Blocking of Connexin-Mediated Communication Promotes Neuroprotection during Acute Degeneration Induced by Mechanical Trauma

Accruing evidence indicates that connexin (Cx) channels in the gap junctions (GJ) are involved in neurodegeneration after injury. However, studies using KO animal models endowed apparently contradictory results in relation to the role of coupling in neuroprotection. We analyzed the role of Cx-mediated communication in a focal lesion induced by mechanical trauma of the retina, a model that allows spatial and temporal definition of the lesion with high reproducibility, permitting visualization of the focus, penumbra and adjacent areas. Cx36 and Cx43 exhibited distinct gene expression and protein levels throughout the neurodegeneration progress. Cx36 was observed close to TUNEL-positive nuclei, revealing the presence of this protein surrounding apoptotic cells. The functional role of cell coupling was assessed employing GJ blockers and openers combined with lactate dehydrogenase (LDH) assay, a direct method for evaluating cell death/viability. Carbenoxolone (CBX), a broad-spectrum GJ blocker, reduced LDH release after 4 hours, whereas quinine, a Cx36-channel specific blocker, decreased LDH release as early as 1 hour after lesion. Furthermore, analysis of dying cell distribution confirmed that the use of GJ blockers reduced apoptosis spread. Accordingly, blockade of GJ communication during neurodegeneration with quinine, but not CBX, caused downregulation of initial and effector caspases. To summarize, we observed specific changes in Cx gene expression and protein distribution during the progress of retinal degeneration, indicating the participation of these elements in acute neurodegeneration processes. More importantly, our results revealed that direct control of GJ channels permeability may take part in reliable neuroprotection strategies aimed to rapid, fast treatment of mechanical trauma in the retina.

Analysis of elastic functionally graded materials under large displacements via high-order tetrahedral elements

The purpose of this study is to present a position based tetrahedral finite element method of any order to accurately predict the mechanical behavior of solids constituted by functionally graded elastic materials and subjected to large displacements. The application of high-order elements makes it possible to overcome the volumetric and shear locking that appears in usual homogeneous isotropic situations or even in non-homogeneous cases developing small or large displacements. The use of parallel processing to improve the computational efficiency, allows employing high-order elements instead of low-order ones with reduced integration techniques or strain enhancements. The Green-Lagrange strain is adopted and the constitutive relation is the functionally graded Saint Venant-Kirchhoff law. The equilibrium is achieved by the minimum total potential energy principle. Examples of large displacement problems are presented and results confirm the locking free behavior of high-order elements for non-homogeneous materials. (C) 2011 Elsevier B.V. All rights reserved.