Tag Archives: animal-model

13th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals

2022-04-07NMR Events & Coursesanimal-model, in-vivo, MRI, MRS, workshopSilvia

Workshop dates:	May 24th – 27th, 2022
Registration deadline:	May 13th, 2022
Registration:	download the registration form and email it to
Capacity:	Workshop limited to 4 participants (first come, first served)
Contact person:	Silvia Lope-Piedrafita, PhD ()

This course combines a comprehensive series of lectures on the technology of Magnetic resonance spectroscopy and imaging (MRS/MRI) with hands-on laboratory sessions to provide practical demonstrations of key concepts and procedures for preclinical studies.

Whether you are considering MRI as a research tool in your lab or just would like to learn more about MRI, this workshop addresses practical aspects of experimental MRI with laboratory animals and provide valuable hands-on experience on a 7 Tesla Bruker BioSpec spectrometer.

See the workshop brochure for more information, or contact via email.

12th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals

2021-01-29News from the SeRMN, NMR Events & Courses, Uncategorizedanimal-model, biomedical research, MRI, MRS, MRSI, workshopSilvia

Workshop dates:	February 15th – 18th, 2021
Registration deadline:	February 8th, 2021
Registration:	online
Capacity:	Workshop limited to 4 participants (first come, first served)
Contact person:	Silvia Lope-Piedrafita, PhD ()

See the workshop brochure for more information or contact Dr. Silvia Lope via email.

In vivo MRI/MRS longitudinal study of immunotherapy in Alzheimer’s

2020-04-30Methods & Applications, News from the SeRMN, Our PublicationsAlzheimer, animal-model, biomedical research, in-vivo, metabolic profiling, Methods&Applications, Mouse Atlas, MRI, MRS, therapySilvia

Progression of Alzheimer’s disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy by Güell-Bosch J, Lope-Piedrafita S, Esquerda-Canals G, Montoliu-Gaya L, and Villegas S. NMR in Biomedicine 33(5):e4263; DOI: 10.1002/nbm.4263.

Alzheimer’s disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. In recent years, Aβ-immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv-h3D6 generated by our research group derives from this monoclonal antibody, which targets the N-terminal of the Aβ peptide and recognizes monomers, oligomers and fibrils.

In this study, 3xTg-AD mice were intraperitoneally and monthly treated with 100 μg of scFv-h3D6 (a dose of ~3.3 mg/kg) or PBS, from 5 to 12 months of age (-mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques allow, in a non-invasive manner, to draw an in vivo picture of concrete aspects of the pathology and to monitor its development across time. Compared with the genetic background, 3xTg-AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aβ1-42 at 12-mo, and an inflammation process at this age, in both the hippocampus (IL-6 and mIns) and cortex (IL-6). In addition, treatment with scFv-h3D6 partially recovered the values in brain volume, and Aβ, IL-6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.

Prenatal cerebral and cardiac metabolic changes in a rabbit model of fetal growth restriction

2019-01-03Our Publications, Our Research13C-NMR, animal-model, hrmMiquel

Simões, Rui V., Miquel E. Cabañas, Carla Loreiro, Miriam Illa, Fatima Crispi & Eduard Gratacós. 2018. Assessment of prenatal cerebral and cardiac metabolic changes in a rabbit model of fetal growth restriction based on ¹³C-labelled substrate infusions and ex vivo multinuclear HRMAS. PLOS ONE 13(12). e0208784. DOI: 10.1371/journal.pone.0208784

Background: We have used a previously reported rabbit model of fetal growth restriction (FGR), reproducing perinatal neurodevelopmental and cardiovascular impairments, to investigate the main relative changes in cerebral and cardiac metabolism of term FGR fetuses during nutrient infusion.

Methods: FGR was induced in 9 pregnant New Zealand rabbits at 25 days of gestation: one horn used as FGR, by partial ligation of uteroplacental vessels, and the contralateral as control (appropriate for gestation age, AGA). At 30 days of gestation, fasted mothers under anesthesia were infused i.v. with 1-¹³C-glucose (4 mothers), 2-¹³C-acetate (3 mothers), or not infused (2 mothers). Fetal brain and heart samples were quickly harvested and frozen down. Brain cortex and heart apex regions from 30 fetuses were studied ex vivo by HRMAS at 4°C, acquiring multinuclear 1D and 2D spectra. The data were processed, quantified by peak deconvolution or integration, and normalized to sample weight.

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Beneficial effects of Uric Acid Treatment After Stroke in Hypertensive Rats

2018-12-19Methods & Applications, NMR Bibliographyanimal-model, MRI, strokeSilvia

Jiménez-Xarrié, Elena, Belén Pérez, Ana Paula Dantas, Lídia Puertas-Umbert, Joan Martí-Fabregas, Ángel Chamorro, Anna Maria Planas, Elisabet Vila, Francesc Jiménez-Altayó. 2018. Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery Remodelling and Attenuates Brain Damage in Spontaneously Hypertensive Rats. Translational Stroke Research. DOI: 10.1007/s12975-018-0661-8

Hypertension is the most important modifiable risk factor for stroke and is associated with poorer post-stroke outcomes. The antioxidant uric acid is protective in experimental normotensive ischaemic stroke. However, it is unknown whether this treatment exerts long-term protection in hypertension. The authors aimed to evaluate the impact of transient intraluminal middle cerebral artery (MCA) occlusion (90min)/reperfusion (1–15 days) on brain and vascular damage progression in adult and spontaneously hypertensive rats (SHR) treated with uric acid. Ischaemic brain damage was assessed longitudinally with magnetic resonance imaging at the Nuclear Magnetic Resonance Service of the Universitat Autònoma de Barcelona.

In SHR rats, more severe brain damage and poorer neurofunctional outcomes were coupled to higher cortical cerebral blood flow at the onset of reperfusion, a transient increase in oxidative stress and long-lasting stroke-induced MCA hypertrophic remodelling. Thus, stroke promotes larger brain and vascular damage in hypertensive rats that persists for long-time. Uric acid administered during early reperfusion attenuated short- and long-term brain injuries in both normotensive and hypertensive rats, an effect that was associated with abolishment of the acute oxidative stress response and prevention of stroke-induced long lasting MCA remodelling in hypertension. These results suggest that uric acid might be an effective strategy to improve stroke outcomes in hypertensive subjects.

MRI/MRS in treated Alzheimer mice

2018-10-10Methods & Applications, News from the SeRMN, Our PublicationsAlzheimer, animal-model, biospec, metabolomics, MRI, MRSSilvia

Montoliu-Gaya, Laia, Jofre Güell-Bosch, Gisela Esquerda-Canals, Alejandro R. Roda, Gabriel Serra-Mir, Silvia Lope-Piedrafita, José Luís Sánchez-Quesada & Sandra Villegas. 2018. Differential effects of apoE and apoJ mimetic peptides on the action of an anti-Aβ scFv in 3xTg-AD mice. Biochemical Pharmacology 155. 380–392. DOI: 10.1016/j.bcp.2018.07.012

Anti-Aβ immunotherapy has emerged as a promising approach to treat Alzheimer’s disease (AD). The single-chain variable fragment scFv-h3D6 is an anti-Aβ antibody fragment that lacks the Fc region, which is associated with the induction of microglial reactivity by the full-length monoclonal antibody bapineuzumab. ScFv-h3D6 was previously shown to restore the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ) in a tripletransgenic- AD (3xTg-AD) mouse model. Since apoE and apoJ play an important role in the development of AD, we aimed to study the in vivo effect of the combined therapy of scFv-h3D6 with apoE and apoJ mimetic peptides (MPs).

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11th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals

2018-04-20News from the SeRMN, NMR Events & Coursesanimal-model, biospec, MRI, MRS, MRSI, workshopSilvia

Workshop dates:	June 25th – 28th, 2018
Registration deadline:	June 10th, 2018
Registration:	online
Capacity:	Workshop limited to 4 participants (first come, first served)
Contact person:	Silvia Lope-Piedrafita, PhD ()

See the workshop brochure for more information or contact Dr. Silvia Lope via email.

NEW BOOK RELEASE: “Preclinical MRI methods and protocols”

2018-04-05Methods & Applications, News from the SeRMN, NMR Bibliography, Our Publicationsanimal-model, biospec, Methods&Applications, MRI, MRI Books, MRS, MRSI, NMR BooksSilvia

García Martín, María Luisa & Pilar López Larrubia (eds.). 2018. Preclinical MRI. Methods in Molecular Biology series. Springer New York. DOI: 10.1007/978-1-4939-7531-0

This book was conceived with the idea of providing an update on a wide variety of preclinical MRI methods and protocols to help technicians and researchers interested in this technology. The basics of MRI physics are introduced, followed by chapters describing updated methodology and protocols for some standard and more advanced MRI techniques covering diffusion, perfusion, functional imaging, in-vivo spectroscopy (proton and heteronuclear), susceptibility contrast MRI… The book also contains some chapters where some applications of those methods are illustrated in animal models of several diseases including cancer, stroke and neurodegeneration. Protocols are described in a step-by-step approach, with interesting notes and tips at the end of each chapter, which -a priori- should allow the new worker to obtain successful results with the first attempt ;o) .

Assessment of biodistribution using mesenchymal stromal cells

2017-12-20Our Publicationsanimal-model, biospec, cell labelling, cell tracking, MRI, SPIOSilvia

“Assessment of biodistribution using mesenchymal stromal cells: Algorithm for study design and challenges in detection methodologies” by Reyes B, Coca MI, Codinach M, López-Lucas MD, Del Mazo-Barbara A, Caminal M, Oliver-Vila I, Cabañas V, S. Lope-Piedrafita, García-López J, Moraleda JM, Fontecha CG, Vives J. Cytotherapy. 2017 :1060-1069. doi: 10.1016/j.jcyt.2017.06.004.

Biodistribution of candidate cell-based therapeutics is a critical safety concern that must be addressed in the preclinical development program. We aimed to design a decision tree based on a series of studies included in actual dossiers approved by competent regulatory authorities, noting that the design, execution and interpretation of pharmacokinetics studies using this type of therapy is not straightforward and presents a challenge for both developers and regulators. This work contributes to the standardization in the design of biodistribution studies by improving methods for accurate assessment of safety.

Eight studies were evaluated for the definition of a decision tree, in which mesenchymal stromal cells (MSCs) were administered to mouse, rat and sheep models using diverse routes (local or systemic), cell labeling (chemical or genetic) and detection methodologies (polymerase chain reaction (PCR), immunohistochemistry (IHC), fluorescence bioimaging, and magnetic resonance imaging (MRI). Moreover, labeling and detection methodologies were compared in terms of cost, throughput, speed, sensitivity and specificity.

Metronomic treatment in immunocompetent preclinical glioblastoma

2017-07-07Our Publications, Our Researchanimal-model, biospec, cancer, metabolomics, MRI, MRS, MRSI, therapySilvia

“Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide” by by L. Ferrer-Font, N. Arias-Ramos, S. Lope-Piedrafita, M. Julià-Sapé , M. Pumarola, C. Arús and A. P. Candiota. NMR Biomed. 2017. DOI: 10.1002/nbm.3748.

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. In preceding years, efforts have focused in new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, as for example the “metronomic” approaches.

We have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/Kg) or TMZ (range 140-240 mg/Kg) metronomic administration (every 6 days) were performed in tumor-bearing mice. Tumor evolution was monitored at 7T with T2-weighted MRI, Diffusion weighted imaging and MRSI-based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6+21.0 days, n=30) compared to control (19.4+2.4 days, n=18). Also, it was found a clear edema appearance during chemotherapeutic treatment suggesting inflammatory associated processes. The necropsy performed in mice cured from GBM after high TMZ cumulative dosage (980-1400 mg/Kg) revealed lymphoma incidence.

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