54 research outputs found
Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior
RATIONALE: Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment.
OBJECTIVE: Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity.
METHODS: Juvenile Sprague-Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8).
RESULTS: Memantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections.
CONCLUSIONS: The lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI
Effects of Aliskiren on Stroke in Rats Expressing Human Renin and Angiotensinogen Genes
OBJECTIVE: Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects. METHODS: Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kg*d) or candesartan (1.5 or 10 mg/kg*d) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions. RESULTS: The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core. CONCLUSIONS: Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further
Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer
Introduction Cardiovascular disease (CVD) is an
important cause of death in breast cancer survivors.
Some breast cancer treatments including anthracyclines,
trastuzumab and radiotherapy can increase the risk of
CVD, especially for patients with pre-existing CVD risk
factors. Early identification of patients at increased CVD
risk may allow switching to less cardiotoxic treatments,
active surveillance or treatment of CVD risk factors. One of
the strongest independent CVD risk factors is the presence
and extent of coronary artery calcifications (CAC). In
clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer
treated with radiotherapy routinely undergo radiotherapy
planning CT scans of the chest, and those scans could
provide the opportunity to routinely assess CAC before a
potentially cardiotoxic treatment. The Bragatston study
aims to investigate the association between calcifications
in the coronary arteries, aorta and heart valves (hereinafter
called ‘cardiovascular calcifications’) measured
automatically on planning CT scans of patients with breast
cancer and CVD risk.
Methods and analysis In a first step, we will optimise
and validate a deep learning algorithm for automated
quantification of cardiovascular calcifications on
planning CT scans of patients with breast cancer.
Then, in a multicentre cohort study (University Medical
Center Utrecht, Utrecht, Erasmus MC Cancer Institute,
Rotterdam and Radboudumc, Nijmegen, The Netherlands),
the association between cardiovascular calcifications
measured on planning CT scans of patients with breast
cancer (n≈16 000) and incident (non-)fatal CVD events
will be evaluated. To assess the added predictive value of
these calcifications over traditional CVD risk factors and
treatment characteristics, a case-cohort analysis will be
performed among all cohort members diagnosed with a
CVD event during follow-up (n≈200) and a random sample
of the baseline cohort (n≈600).
Ethics and dissemination The Institutional Review
Boards of the participating hospitals decided that the
Medical R
An Open Resource for Non-human Primate Imaging.
Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets
Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats
Non-invasive measurement of brain damage in a primate model of multiple sclerosis
Early recognition of whether a product has potential as a new therapy for treating multiple sclerosis (MS) relies upon the quality of the animal models used in the preclinical trials. The promising effects of new treatments in rodent models of experimental autoimmune encephalomyelitis (EAE) have rarely been reproduced in patients suffering from MS. EAE in outbred marmoset monkeys, Callithrix jacchus, is a valid new model, and might provide an experimental link between EAE in rodent models and human MS. Using magnetic resonance imaging techniques similar to those used in patients suffering from MS pathological abnormalities in the brain, white matter of the animal can be visualized and quantified. Moreover, NMR spectroscopy, in combination with pattern recognition, offers an advanced uroscopic technique for the identification of biomarkers of inflammatory demyelination
Fast progression of recombinant human myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis, in marmosets is associated with the activation of MOG(34-56)-specific cytotoxic T cells
Non-human primate models of multiple sclerosis
The phylogenetic proximity between non-human primate species and humans is reflected by a high degree of immunological similarity. Non-human primates therefore provide important experimental models for disorders in the human population that are caused by the immune system, such as autoimmune diseases. In this paper we describe non-human primate models of multiple sclerosis, a chronic inflammatory and demyelinating disease of the human central nervous system. While reviewing data from the literature and our own research we will discuss the unique role of such models in the research of basic disease mechanisms and the development of new therapies
Non-human primate models of multiple sclerosis
The phylogenetic proximity between non-human primate species and humans is reflected by a high degree of immunological similarity. Non-human primates therefore provide important experimental models for disorders in the human population that are caused by the immune system, such as autoimmune diseases. In this paper we describe non-human primate models of multiple sclerosis, a chronic inflammatory and demyelinating disease of the human central nervous system. While reviewing data from the literature and our own research we will discuss the unique role of such models in the research of basic disease mechanisms and the development of new therapies
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