Protocol for the systematic review of age and sex in preclinical models of age-correlated diseases.

The translation of animal-based biomedical research into clinical research is often inadequate. Maximizing translation should be central to animal research on human diseases, guiding researchers in study design and animal model selection. However, practical considerations often drive the choice of animal model, which may not always reflect key patient characteristics, such as sex and age, impacting the disease's course.

Lockbox enrichment facilitates manipulative and cognitive activities for mice.

Background: Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing (CH) and super-environmental enrichment (SEE).

Anti-LINGO-1 treatment restores myelination of corticospinal tract neurons and improves functional recovery after stroke.

Demyelination of corticospinal tract neurons contributes to long-term disability after cortical stroke. Nonetheless, poststroke myelin loss has not been addressed as a therapeutic target, so far. We hypothesized that an antibody-mediated inhibition of the Nogo receptor-interacting protein (LINGO-1, leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein) may counteract myelin loss, enhance remyelination and axonal growth, and thus promote functional recovery following stroke.

Challenges and advanced concepts for the assessment of learning and memory function in mice.

The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments.

Development of an IntelliCage-based cognitive bias test for mice.

The cognitive bias test is used to measure the emotional state of animals with regard to future expectations. Thus, the test offers a unique possibility to assess animal welfare with regard to housing and testing conditions of laboratory animals. So far, however, performing such a test is time-consuming and requires the presence of an experimenter.

Automatic classification of experimental models in biomedical literature to support searching for alternative methods to animal experiments.

Current animal protection laws require replacement of animal experiments with alternative methods, whenever such methods are suitable to reach the intended scientific objective. However, searching for alternative methods in the scientific literature is a time-consuming task that requires careful screening of an enormously large number of experimental biomedical publications. The identification of potentially relevant methods, e.

Effects of more natural housing conditions on the muscular and skeletal characteristics of female C57BL/6J mice.

Background: Enrichment of home cages in laboratory experiments offers clear advantages, but has been criticized in some respects. First, there is a lack of definition, which makes methodological uniformity difficult. Second, there is concern that the enrichment of home cages may increase the variance of results in experiments.

Rating enrichment items by female group-housed laboratory mice in multiple binary choice tests using an RFID-based tracking system.

Laboratory mice spend most of their lives in cages, not experiments, so improving housing conditions is a first-choice approach to improving their welfare. Despite the increasing popularity of enrichment, little is known about the benefits from an animal perspective. For a detailed analysis, we categorized enrichment items according to their prospective use into the categories 'structural', 'housing', and 'foraging'.

A guide to open science practices for animal research.

Translational biomedical research relies on animal experiments and provides the underlying proof of practice for clinical trials, which places an increased duty of care on translational researchers to derive the maximum possible output from every experiment performed. The implementation of open science practices has the potential to initiate a change in research culture that could improve the transparency and quality of translational research in general, as well as increasing the audience and scientific reach of published research. However, open science has become a buzzword in the scientific community that can often miss mark when it comes to practical implementation.

Bored at home?-A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice.

Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans, it may very well describe the lives of many laboratory animals housed in small, barren cages. To make the cages less monotonous, environmental enrichment is often proposed.

Determining the value of preferred goods based on consumer demand in a home-cage based test for mice.

From the preference of one good over another, the strength of the preference cannot automatically be inferred. While money is the common denominator to assess the value of goods in humans, it appears difficult at first glance to put a price tag on the decisions of laboratory animals. Here we used consumer demand tests to measure how much work female mice expend to obtain access to different liquids.

Evaluation of different types of enrichment - their usage and effect on home cage behavior in female mice.

Numerous studies ascertained positive effects of enriched environments on the well-being of laboratory animals including behavioral, physiological and neurochemical parameters. Conversely, such conclusions imply impaired animal welfare and health in barren husbandry conditions. Moreover, inappropriate housing of laboratory animals may deteriorate the quality of scientific data.

Roaming in a Land of Milk and Honey: Life Trajectories and Metabolic Rate of Female Inbred Mice Living in a Semi Naturalistic Environment.

Despite tremendous efforts at standardization, the results of scientific studies can vary greatly, especially when considering animal research. It is important to emphasize that consistent different personality-like traits emerge and accumulate over time in laboratory mice despite genetic and environmental standardization. To understand to what extent variability can unfold over time, we conducted a long-term study using inbred mice living in an exceptionally complex environment comprising an area of 4.

Behavioral Methods for Severity Assessment.

It has become mandatory for the application for allowance of animal experimentation to rate the severity of the experimental procedures. In order to minimize suffering related to animal experimentation it is therefore crucial to develop appropriate methods for the assessment of animal suffering. Physiological parameters such as hormones or body weight are used to assess stress in laboratory animals.

Defining mechanisms of neural plasticity after brainstem ischemia in rats.

Objective: Neurological recovery after stroke mainly depends on the location of the lesion. A substantial portion of strokes affects the brainstem. However, patterns of neural plasticity following brainstem ischemia are almost unknown.

Effects of Different Exercise Strategies and Intensities on Memory Performance and Neurogenesis.

It is well established that physical exercise affects both hippocampal neurogenesis and memory functions. Until now, distinctive effects of controlled and voluntary training (VT) on behavior and neurogenesis as well as interactions between exercise intensity, neurogenesis and memory performance are still elusive. The present study tested the impact of moderate controlled and VT on memory formation and hippocampal neurogenesis and evaluated interactions between exercise performance, learning efficiency and proliferation of progenitor cells in the hippocampus.

Targeting Different Monocyte/Macrophage Subsets Has No Impact on Outcome in Experimental Stroke.

Background And Purpose: Peripheral immune cell infiltration contributes to neural injury after ischemic stroke. However, in contrast to lymphocytes and neutrophils, the role of different monocyte/macrophage subsets remains to be clarified. Therefore, we evaluated the effects of selective and unselective monocyte/macrophage depletion and proinflammatory (M1-) and anti-inflammatory (M2-) macrophage transfer on the outcome after experimental cerebral ischemia.

Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis.

It is well known that adult neurogenesis occurs in two distinct regions, the subgranular zone of the dentate gyrus and the subventricular zone along the walls of the lateral ventricles. Until now, the contribution of these newly born neurons to behavior and cognition is still uncertain. The current study tested the functional impacts of diminished hippocampal neurogenesis on emotional and cognitive functions in transgenic Gfap-tk mice.

Combining Growth Factor and Bone Marrow Cell Therapy Induces Bleeding and Alters Immune Response After Stroke in Mice.

Background And Purpose: Bone marrow cell (BMC)-based therapies, either the transplantation of exogenous cells or stimulation of endogenous cells by growth factors like the granulocyte colony-stimulating factor (G-CSF), are considered a promising means of treating stroke. In contrast to large preclinical evidence, however, a recent clinical stroke trial on G-CSF was neutral. We, therefore, aimed to investigate possible synergistic effects of co-administration of G-CSF and BMCs after experimental stroke in mice to enhance the efficacy compared with single treatments.

Functional Improvement after Photothrombotic Stroke in Rats Is Associated with Different Patterns of Dendritic Plasticity after G-CSF Treatment and G-CSF Treatment Combined with Concomitant or Sequential Constraint-Induced Movement Therapy.

We have previously shown that granulocyte-colony stimulating factor (G-CSF) treatment alone, or in combination with constraint movement therapy (CIMT) either sequentially or concomitantly, results in significantly improved sensorimotor recovery after photothrombotic stroke in rats in comparison to untreated control animals. CIMT alone did not result in any significant differences compared to the control group (Diederich et al., Stroke, 2012;43:185-192).

Prevention of an increase in cortical ligand binding to AMPA receptors may represent a novel mechanism of endogenous brain protection by G-CSF after ischemic stroke.

Purpose: Using G-CSF deficient mice we recently demonstrated neuroprotective properties of endogenous G-CSF after ischemic stroke. The present follow-up study was designed to check, whether specific alterations in ligand binding densities of excitatory glutamate or inhibitory GABAA receptors may participate in this effect.

Methods: Three groups of female mice were subjected to 45 minutes of MCAO: wildtype, G-CSF deficient and G-CSF deficient mice substituted with G-CSF.

Progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke.

Background And Purpose: In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia.

Detection of thiol-based redox switch processes in parasites - facts and future.

Malaria and African trypanosomiasis are tropical diseases caused by the protozoa Plasmodium and Trypanosoma, respectively. The parasites undergo complex life cycles in the mammalian host and insect vector, during which they are exposed to oxidative and nitrosative challenges induced by the host immune system and endogenous processes. Attacking the parasite's redox metabolism is a target mechanism of several known antiparasitic drugs and a promising approach to novel drug development.