Our results offer evidence that IPostC mediates cardioprotection in the remodeled rat myocardium primarily via activation of the PI3K-PKB/Akt reperfusion injury salvage kinase pathway.

Monoclonal antibodies (mAbs), immunoglobulin fragments, and other proteins are important scaffolds in the development of radiopharmaceuticals for diagnostic immuno-positron emission tomography (immuno-PET) and targeted radioimmunotherapy (RIT). Conventional methods for radiolabelling proteins with metal ions such as 68Ga, 64Cu, 89Zr, and 90Y require multi-step procedures involving pre-purification, functionalisation with a chelate, and subsequent radiolabelling. Standard coupling chemistries are time-consuming, difficult to automate, and involve synthesis, isolation, and storage of an intermediate, new molecular entity (the conjugated mAb) whose biochemical properties can differ from those of the parent protein. To circumvent these issues, we developed a photoradiochemical approach that uses fast, chemoselective, light-induced protein modification under mild conditions with novel metal-ion-binding chelates derivatised with aryl azide (ArN3) groups. Experiments show that one-pot photochemical conjugation and radiolabelling of formulated mAbs can be achieved in <20 min.

Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.

Current implantation formats to deliver bone marrow-derived mesenchymal stem cells (MSCs) to the site of myocardial injury resulted only in limited cell retention and integration. As an alternative concept to single cell transplantation, we investigated the fate of cell tracker-labeled syngenic rat MSC microtissue implants, injected into the scar area in a chronic rat myocardial infarction model. Analysis of the explants after 2 and 7 days revealed substantial amounts of the cell tracker within the infarct region. However, the signal was associated with the extracellular matrix rather than with viable implanted cells. Following these results, we systematically evaluated the behavior of MSCs derived from mouse, rat and human origin in the microtissue format in vitro. We found that MSC-composed microtissues of all three species displayed highly elevated levels of apoptotic activity and cell death. This effect could be attenuated by initiating osteogenic differentiation during the tissue formation process. We conclude that MSCs used for tissue regeneration undergo apoptosis in their new environment unless they get appropriate signals for differentiation that permit sustained survival. These findings may explain the limited cellular regeneration potential in current MSC-based clinical trials and may change therapeutic strategies away from pure, un-modulated cell delivery concepts. Current implantation formats to deliver bone marrow-derived mesenchymal stem cells (MSCs) to the site of myocardial injury resulted only in limited cell retention and integration. As an alternative concept to single cell transplantation, we investigated the fate of cell tracker-labeled syngenic rat MSC microtissue implants, injected into the scar area in a chronic rat myocardial infarction model. Analysis of the explants after 2 and 7 days revealed substantial amounts of the cell tracker within the infarct region. However, the signal was associated with the extracellular matrix rather than with viable implanted cells. Following these results, we systematically evaluated the behavior of MSCs derived from mouse, rat, and human origin in the microtissue format in vitro.We found that MSC-composed microtissues of all three species displayed highly elevated levels of apoptotic activity and cell death. This effect could be attenuated by initiating osteogenic differentiation during the tissue formation process. We conclude that MSCs used for tissue regeneration undergo apoptosis in their new environment unless they get appropriate signals for differentiation that permit sustained survival. These findings may explain the limited cellular regeneration potential in current MSC-based clinical trials and may change therapeutic strategies away from pure, unmodulated cell delivery concepts.

BackgroundRabbits are widely accepted as an animal model in neuroscience research. They also represent very popular pet animals, and, in selected clinical cases with neurological signs, magnetic resonance imaging (MRI) may be indicated for imaging the rabbit brain. Literature on the normal MRI anatomy of the rabbit brain and associated structures as well as related reference values is sparse. Therefore, it was the purpose of this study to generate an MRI atlas of the normal rabbit brain including the pituitary gland, the cranial nerves and major vessels by the use of a 3 T magnet.ResultsBased on transverse, dorsal and sagittal T2-weighted (T2w) and pre- and post-contrast 3D T1-weighted (T1w) sequences, 60 intracranial structures were identified and labeled. Typical features of a lissencephalic brain type were described. In the 5 investigated rabbits, on T1w images a crescent-shaped hyperintense area caudodorsally in the pituitary gland most likely corresponded to a part of the neurohypophysis. The optic, trigeminal, and in part, the facial, vestibulocochlear and trochlear nerves were identified. Mild contrast enhancement of the trigeminal nerve was present in all rabbits. Absolute and relative size of the pituitary gland, midline area of the cranial and caudal cranial fossa and height of the tel- and diencephalon, 3rd and 4th ventricles were also determined.ConclusionsThese data established normal MRI appearance and measurements of the rabbit brain. Results provide reference for research studies in rabbits and, in rare instances, clinical cases in veterinary medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13028-015-0139-6) contains supplementary material, which is available to authorized users.