Long-Term Impact of Radiation on the Stem Cell and Oligodendrocyte Precursors in the Brain

Background. The cellular basis of long term radiation damage in the brain is not fully understood. Methods and Findings. We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries. Conclusions. This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursor

“One-Size-Fits-All”? Optimizing Treatment Duration for Bacterial Infections

Historically, antibiotic treatment guidelines have aimed to maximize treatment efficacy and minimize toxicity, but have not considered the evolution of antibiotic resistance. Optimizing the duration and dosing of treatment to minimize the duration of symptomatic infection and selection pressure for resistance simultaneously has the potential to extend the useful therapeutic life of these valuable life-saving drugs without compromising the interests of individual patients

Successful radiation treatment of anaplastic thyroid carcinoma metastatic to the right cardiac atrium and ventricle in a pacemaker-dependent patient

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature

Cellular composition characterizing postnatal development and maturation of the mouse brain and spinal cord

The process of development, maturation, and regression in the central nervous system (CNS) are genetically programmed and influenced by environment. Hitherto, most research efforts have focused on either the early development of the CNS or the late changes associated with aging, whereas an important period corresponding to adolescence has been overlooked. In this study, we searched for age-dependent changes in the number of cells that compose the CNS (divided into isocortex, hippocampus, olfactory bulb, cerebellum, ‘rest of the brain’, and spinal cord) and the pituitary gland in 4–40-week-old C57BL6 mice, using the isotropic fractionator method in combination with neuronal nuclear protein as a marker for neuronal cells. We found that all CNS structures, except for the isocortex, increased in mass in the period of 4–15 weeks. Over the same period, the absolute number of neurons significantly increased in the olfactory bulb and cerebellum while non-neuronal cell numbers increased in the ‘rest of the brain’ and isocortex. Along with the gain in body length and weight, the pituitary gland also increased in mass and cell number, the latter correlating well with changes of the brain and spinal cord mass. The majority of the age-dependent alterations (e.g., somatic parameters, relative brain mass, number of pituitary cells, and cellular composition of the cerebellum, isocortex, rest of the brain, and spinal cord) occur rapidly between the 4th and 11th postnatal weeks. This period includes murine adolescence, underscoring the significance of this stage in the postnatal development of the mouse CNS

Fatty Acid and Peptide Profiles in Plasma Membrane and Membrane Rafts of PUFA Supplemented RAW264.7 Macrophages

The eukaryotic cell membrane possesses numerous complex functions, which are essential for life. At this, the composition and the structure of the lipid bilayer are of particular importance. Polyunsaturated fatty acids may modulate the physical properties of biological membranes via alteration of membrane lipid composition affecting numerous physiological processes, e.g. in the immune system. In this systematic study we present fatty acid and peptide profiles of cell membrane and membrane rafts of murine macrophages that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. Using fatty acid composition analysis and mass spectrometry-based peptidome profiling we found that PUFAs from both the n-3 and the n-6 family have an impact on lipid and protein composition of plasma membrane and membrane rafts in a similar manner. In addition, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the unsaturation index of plasma membrane as well as membrane rafts of supplemented cells. With regard to the proposed significance of lipid microdomains for disease development and treatment our study will help to achieve a targeted dietary modulation of immune cell lipid bilayers