Asymmetric Cell–Matrix and Biomechanical Abnormalities in Elastin Insufficiency Induced Aortopathy

Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln ^+/? ) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln ^+/? ) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln ^+/? aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln ^+/? aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln ^+/? ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure–function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.     

Orbital volume and surface after Le Fort III advancement in syndromic craniosynostosis

There are no quantitative standards for the volumetric measurements of the orbital cavity after Le Fort III advancement. Computed tomography (CT) scan images have given the opportunity to compare with accuracy the real anatomic changes and potentially the functional improvements that resulted after a surgical treatment.Three-dimensional CT scan images processed by DICOM files in Dolphin 3D Software were used to assess orbital volume and surface in 12 subjects affected by craniofacial syndromic malformations treated with Le Fort III advancement. The preoperative (T0) and postoperative (T1: 6 months after surgery) three-dimensional craniofacial CT scans of the subjects were collected and retrospectively analyzed. Image segmentation of the anatomic orbital cavity and the three-dimensional graphic rendering were done by using the Dolphin Imaging Plus 11.0 software.The orbital volume was increased after surgery, with statistical significance, from 22,267 to 22,706.3 mm(3) in the right eye and from 26,511 mm(3) to 26,256.4 mm(3) in the left eye. The surface of both bony orbits had an expansion, which is statistically significant. In conclusion, this study showed that the orbital advancement in white subjects after Le Fort III advancement was significant and produced a significant augmentation of the orbital volume and surface area with correction of the ocular bulb proptosis.     

Selective activation of protein kinase C∊ in mitochondria is neuroprotective in vitro and reduces focal ischemic brain injury in mice

Activation of protein kinase C? (PKC?) confers protection against neuronal ischemia/reperfusion. Activation of PKC? leads to its translocation to multiple intracellular sites, so a mitochondria‐selective PKC? activator was used to test the importance of mitochondrial activation to the neuroprotective effect of PKC?. PKC? can regulate key cytoprotective mitochondrial functions, including electron transport chain activity, reactive oxygen species (ROS) generation, mitochondrial permeability transition, and detoxification of reactive aldehydes. We tested the ability of mitochondria‐selective activation of PKC? to protect primary brain cell cultures or mice subjected to ischemic stroke. Pretreatment with either general PKC? activator peptide, TAT‐Ψ?RACK, or mitochondrial‐selective PKC? activator, TAT‐Ψ?HSP90, reduced cell death induced by simulated ischemia/reperfusion in neurons, astrocytes, and mixed neuronal cultures. The protective effects of both TAT‐Ψ?RACK and TAT‐Ψ?HSP90 were blocked by the PKC? antagonist ?V_1–2, indicating that protection requires PKC? interaction with its anchoring protein, TAT‐?RACK. Further supporting a mitochondrial mechanism for PKC?, neuroprotection by TAT‐Ψ?HSP90 was associated with a marked delay in mitochondrial membrane depolarization and significantly attenuated ROS generation during ischemia. Importantly, TAT‐Ψ?HSP90 reduced infarct size and reduced neurological deficit in C57/BL6 mice subjected to middle cerebral artery occlusion and 24 hr of reperfusion. Thus selective activation of mitochondrial PKC? preserves mitochondrial function in vitro and improves outcome in vivo, suggesting potential therapeutic value clinically when brain ischemia is anticipated, including neurosurgery and cardiac surgery. © 2013 Wiley Periodicals, Inc.     

Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations

As well as consolidating memory, sleep has been proposed to serve a second important function for memory, i.e. to free capacities for the learning of new information during succeeding wakefulness. The slow wave activity (SWA) that is a hallmark of slow wave sleep could be involved in both functions. Here, we aimed to demonstrate a causative role for SWA in enhancing the capacity for encoding of information during subsequent wakefulness, using transcranial slow oscillation stimulation (tSOS) oscillating at 0.75 Hz to induce SWA in healthy humans during an afternoon nap. Encoding following the nap was tested for hippocampus‐dependent declarative materials (pictures, word pairs, and word lists) and procedural skills (finger sequence tapping). As compared with a sham stimulation control condition, tSOS during the nap enhanced SWA and significantly improved subsequent encoding on all three declarative tasks (picture recognition, cued recall of word pairs, and free recall of word lists), whereas procedural finger sequence tapping skill was not affected. Our results indicate that sleep SWA enhances the capacity for encoding of declarative materials, possibly by down‐scaling hippocampal synaptic networks that were potentiated towards saturation during the preceding period of wakefulness.