to euthanasia. In this study, we investigate the kinetics of tau phosphorylation in N2a and SH-SY5Y neuronal cell lines, as well as in mice exposed to anesthesia. We observed changes in tau phosphorylation within the few seconds upon transferring cell cultures from their 37°C incubator to room temperature conditions. However, cells placed directly on ice post-incubation exhibited negligible phosphorylation changes. In vivo, isoflurane anesthesia rapidly resulted in tau hyperphosphorylation within the few seconds needed to lose the pedal withdrawal reflex in mice. These findings emphasize the critical importance of preventing temperature variation in researches focused on tau. To ensure accurate results, we recommend avoiding anesthesia before euthanasia and promptly placing cells on ice after removal from the incubator. By controlling temperature fluctuations, the reliability and validity of tau phosphorylation studies can be significantly enhanced.
- Published
- 2023
- Full Text
- View/download PDF
22. Superiority of the Triple-Acting 5-HT 6 R/5-HT 3 R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT 6 R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats.
- Author
-
Grychowska K, López-Sánchez U, Vitalis M, Canet G, Satała G, Olejarz-Maciej A, Gołębiowska J, Kurczab R, Pietruś W, Kubacka M, Moreau C, Walczak M, Blicharz-Futera K, Bento O, Bantreil X, Subra G, Bojarski AJ, Lamaty F, Becamel C, Zussy C, Chaumont-Dubel S, Popik P, Nury H, Marin P, Givalois L, and Zajdel P
- Subjects
- Rats, Animals, Cryoelectron Microscopy, Receptors, Serotonin, Serotonin Antagonists pharmacology, Serotonin Antagonists therapeutic use, Monoamine Oxidase, Cognition, Monoamine Oxidase Inhibitors pharmacology, Monoamine Oxidase Inhibitors therapeutic use, Serotonin adverse effects, Alzheimer Disease drug therapy, Alzheimer Disease chemically induced
- Abstract
The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HT
6 R antagonism and interaction with 5-HT3 R were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable PZ-1922 reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HT6 R antagonist) in the AD model, which involved intracerebroventricular injection of an oligomeric solution of amyloid-β peptide (oAβ) in the T-maze test in rats. PZ-1922 , but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAβ. These data support the potential of a multitarget approach involving the joint modulation of 5-HT6 R/5-HT3 R/MAO-B in AD.- Published
- 2023
- Full Text
- View/download PDF
23. Influence on Therapeutic Decision-Making of Supine and Standing Radiographs after Traumatic Thoracolumbar Fracture in the Elderly.
- Author
-
Noguera-Alonso L, Vilà-Canet G, De Caso-Rodriguez J, Da Ponte-Prieto A, Perez-Romera AB, and Velazquez-Fragoso JJ
- Subjects
- Female, Humans, Aged, Male, Supine Position, Radiography, Tomography, X-Ray Computed, Standing Position, Spine
- Abstract
Background: A standing X-ray is recommended for decision-making relative to the therapy for a traumatic thoracolumbar fracture (TLF). However, standing X-ray management can be demanding in elderly patients because of pain. The goal of this study was to determine whether supine radiograph is sufficient for proper therapeutic decision-making in patients older than 65 years with acute stable traumatic TLF., Methods: Patients older than 65 years who came to the emergency department diagnosed with an acute and stable traumatic vertebral fracture between T10 and L3 (both included) were included in the study. Initially, all the patients were studied with a supine radiograph and computed tomography (CT) scan. If the TLF was stable, a standing radiograph was performed. Segmental kyphosis (SK) and visual analog scale (VAS) score were collected and compared in both the supine and standing X-ray projections., Results: Twenty-seven patients with a mean age of 76.39 (range: 65-93) years were included; most were females. The mean supine SK was 10.14degrees (SD±7.22degrees). It increased to 12.97 (SD±8.61degrees) in the standing projection ( p <0.001). In 37.1% of the patients, the SK increased from 13.22degrees (SD±7.21degrees) in supine X-ray to 19.96degrees (SD±5.34degrees) in the standing position in this group. When the initial supine projection showed an SK of ≥10degrees, the mean SK observed in the standing X-ray increased to 20.5degrees (SD±5.30, p =0.321)., Conclusion: Stable traumatic TLF in patients older than 65 years showing ≥10degrees of SK in supine radiography may benefit from a standing radiography to make a proper therapeutic decision., Competing Interests: None declared., (Thieme. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
24. The pathomimetic oAβ 25 - 35 model of Alzheimer's disease: Potential for screening of new therapeutic agents.
- Author
-
Canet G, Zussy C, Hernandez C, Maurice T, Desrumaux C, and Givalois L
- Subjects
- Animals, Humans, Aged, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System metabolism, Pituitary-Adrenal System pathology, Amyloid beta-Peptides metabolism, tau Proteins metabolism, Oxidative Stress, Alzheimer Disease genetics
- Abstract
Alzheimer's disease (AD) is the most common form of dementia in the elderly, currently affecting more than 40 million people worldwide. The two main histopathological hallmarks of AD were identified in the 1980s: senile plaques (composed of aggregated amyloid-β (Aβ) peptides) and neurofibrillary tangles (composed of hyperphosphorylated tau protein). In the human brain, both Aβ and tau show aggregation into soluble and insoluble oligomers. Soluble oligomers of Aβ include their most predominant forms - Aβ
1 - 40 and Aβ1 - 42 - as well as shorter peptides such as Aβ25 - 35 or Aβ25 - 35/40 . Most animal models of AD have been developed using transgenesis, based on identified human mutations. However, these familial forms of AD represent less than 1% of AD cases. In this context, the idea emerged in the 1990s to directly inject the Aβ25 - 35 fragment into the rodent brain to develop an acute model of AD that could mimic the disease's sporadic forms (99% of all cases). This review aims to: (1) summarize the biological activity of Aβ25 - 35 , focusing on its impact on the main structural and functional alterations observed in AD (cognitive deficits, APP misprocessing, tau system dysfunction, neuroinflammation, oxidative stress, cholinergic and glutamatergic alterations, HPA axis dysregulation, synaptic deficits and cell death); and (2) confirm the interest of this pathomimetic model in AD research, as it has helped identify and characterize many molecules (marketed, in clinical development, and in preclinical testing), and to the development of alternative approaches for AD prevention and therapy. Today, the Aβ25 - 35 model appears as a first-intent choice model to rapidly screen the symptomatic or neuroprotective potencies of new compounds, chemical series, or innovative therapeutic strategies., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
25. Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia.
- Author
-
Guisle I, Canet G, Pétry S, Fereydouni-Forouzandeh P, Morin F, Kérauden R, Whittington RA, Calon F, Hébert SS, and Planel E
- Subjects
- Animals, Menthol, Mice, Phosphorylation, Prospective Studies, tau Proteins metabolism, Alzheimer Disease pathology, Steam Bath, Tauopathies pathology
- Abstract
In Alzheimer's disease (AD), hyper-phosphorylation and aggregation of tau correlate with clinical progression and represent a valid therapeutic target. A recent 20-year prospective study revealed an association between moderate to high frequency of Finnish sauna bathing and a lower incidence of dementia and AD, but the molecular mechanisms underlying these benefits remain uncertain. Here, we tested the hypothesis that sauna-like conditions could lower tau phosphorylation by increasing body temperature. We observed a decrease in tau phosphorylation in wild-type and hTau mice as well as in neuron-like cells when exposed to higher temperatures. These effects were correlated with specific changes in phosphatase and kinase activities, but not with inflammatory or heat shock responses. We also used a drug strategy to promote thermogenesis: topical application of menthol, which led to a sustained increase in body temperature in hTau mice, concomitant with a significant decrease in tau phosphorylation. Our results suggest that sauna-like conditions or menthol treatment could lower tau pathology through mild hyperthermia, and may provide promising therapeutic strategies for AD and other tauopathies., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
26. Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease.
- Author
-
Zussy C, John R, Urgin T, Otaegui L, Vigor C, Acar N, Canet G, Vitalis M, Morin F, Planel E, Oger C, Durand T, Rajshree SL, Givalois L, Devarajan PV, and Desrumaux C
- Abstract
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 n -3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain. Several studies have reported reduced brain DHA concentrations in Alzheimer's disease (AD) patients' brains. Although a number of epidemiological studies suggest that dietary DHA consumption may protect the elderly from developing cognitive impairment or dementia including AD, several review articles report an inconclusive association between omega-3 PUFAs intake and cognitive decline. The source of these inconsistencies might be because DHA is highly oxidizable and its accessibility to the brain is limited by the blood-brain barrier. Thus, there is a pressing need for new strategies to improve DHA brain supply. In the present study, we show for the first time that the intranasal administration of nanovectorized DHA reduces Tau phosphorylation and restores cognitive functions in two complementary murine models of AD. These results pave the way for the development of a new approach to target the brain with DHA for the prevention or treatment of this devastating disease.
- Published
- 2022
- Full Text
- View/download PDF
27. Seizure activity triggers tau hyperphosphorylation and amyloidogenic pathways.
- Author
-
Canet G, Zub E, Zussy C, Hernandez C, Blaquiere M, Garcia V, Vitalis M, deBock F, Moreno-Montano M, Audinat E, Desrumaux C, Planel E, Givalois L, and Marchi N
- Subjects
- Amyloid Precursor Protein Secretases metabolism, Animals, Aspartic Acid Endopeptidases metabolism, Disease Models, Animal, Hippocampus pathology, Inflammation metabolism, Kainic Acid toxicity, Mice, Mice, Inbred C57BL, Seizures, Epilepsy, Temporal Lobe, Status Epilepticus
- Abstract
Objective: Although epilepsies and neurodegenerative disorders show pathophysiological similarities, their direct functional associations are unclear. Here, we tested the hypothesis that experimental seizures can induce tau hyperphosphorylation and amyloidogenic modifications over time, with intersections with neuroinflammation., Methods: We used a model of mesial temporal lobe epilepsy (MTLE) where unilateral intrahippocampal injection of kainic acid (KA) in C57BL/6 mice elicits epileptogenesis and spontaneous focal seizures. We used a model of generalized status epilepticus (SE) obtained by intraperitoneal KA injection in C57BL/6 mice. We performed analyses and cross-comparisons according to a schedule of 72 h, 1 week, and 8 weeks after KA injection., Results: In experimental MTLE, we show AT100, PHF1, and CP13 tau hyperphosphorylation during epileptogenesis (72 h-1 week) and long-term (8 weeks) during spontaneous seizures in the ipsilateral hippocampi, the epileptogenic zone. These pathological modifications extended to the contralateral hippocampus, a seizure propagating zone with no histological lesion or sclerosis. Two kinases, Cdk5 and GSK3β, implicated in the pathological phosphorylation of tau, were activated. In this MTLE model, the induction of the amyloidogenic pathway (APP, C99, BACE1) was prominent and long-lasting in the epileptogenic zone. These Alzheimer's disease (AD)-relevant markers, established during seizure progression and recurrence, reciprocated an enduring glial (GFAP, Iba1) inflammation and the inadequate activation of the endogenous, anti-inflammatory, glucocorticoid receptor system. By contrast, a generalized SE episode provoked a predominantly transient induction of tau hyperphosphorylation and amyloidogenic markers in the hippocampus, along with resolving inflammation. Finally, we identified overlapping profiles of long-term hippocampal tau hyperphosphorylation by comparing MTLE to J20 mice, the latter a model relevant to AD., Significance: MTLE and a generalized SE prompt persistent and varying tau hyperphosphorylation or amyloidogenic modifications in the hippocampus. In MTLE, an AD-relevant molecular trajectory intertwines with neuroinflammation, spatiotemporally involving epileptogenic and nonlesional seizure propagating zones., (© 2022 International League Against Epilepsy.)
- Published
- 2022
- Full Text
- View/download PDF
28. Chronic Glucocorticoids Consumption Triggers and Worsens Experimental Alzheimer's Disease-Like Pathology by Detrimental Immune Modulations.
- Author
-
Canet G, Zussy C, Hernandez C, Chevallier N, Marchi N, Desrumaux C, and Givalois L
- Subjects
- Animals, Corticosterone, Disease Models, Animal, Glucocorticoids metabolism, Glucocorticoids toxicity, Hippocampus metabolism, Mice, Mice, Transgenic, Rats, Receptors, Glucocorticoid metabolism, tau Proteins metabolism, Alzheimer Disease metabolism, Drinking Water
- Abstract
Introduction: Among the risk factors identified in the sporadic forms of Alzheimer's disease (AD), environmental and lifestyle elements are of growing interest. Clinical observations suggest that stressful events can anticipate AD onset, while stress-related disorders can promote AD. Here, we tested the hypothesis that a chronic treatment with glucocorticoids is sufficient to trigger or exacerbate AD molecular hallmarks., Methods: We first validated a rat model of experimental chronic glucocorticoids (GC) consumption (corticosterone [CORT] in drinking water for 4 weeks). Then, to evaluate the consequences of chronic GC consumption on the onset of amyloid-β (Aβ) toxicity, animals chronically treated with GC were intracerebroventricularly injected with an oligomeric solution of Aβ25-35 (oAβ) (acute model of AD). We evaluated AD-related cognitive deficits and pathogenic mechanisms, with a special emphasis on neuroinflammatory markers., Results: Chronic CORT consumption caused the inhibition of the nonamyloidogenic pathways, the impairment of Aβ clearance processes and the induction of amyloidogenic pathways in the hippocampus. The principal enzymes involved in glucocorticoid receptor activation and Tau phosphorylation were upregulated. Importantly, the AD-like phenotype triggered by chronic CORT was analogous to the one caused by oAβ. These molecular commonalities across models were independent from inflammation, as chronic CORT was immunosuppressive while oAβ was pro-inflammatory. When chronic CORT consumption anticipated the induction of the oAβ pathology, we found a potentiation of neuroinflammatory processes associated with an exacerbation of synaptic and memory deficits but also an aggravation of AD-related hallmarks., Discussion/conclusion: This study unravels new functional outcomes identifying chronic CORT consumption as a main risk factor for AD and suggests that glucocorticoid-based therapies should be prescribed with caution in populations with AD risk., (© 2021 S. Karger AG, Basel.)
- Published
- 2022
- Full Text
- View/download PDF
29. Elective Lumbar Spine Surgery in Depressed Patients: Is it Worth it?
- Author
-
Vilà-Canet G, Covaro A, Isart A, Cáncer D, Ciccolo F, de Frutos AG, Ubierna M, and Cáceres E
- Abstract
Background: The objective of this study is to compare surgical results (pain, function, and satisfaction) between a group of depressed patients and a nondepressed group who had been operated on for a degenerative lumbar condition., Methods: Prospective observational study. Preoperative pain (lumbar and radicular visual analog scale [VAS]), function (Oswestry Disability Index [ODI]), and depression (Zung depression scale) data were collected in patients listed to be operated on for a lumbar degenerative condition. One year postoperatively, ODI and VAS data were collected again as well as a satisfaction question (are you satisfied with the surgical results? Yes/no)., Results: Ninety-seven patients were included in the study, 78 nondepressed patients (80.4%) and 19 depressed patients (19.6%). Preoperatively, depressed patients had more lumbar pain ( P = .00) and more functional limitation ( P = .01) than nondepressed patients. One year postoperatively, depressed patients had more radicular pain ( P = .029) and more functional limitation ( P = .03) than non-depressed patients. The overall improvement of pain and function was similar between both groups (not significant). Seventy percent of depressed patients and 80% of nondepressed patients were satisfied with the surgical outcome ( P = .52) 1 year postoperatively., Conclusion: Depressed patients experience the same overall level of improvement as nondepressed patients, despite having more pain and functional limitation preoperatively and 1 year after elective lumbar spine surgery than nondepressed patients. The level of satisfaction does not differ significantly between the two groups., Level of Evidence: 2., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS.)
- Published
- 2021
- Full Text
- View/download PDF
30. Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery.
- Author
-
García de Frutos A, González-Tartière P, Coll Bonet R, Ubierna Garcés MT, Del Arco Churruca A, Rivas García A, Matamalas Adrover A, Saló Bru G, Velazquez JJ, Vila-Canet G, García-Lopez J, Vives J, Codinach M, Rodriguez L, Bagó Granell J, and Càceres Palou E
- Subjects
- Bone Marrow, Humans, Ilium, Lumbar Vertebrae diagnostic imaging, Lumbar Vertebrae surgery, Prospective Studies, Quality of Life, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, Spinal Fusion adverse effects
- Abstract
Background Context: Although autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs., Purpose: This study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy., Study Design/setting: A prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial., Patient Sample: A total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4-L5 degenerative spondylolisthesis and/or with L4-L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF)., Outcome Measures: Spinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment., Methods: Patients who underwent L4-L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups., Results: Seventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups., Conclusions: Compared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
31. Glucocorticoid receptors signaling impairment potentiates amyloid-β oligomers-induced pathology in an acute model of Alzheimer's disease.
- Author
-
Canet G, Pineau F, Zussy C, Hernandez C, Hunt H, Chevallier N, Perrier V, Torrent J, Belanoff JK, Meijer OC, Desrumaux C, and Givalois L
- Subjects
- Adrenal Cortex Hormones chemistry, Amyloid beta-Protein Precursor metabolism, Animals, Behavior, Animal, Disease Models, Animal, Glucocorticoids metabolism, Homeostasis, Hypothalamo-Hypophyseal System, Male, Phosphorylation, Pituitary-Adrenal System, Rats, Rats, Sprague-Dawley, Signal Transduction, Alzheimer Disease metabolism, Amyloid beta-Peptides chemistry, Receptors, Glucocorticoid metabolism, tau Proteins metabolism
- Abstract
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis occurs early in Alzheimer's disease (AD), associated with elevated circulating glucocorticoids (GC) and glucocorticoid receptors (GR) signaling impairment. However, the precise role of GR in the pathophysiology of AD remains unclear. Using an acute model of AD induced by the intracerebroventricular injection of amyloid-β oligomers (oAβ), we analyzed cellular and behavioral hallmarks of AD, GR signaling pathways, processing of amyloid precursor protein, and enzymes involved in Tau phosphorylation. We focused on the prefrontal cortex (PFC), particularly rich in GR, early altered in AD and involved in HPA axis control and cognitive functions. We found that oAβ impaired cognitive and emotional behaviors, increased plasma GC levels, synaptic deficits, apoptosis and neuroinflammatory processes. Moreover, oAβ potentiated the amyloidogenic pathway and enzymes involved both in Tau hyperphosphorylation and GR activation. Treatment with a selective GR modulator (sGRm) normalized plasma GC levels and all behavioral and biochemical parameters analyzed. GR seems to occupy a central position in the pathophysiology of AD. Deregulation of the HPA axis and a feed-forward effect on PFC GR sensitivity could participate in the etiology of AD, in perturbing Aβ and Tau homeostasis. These results also reinforce the therapeutic potential of sGRm in AD., (© 2019 Federation of American Societies for Experimental Biology.)
- Published
- 2020
- Full Text
- View/download PDF
32. The GR-ANXA1 pathway is a pathological player and a candidate target in epilepsy.
- Author
-
Zub E, Canet G, Garbelli R, Blaquiere M, Rossini L, Pastori C, Sheikh M, Reutelingsperger C, Klement W, de Bock F, Audinat E, Givalois L, Solito E, and Marchi N
- Subjects
- Animals, Annexin A1 genetics, Blood Cell Count, Brain drug effects, Brain metabolism, Corticosterone metabolism, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, Hippocampus, Humans, Inflammation metabolism, Inflammation pathology, Kainic Acid administration & dosage, Kainic Acid pharmacology, Mice, Mice, Inbred C57BL, Receptors, Glucocorticoid genetics, Annexin A1 metabolism, Epilepsy, Receptors, Glucocorticoid metabolism
- Abstract
Immune changes occur in experimental and clinical epilepsy. Here, we tested the hypothesis that during epileptogenesis and spontaneous recurrent seizures (SRS) an impairment of the endogenous anti-inflammatory pathway glucocorticoid receptor (GR)-annexin A1 (ANXA1) occurs. By administrating exogenous ANXA1, we studied whether pharmacological potentiation of the anti-inflammatory response modifies seizure activity and pathophysiology. We used an in vivo model of temporal lobe epilepsy based on intrahippocampal kainic acid (KA) injection. Video-electroencephalography, molecular biology analyses on brain and peripheral blood samples, and pharmacological investigations were performed in this model. Human epileptic cortices presenting type II focal cortical dysplasia (IIa and b), hippocampi with or without hippocampal sclerosis (HS), and available controls were used to study ANXA1 expression. A decrease of phosphorylated (phospho-) GR and phospho-GR/tot-GR protein expression occurred in the hippocampus during epileptogenesis. Downstream to GR, the anti-inflammatory protein ANXA1 remained at baseline levels while inflammation installed and endured. In peripheral blood, ANXA1 and corticosterone levels showed no significant modifications during disease progression except for an early and transient increase poststatus epilepticus. These results indicate inadequate ANXA1 engagement over time and in these experimental conditions. By analyzing human brain specimens, we found that where significant inflammation exists, the pattern of ANXA1 immunoreactivity was abnormal because the typical perivascular ANXA1 immunoreactivity was reduced. We next asked whether potentiation of the endogenous anti-inflammatory mechanism by ANXA1 administration modifies the disease pathophysiology. Although with varying efficacy, administration of exogenous ANXA1 somewhat reduced the time spent in seizure activity as compared to saline. These results indicate that the anti-inflammatory GR-ANXA1 pathway is defective during experimental seizure progression. The prospect of pharmacologically restoring or potentiating this endogenous anti-inflammatory mechanism as an add-on therapeutic strategy for specific forms of epilepsy is proposed.-Zub, E., Canet, G., Garbelli, R., Blaquiere, M., Rossini, L., Pastori, C., Sheikh, M., Reutelingsperger, C., Klement, W., de Bock, F., Audinat, E., Givalois, L., Solito, E., Marchi, N. The GR-ANXA1 pathway is a pathological player and a candidate target in epilepsy.
- Published
- 2019
- Full Text
- View/download PDF
33. Is AD a Stress-Related Disorder? Focus on the HPA Axis and Its Promising Therapeutic Targets.
- Author
-
Canet G, Hernandez C, Zussy C, Chevallier N, Desrumaux C, and Givalois L
- Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has important health and economic impacts in the elderly. Despite a better understanding of the molecular mechanisms leading to the appearance of major pathological hallmarks ( senile plaques and neurofibrillary tangles ), effective treatments are still lacking. Sporadic AD forms ( 98% of all cases ) are multifactorial, and a panoply of risk factors have been identified. While the major risk factor is aging, growing evidence suggests that chronic stress or stress-related disorders increase the probability to develop AD. An early dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis or stress axis) has been observed in patients. The direct consequence of such perturbation is an oversecretion of glucocorticoids (GC) associated with an impairment of its receptors (glucocorticoid receptors, GR). These steroids hormones easily penetrate the brain and act in synergy with excitatory amino acids. An overexposure could be highly toxic in limbic structures ( prefrontal cortex and hippocampus ) and contribute in the cognitive decline occurring in AD. GC and GR dysregulations seem to be involved in lots of functions disturbed in AD and a vicious cycle appears, where AD induces HPA axis dysregulation, which in turn potentiates the pathology. This review article presents some preclinical and clinical studies focusing on the HPA axis hormones and their receptors to fight AD. Due to its primordial role in the maintenance of homeostasis, the HPA axis appears as a key-actor in the etiology of AD and a prime target to tackle AD by offering multiple angles of action., (Copyright © 2019 Canet, Hernandez, Zussy, Chevallier, Desrumaux and Givalois.)
- Published
- 2019
- Full Text
- View/download PDF
34. Central Role of Glucocorticoid Receptors in Alzheimer's Disease and Depression.
- Author
-
Canet G, Chevallier N, Zussy C, Desrumaux C, and Givalois L
- Abstract
Alzheimer's disease (AD) is the principal neurodegenerative pathology in the world displaying negative impacts on both the health and social ability of patients and inducing considerable economic costs. In the case of sporadic forms of AD (more than 95% of patients), even if mechanisms are unknown, some risk factors were identified. The principal risk is aging, but there is growing evidence that lifetime events like chronic stress or stress-related disorders may increase the probability to develop AD. This mini-review reinforces the rationale to consider major depressive disorder (MDD) as an important risk factor to develop AD and points the central role played by the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids (GC) and their receptors (GR) in the etiology of MDD and AD. Several strategies directly targeting GR were tested to neutralize the HPA axis dysregulation and GC overproduction. Given the ubiquitous expression of GR, antagonists have many undesired side effects, limiting their therapeutic potential. However, a new class of molecules was developed, highly selective and acting as modulators. They present the advantage to selectively abrogate pathogenic GR-dependent processes, while retaining beneficial aspects of GR signaling. In fact, these "selective GR modulators" induce a receptor conformation that allows activation of only a subset of downstream signaling pathways, explaining their capacity to combine agonistic and antagonistic properties. Thus, targeting GR with selective modulators, alone or in association with current strategies, becomes particularly attractive and relevant to develop novel preventive and/or therapeutic strategies to tackle disorders associated with a dysregulation of the HPA axis.
- Published
- 2018
- Full Text
- View/download PDF
35. HIV Neuroinfection and Alzheimer's Disease: Similarities and Potential Links?
- Author
-
Canet G, Dias C, Gabelle A, Simonin Y, Gosselet F, Marchi N, Makinson A, Tuaillon E, Van de Perre P, Givalois L, and Salinas S
- Abstract
Environmental factors such as chemicals, stress and pathogens are now widely believed to play important roles in the onset of some brain diseases, as they are associated with neuronal impairment and acute or chronic inflammation. Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neurodegeneration that ultimately lead to dementia. Neuroinflammation also plays a prominent role in AD and possible links to viruses have been proposed. In particular, the human immunodeficiency virus (HIV) can pass the blood-brain barrier and cause neuronal dysfunction leading to cognitive dysfunctions called HIV-associated neurocognitive disorders (HAND). Similarities between HAND and HIV exist as numerous factors involved in AD such as members of the amyloid and Tau pathways, as well as stress-related pathways or blood brain barrier (BBB) regulators, seem to be modulated by HIV brain infection, leading to the accumulation of amyloid plaques or neurofibrillary tangles (NFT) in some patients. Here, we summarize findings regarding how HIV and some of its proteins such as Tat and gp120 modulate signaling and cellular pathways also impaired in AD, suggesting similarities and convergences of these two pathologies.
- Published
- 2018
- Full Text
- View/download PDF
36. Deletion of plasma Phospholipid Transfer Protein (PLTP) increases microglial phagocytosis and reduces cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's disease.
- Author
-
Mansuy M, Baille S, Canet G, Borie A, Cohen-Solal C, Vignes M, Perrier V, Chevallier N, Le Guern N, Deckert V, Lagrost L, Givalois L, and Desrumaux C
- Abstract
Plasma phospholipid transfer protein (PLTP) binds and transfers a number of amphipathic compounds, including phospholipids, cholesterol, diacylglycerides, tocopherols and lipopolysaccharides. PLTP functions are relevant for many pathophysiological alterations involved in neurodegenerative disorders (especially lipid metabolism, redox status, and immune reactions), and a significant increase in brain PLTP levels was observed in patients with Alzheimer's disease (AD) compared to controls. To date, it has not been reported whether PLTP can modulate the formation of amyloid plaques, i.e. one of the major histopathological hallmarks of AD. We thus assessed the role of PLTP in the AD context by breeding PLTP-deficient mice with an established model of AD, the J20 mice. A phenotypic characterization of the amyloid pathology was conducted in J20 mice expressing or not PLTP. We showed that PLTP deletion is associated with a significant reduction of cerebral Aβ deposits and astrogliosis, which can be explained at least in part by a rise of Aβ clearance through an increase in the microglial phagocytic activity and the expression of the Aβ-degrading enzyme neprilysin. PLTP arises as a negative determinant of plaque clearance and over the lifespan, elevated PLTP activity could lead to a higher Aβ load in the brain., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.
- Published
- 2018
- Full Text
- View/download PDF
37. Management of degenerative lumbar spinal stenosis: an evidence-based review.
- Author
-
Covaro A, Vilà-Canet G, de Frutos AG, Ubierna MT, Ciccolo F, and Caceres E
- Abstract
Lumbar spinal stenosis has become one of the most disabling pathologies in the elderly population.Some additional conditions such as foraminal stenosis or degenerative spondylosis with a history of back pain and leg pain must be considered before treatment.A completely appropriate protocol and unified management of spinal stenosis have not yet been well defined.The objective of this literature review is to provide evidence-based recommendations reflected in the highest-quality clinical literature available to address key clinical questions surrounding the management of degenerative lumbar spinal stenosis. Cite this article: Covaro A, Vilà-Canet G, García de Frutos A, Ubierna MT, Ciccolo F, Caceres E. Management of degenerative lumbar spinal stenosis: an evidence-based review article. EFORT Open Rev 2016;1:267-274. DOI: 10.1302/2058-5241.1.000030., Competing Interests: Conflict of Interest: None declared.
- Published
- 2017
- Full Text
- View/download PDF
38. Thoracolumbar fractures without neurological impairment: A review of diagnosis and treatment.
- Author
-
Vilà-Canet G, García de Frutos A, Covaro A, Ubierna MT, and Caceres E
- Abstract
An appropriate protocol and unified management of thoracolumbar fractures without neurological impairment has not been well defined.This review attempts to elucidate some controversies regarding diagnostic tools, the ability to define the most appropriate treatment of classification systems and the evidence for conservative and surgical methods based on the recent literature. Cite this article: Vilà-Canet G, García de Frutos A, Covaro A, Ubierna MT, Caceres E. Thoracolumbar fractures without neurological impairment: a review of diagnosis and treatment. EFORT Open Rev 2016;1:332-338. DOI: 10.1302/2058-5241.1.000029., Competing Interests: Conflict of interest: Ana Garcia de Frutos declares separate financial relationships with Stryker, DePuy Synths and Biomet. These relationships have no connection to this paper.
- Published
- 2017
- Full Text
- View/download PDF
39. New selective glucocorticoid receptor modulators reverse amyloid-β peptide-induced hippocampus toxicity.
- Author
-
Pineau F, Canet G, Desrumaux C, Hunt H, Chevallier N, Ollivier M, Belanoff JK, and Givalois L
- Subjects
- Alzheimer Disease chemically induced, Alzheimer Disease metabolism, Alzheimer Disease pathology, Animals, Aza Compounds pharmacology, Cognitive Dysfunction drug therapy, Disease Models, Animal, Dose-Response Relationship, Drug, Glucocorticoids blood, Heterocyclic Compounds, 4 or More Rings pharmacology, Hypothalamo-Hypophyseal System, Isoquinolines pharmacology, Male, Mifepristone pharmacology, Mifepristone therapeutic use, Pituitary-Adrenal System, Pyrazoles pharmacology, Rats, Sprague-Dawley, Alzheimer Disease drug therapy, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides toxicity, Aza Compounds therapeutic use, Heterocyclic Compounds, 4 or More Rings therapeutic use, Hippocampus metabolism, Hippocampus pathology, Isoquinolines therapeutic use, Molecular Targeted Therapy, Pyrazoles therapeutic use, Receptors, Glucocorticoid agonists, Receptors, Glucocorticoid antagonists & inhibitors
- Abstract
In Alzheimer's disease (AD), cognitive deficits and psychological symptoms are associated with an early deregulation of the hypothalamic-pituitary-adrenal axis. Here, in an acute model of AD, we investigated if antiglucocorticoid strategies with selective glucocorticoid receptor (GR) modulators (CORT108297 and CORT113176) that combine antagonistic and agonistic GR properties could offer an interesting therapeutic approach in the future. We confirm the expected properties of the nonselective GR antagonist (mifepristone) because in addition to restoring basal circulating glucocorticoids levels, mifepristone totally reverses synaptic deficits and hippocampal apoptosis processes. However, mifepristone only partially reverses cognitive deficit, effects of the hippocampal amyloidogenic pathway, and neuroinflammatory processes, suggesting limits in its efficacy. By contrast, selective GR modulators CORT108297 and CORT113176 at a dose of 20 and 10 mg/kg, respectively, reverse hippocampal amyloid-β peptide generation, neuroinflammation, and apoptotic processes, restore the hippocampal levels of synaptic markers, re-establish basal plasma levels of glucocorticoids, and improve cognitive function. In conclusion, selective GR modulators are particularly attractive and may pave the way to new strategies for AD treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
40. Cell-free cartilage engineering approach using hyaluronic acid-polycaprolactone scaffolds: a study in vivo.
- Author
-
Lebourg M, Martínez-Díaz S, García-Giralt N, Torres-Claramunt R, Gómez-Tejedor JA, Ribelles JL, Vila-Canet G, and Monllau JC
- Subjects
- Animals, Cell-Free System, Microscopy, Electron, Scanning, Rabbits, Thermogravimetry, Hyaluronic Acid chemistry, Polyesters chemistry, Tissue Engineering, Tissue Scaffolds
- Abstract
Polycaprolactone scaffolds modified with cross-linked hyaluronic acid were prepared in order to establish whether a more hydrophilic and biomimetic microenvironment benefits the progenitor cells arriving from bone marrow in a cell-free tissue-engineering approach. The polycaprolactone and polycaprolactone/hyaluronic acid scaffolds were characterized in terms of morphology and water absorption capacity. The polycaprolactone and polycaprolactone/hyaluronic acid samples were implanted in a chondral defect in rabbits; bleeding of the subchondral bone was provoked to generate a spontaneous healing response. Repair at 1, 4, 12, and 24 weeks was assessed macroscopically using the International Cartilage Repair Society score and the Oswestry Arthroscopy Score and microscopically using immunohistological staining for collagen type I and type II, and for Ki-67. The presence of hyaluronic acid improves scaffold performance, which supports a good repair response without biomaterial pre-seeding.
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.