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中国神经科学学会第十二届全国学术会议

作者： rodrigo a.cunha CNC-Center for Neuroscience and Cell Biology University of Coimbra Faculty of Medicine University of Coimbra

Regular consumption of caffeine prevents age-related memory dysfunction and inversely correlates with the incidence of Alzheimer’s disease(AD) and animal models confirmed this prophylactic benefit of caffeine(J Alzheimers Dis 20:S95). In keeping with caffeine acting as an antagonist of adenosine receptors, caffeine neuroprotection is mimicked by blockade or inactivation of adenosine A2 A receptors(AR)(J Neurochem 139:1019). In APP/PS1 or in 3 x Tg mouse models of AD, the genetic or pharmacological blockade of AR reverts memory deficits at their onset. Surprisingly, there were no alteration of the density or function of AMPA or NMDA receptors, and AR blockade was sufficient to recover the hampered synaptic plasticity in hippocampal excitatory synapses of AD mice. Furthermore, pharmacological or optogenetic over-activation of AR in naive mice was sufficient to trigger memory deficits. We next enquired if this involved neuronal or astrocytic AR. We report that b-amyloid peptides(Aβ)-induced depression of hippocampal long-term potentiation was abrogated in neuronal(CAM-KII-driven)-AR knockout mice and was unchanged in astrocytic(GFAP-driven)-AR knockout mice, thus implicating neuronal AR. We next tested if AR over-activation resulted from increased AR density and/or from increased formation of adenosine activating AR, which is known to be ATP-derived adenosine formed by CD73, an ecto-5’-nucleotidase(J Neurosci 33:11390). As occurs in AD patients(Brain Pathol 18:211), we report an up-regulation of AR in hippocampal synapses, namely in glutamatergic synapses, of different early AD mouse models. We also found an increased ATP release and an increased density and activity of CD73 in hippocampal synaptosomes of icv Aβ-treated mice with memory deficits, and the blockade of CD73 phenocopied AR blockade in the control of synaptic plasticity and memory deficits of these early AD-like mice. This shows that aberrant AR over-function is paramount to disrupt synaptic plasticity and

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Adenosine A2A receptors induce the formation of abnormal secondary axons in rat hippocampal neurons: a new target to arrest epileptogenesis

Adenosine A2A receptors induce the formation of abnormal sec...

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中国神经科学学会第十二届全国学术会议

作者： Xinli Xu Sofia Al?ada-Morais Nélio M.Gon?alves Joana M.Marques Sergio Valbuena Rui O.Beleza Francisco Q.Gon?alves Sofia Ferreira Juan Lerma rodrigo a.cunha Ricardo J.Rodrigues CNC-Center for Neuroscience and Cell Biology University of Coimbra

Current anti-epileptic drugs mostly control convulsions with a limited efficacy, and do not seize epileptogenesis. One of the structural-functional modifications occurring during epileptogenesis is an abnormal axonal sprouting. The hippocampal mossy fiber(MF) sprouting found in patients and in animal models of temporal lobe epilepsy(TLE)(Neuroscience14, 375-403) generates an aberrant excitatory feedback circuit in granule cells that is thought to contribute to the hyperexcitability underlying the seizure-prone state(Neurochem. Res.28, 1649-58). However, the mechanism underlying this aberrant re-wiring is still poorly understood. There is now a growing evidence for a sustained increase in extracellular ATP levels in different pathological conditions, prompting ATP as a danger signal in the brain(Front. Neurosci.9:148). Accordingly, we now measured a sustained increase of the evoked release of ATP from hippocampal nerve terminals of Sprague-Dawley rats subjected to Status Epilepticus(SE) induced by pilocarpineinjection. Concomitantly, we found in developing rat hippocampal neurons that the pharmacological activation of adenosine A receptors(ARs) with the selective agonist CGS21680(30 n M) induces the formation of abnormal secondary axons. This prompted us to propose that this abnormal sprouting is due to an abnormal reactivation of the developmental-related AR-driven axon formation and outgrowth. We have now found in hippocampal organotypic slices that the spontaneous MF sprouting was attenuated by the pharmacological blockade of ARs, since the current densities(p A/p F) recorded were significantly lower in the slices cultured in the presence of the selective AR antagonist SCH58261(100 n M). More importantly, we found that the animals subjected to a long-term systemic treatment with SCH58261(0.1 mg/kg, i.p.), beginning 10 hours after pilocarpine-induced SE in rats, displayed significantly less hippocampal MF sprouting. Interestingly, CD73 knockout(CD73 KO) mice(lackin

关键词： A2A receptors Mossy fiber sprouting Status epilepticus CD73

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Comparison of Surgical Techniques Used in Treating Acromioclavicular Dislocation in Patients Participating in Sports: A Systematic Review

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Open Journal of Orthopedics 2024年第1期14卷 41-52页

作者： Walter Hugo Brandão Nascimento Paulo Renan Matos Sucupira.cunha João Pedro Pimentel Abreu Lethycia Pereira Rosa Kamilly Iêda Silva Veigas rodrigo Martins Silva Caetano Orthopedic and Trauma Surgeon Brazilian Army Rio de Janeiro Brazil Orthopedic and Trauma Surgeon S&atildeo Luís Brazil Scholarship Holder National Council for Scientific and Technological Development (CNPq) S&atildeo Luís Brazil School of Medicine Federal University of Maranh&atildeo (UFMA) S&atildeo Luís Brazil Orthopedic and Trauma Surgeon Shoulder and Elbow Surgery Specialist University Hospital of the Federal University of Maranh&atildeo (HUUFMA/EBSERH) S&atildeo Luís Brazil

Introduction: The acromioclavicular joint is a superficial diarthrodial joint that surrounds the medial articular facet of the acromion and the distal portion of the clavicle. Due to its anatomy and biomechanics, it is highly susceptible to trauma and in young men who play contact sports, acromioclavicular dislocation is common. This article aimed to systematically review the literature and compare the surgical techniques used in the treatment of acromioclavicular dislocation in patients who practice sports. Methods: This systematic review was conducted according to the International Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Eligible studies for this systematic review included articles in English or Spanish published between 2013 and 2023, which mention the occurrence of acromioclavicular dislocation during sports practices. Additionally, only studies that addressed the surgical treatment of acromion-clavicular dislocation and contained original data on the topic were included. Results: We found 144 eligible studies after searching the LILACS and PubMed databases. Based on the inclusion and exclusion criteria and the reviewers’ consensus, we selected four studies for the systematic review. 133 patients with AC joint displacement were evaluated. Mean Age: approximately 31.90 years. 81.92 of these injuries occurred during sports practice. Surgical Procedures Used: titanium plates fixation (49 patients), arthroscopy (24), single tunnel technique (30) and coracoid sling technique (30). The results of the visual analog scale and Constant-Murley scores varied between the techniques used. Twenty-two complications after surgical treatment were identified. Conclusion: A significant variability of operative techniques can be used in the surgical approach of acromioclavicular dislocation, such as arthroscopy, single tunnel, coracoid sling and titanium plates. Although it presented excellent functional results compared to the other three tech

关键词： Acromioclavicular Joint Shoulder Dislocation Surgical Procedure Postoperative Complications Postoperative Care

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Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

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Journal of Sport and Health Science 2024年第4期13卷 548-558,F0003页

作者： Hugo de Luca Correa Lysleine Alves Deus Dahan da.cunha Nascimento Nicholas Rolnick rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araujo Carmen Tzanno-Martins Fernanda Silveira Tavares Luiz Sinesio Silva Neto Claudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitoria Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate Program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil Graduate Program of Genomic Sciences and Biotechnology Brasılia 71966-700Brazil

Background:Hemodialysis(HD) per se is a risk factor for *** the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training *** aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this ***:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of 70 years old),and HD ***,RE+BFR significantly increases D-dimer after 4 *** with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

关键词： Blood-flow restriction Chronic kidney disease Coagulation Hemodialysis Vascular occlusion exercises

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G protein-coupled receptor 37(GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

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Neural Regeneration Research 2019年第11期14卷 1912-1914页

作者： Xavier Morato rodrigo A. cunha Francisco Ciruela Unitat de Farmacologia Departament Patologia i Terapeutica ExperimentalFacultat de MedicinaInstituto de Investigacion Biomedica de Bellvitge (IDIBELL)Universitat de BarcelonaL’Hospitalet de LlobregatBarcelonaSpainInstitut de NeurocienciesUniversitat de BarcelonaBarcelonaSpain (Morato X Ciruela F) Center for Neuroscience and Cell Biology (CNC)-Center for Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugalFaculty of MedicineUniversity of CoimbraCoimbraPortugal

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein- coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morato et al., 2017;Sokolina et al., 2017).

关键词： G protein-coupled receptor 37(GPR37) important modulator adenosinergic transmission

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Response to Commentary by Dr. Matthew J. Clarkson on

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Journal of Sport and Health Science 2024年第5期13卷 670-671页

作者： Hugo de Luca Corrêa Lysleine Alves Deus Dahan da.cunha Nascimento Nicholas Rolnick rodrigo Vanerson Passos Neves Andrea Lucena Reis Thais Branquinho de Araújo Carmen Tzanno-Martins Fernanda Silveira Tavares Luiz Sinésio Silva Neto Cláudio Avelino Rodrigues Santos Paolo Lucas Rodrigues-Silva Fernando Honorato Souza Vitória Marra da Motta Vilalva Mestrinho Rafael Lavarini dos Santos Rosangela Vieira Andrade Jonato Prestes Thiago dos Santos Rosa Post-graduate Program of Physical Education Catholic University of BrasıliaBrasılia 71966-700Brazil The Human Performance Mechanic Lehman CollegeNew YorkNY 10011USA Clinical Group Home Dialysis Center and RenalClass Sao Paulo 01239-040Brazil Department of Medicine Catholic University of BrasıliaBrasılia 71966-700Brazil Faculty of Medicine Federal University of TocantinsTocantins 77001-090Brazil Embrapa Genetic Resources and Biotechnology Brasılia 70770-917Brazil g Graduate Program of Genomic Sciences and Biotechnology Brasılia 71966-700Brazil

Dear editor:We sincerely thank Matthew *** for his insightful commentary1 on our recent publication in the Journal of Sport and Health Science.2 Clarkson's pioneering work in the development and application of blood flow restriction (BFR) exercise protocols has undeniably laid the groundwork for subsequent investigations in this field,including our own.(3-6)His commentary not only highlights the relevance and timeliness of our study but also offers valuable perspectives on refining safety considerations for intradialytic BFR exercise among hemodialysis patients.

关键词： patients application flow

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Punch‑excised explants of bovine mammary gland to model early immune response to infection

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2649-2662页

作者： Pablo Gomes Noleto Florence B.Gilbert Christelle Rossignol Patricia.cunha Pierre Germon Pascal Rainard rodrigo Prado Martins ISP INRAEUniversitéde ToursUMR1282NouzillyFrance

Background Mammary gland(MG)infections(mastitis)are frequent diseases of dairy cows that affect milk quality,animal welfare and farming *** infections are commonly associated with the bacteria Escherichia coli and Staphylococcus *** in vitro models have been used to investigate the early response of the MG to bacteria,but the role of the teat in mastitis pathogenesis has received less *** this study,we used punch-excised teat tissue as an ex vivo model to study the immune mechanisms that arise early during infection when bacteria have entered the *** Cytotoxicity and microscopic analyses showed that bovine teat sinus explants have their morphology and viability preserved after 24 h of culture and respond to ex vivo stimulation with TLR-agonists and *** and *** trigger stronger inflammatory response in teat when compared to LTA and ***,leading to a higher produc-tion of IL-6 and IL-8,as well as to an up-regulation of proinflammatory *** also demonstrated that our ex vivo model can be applied to frozen-stored *** In compliance with the 3Rs principle(replacement,reduction and refinement)in animal experimenta-tion,ex vivo explant analyses proved to be a simple and affordable approach to study MG immune response to *** model,which better reproduces organ complexity than epithelial cell cultures or tissue slices,lends itself particularly well to studying the early phases of the MG immune response to infection.

关键词： Bovine teat Escherichia coli Explant Mastitis Staphylococcus aureus 3Rs

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Adenosine A2A Receptor as a novel therapeutic target for Parkinson's disease: what are the challenges?

Adenosine A2A Receptor as a novel therapeutic target for Par...

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中国神经科学学会第十二届全国学术会议

作者： rodrigo cunha University of Coimbra

Parkinson’s disease(PD) is the second most common neurodegenerative disease, affecting % populations at age >60 years old. Based on the concentrated striatal expression of adenosine A2 A receptor(A2 AR), the antagonistic adenosine A2 Adopamine D2 receptor interactions in the striatum, and preclinical studies demonstrating motor benefits in rodent and non-human primate models of Parkinson’s disease(PD), A2 AR antagonists have clinically pursued and emerged as a leading non-dopaminergic treatment for motor deficits in PD over the past decade. First, at least seven double blind, placebo controlled, clinical phase IIb and III trials of A2 AR antagonists) involving a total of >3000 advanced PD patients were reported, confirming its mild but clinically significant motor benefit in advanced PD patients and leading to an approval of istradefylline in Japan for the treatment of PD patients. Second, several large, prospective epidemiological studies, together with animal studies, strongly suggest that A2 AR antagonists also confer a neuroprotective effect in PD. In this talk, I will summarize our previous and ongoing work contributing to the exciting development by providing the first and recently new experimental evidence for neuroprotection by caffeine and A2 AR antagonists, offering the neurobiological basis for the inverse relationship between caffeine consumption and the risk of developing PD. Furthermore, I will describe our recent effort to identify the striatopallidal A2 AR as a promising target for controlling cognitive impairments in PD models. In particular, we have developed a novel optogenetic(i.e opto A2 AR) approach to control striatopallidal A2 AR signalling in behaving animals with unparalleled spatiotemporal resolution. Our recent optogenetic and genetic studies demonstrated a new therapeutic potential for reversing cognitive impairments of PD by A2 AR modulation of working memory and goal-directed behavior.

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使用分叉支架型人工血管行完全腔内治疗胸腹部主动脉瘤的方法

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中国普通外科杂志 2013年第6期22卷 683-684页

作者： Marcelo Ferreira Luiz Lanziotti rodrigo cunha 巴西里约热内卢SITE-血管腔内技术中心

此视频按步骤描述了使用分叉支架型血管完全腔内治疗胸腹部主动脉瘤的方法。我们比较了术前和术后CT上的变化并显示此项技术的3D及真实图像。

关键词：主动脉瘤腔内治疗支架视频

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Constructal design method dealing with stiffened plates and symmetry boundaries

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Theoretical & Applied Mechanics Letters 2020年第5期10卷 366-376页

作者： rodrigo R.Amaral Grégori S.Troina Cristiano Fragassa Ana Pavlovic Marcelo L.cunha Luiz A.O.Rocha Elizaldo D.dos Santos Liércio A.Isoldi School of Engineering Federal University of Rio GrandeRio GrandeBrazil Advanced Applications in Mechanical Engineering and Materials Technology University of BolognaBolognaItaly Departament of Mechanical Engineering University of Vale do Rio dos SinosSão LeopoldoBrazil

A new computational procedure for modelling the structural behavior of stiffened plates with symmetry boundary conditions is here *** uses two-dimensional finite elements as a way to decrease computational time without losing precision thanks to a relatively small number of elements applied for analyzing out-of-plane displacements(deflections)and ***,the constructal design method was included in the procedure,together with the exhaustive search technique,with the scope to optimize the stress/strain status of stiffened plates by design *** the purpose,a reference plate without stiffeners was initially design and used as starting *** of the volume was reshaped into stiffeners:thickness was reduced maintaining unchanged weight,length and *** main goal was to minimize strains and stresses by geometric *** demonstrated that,thanks to this design procedure,it is always possible to find an adequate geometry transformation from reference plate into stiffeners,allowing significant improvements in mechanical behavior.

关键词： Deflection minimization Stress minimization Optimal design Plates with stiffeners Bending

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