Response of the rat spinal cord to X-ray microbeams

BACKGROUND AND PURPOSE: To quantify the late dose-related responses of the rat cervical spinal cord to X-ray irradiations by an array of microbeams or by a single millimeter beam. MATERIALS AND METHODS: Necks of anesthetized rats were irradiated transversely by an 11mm wide array of 52 parallel, 35μm wide, vertical X-ray microbeams, separated by 210μm intervals between centers. Comparison was made with rats irradiated with a 1.35mm wide single beam of similar X-rays. Rats were killed when paresis developed, or up to 383days post irradiation (dpi). RESULTS: Microbeam peak/valley doses of ≈357/12.7Gy to 715/25.4Gy to an 11mm long segment of the spinal cord, or single beam doses of ≈146-454Gy to a 1.35mm long segment caused foreleg paresis and histopathologically verified spinal cord damage; rats exposed to peak/valley doses up to 253/9Gy were paresis-free at 383dpi. CONCLUSIONS: Whereas microbeam radiation therapy [MRT] for malignant gliomas implanted in rat brains can be safe, palliative or curative, the high tolerance of normal rat spinal cords to similar microbeam exposures justifies testing MRT for autochthonous malignancies in the central nervous system of larger animals with a view to subsequent clinical applications.

Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy

Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.

Assessment of the mineral density and mineral content of the equine third metacarpal and first phalanx bone by dual energy x-ray absorptiometry

In the first part of this methodological study eleven metacarpi of 9 skeletally normal horses were examined from 4 directions by dual energy x-ray absorptiometry (DXA). The differences between the dorsopalmar-palmarodorsal and lateromedial-mediolateral (opposite sites) bone mineral density (BMD) values were found to be nonsignificant. In the second part of the study the precision of the Norland XR-26 densitometer was tested by measuring 34 metacarpal bones and 34 proximal phalanges, each of them three times, from a single direction. The difference between the individual measurements of the first phalanges and of the metacarpal bones originating from the right or the left side of the same horse were not significant, nor did the age or breed have a significant effect on BMD or bone mineral content (BMC). However, both BMD and BMC are greater in the metacarpal bones than in the proximal phalanges and are higher in geldings than in mares or to stallions, while the BMD or BMC values of mares and stallions did not differ from each other significantly. These data point to the necessity of further BMD studies in a higher number of patients.

Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane

Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.

X-ray phase contrast imaging of metallized and non-metallized biological samples

Imaging of biological samples has been performed with a variety of techniques for example electromagnetic waves, electrons, neutrons, ultrasound and X-rays. Also conventional X-ray imaging represents the basis of medical diagnostic imaging, it remains of limited use in this application because it is based solely on the differential absorption of X-rays by tissues. Coherent and bright photon beams, such as those produced by third-generation synchrotron X-ray sources, provide further information on subtle X-ray phase changes at matter interfaces. This complements conventional X-ray absorption by edge enhancement phenomena. Thus, phase contrast imaging has the potential to improve the detection of structures on images by detecting those structures that are invisible with X-ray absorption imaging. Images of a weakly absorbing nylon fibre were recorded in in-line holography geometry using a high resolution low-noise CCD camera at the ESRF in Grenoble. The method was also applied to improve image contrast for images of biological tissues. This paper presents phase contrast microradiographs of vascular tree casts and images of a housefly. These reveal very fine structures, that remain invisible with conventional absorption contrast only.

Post-mortem radiological CT identification based on classical ante-mortem X-ray examinations

Radiological identification is important in forensic medicine. Identification using comparison of individualising structures with ante- and post-mortem conventional radiographs has been known for a long time. New radiological procedures such as computed tomography (CT) and magnetic resonance imaging (MRI) are being increasingly used for identification. In this paper, a new comparative approach using various radiological methods is described and its application demonstrated. This new approach is the comparison of ante-mortem conventional radiographs with projected images calculated from post-mortem CT data. The identification procedure will be illustrated with reference to the frontal sinus and the pelvis.