Biological Markers to Study the Morphological Modifications Induced by Perinatal Asphyxia

Abstract

Statement of the Problem: Perinatal asphyxia (PA), a neurodevelopmental impairment that leads toneonatal mortality and is a determinant factor for short- and long-term disorders. Sincepathophysiological mechanisms triggered by PA are not still totally unveiled, we investigated thechanges in the cytoskeleton organization, synapse, and astrocytes in the nervous tissue.Methodology & Theoretical Orientation: For this study, we used a well-established murine model of PA[1]. After one, 2, 4 and 6 months of severe PA (21 min) rats were sacrificed and their brains wereanalyzed by combining photooxidation, conventional electron microscopy and electron tomography 3-Dreconstruction techniques in two areas hypoxia sensible: neostriatum and hippocampus [1]. Findings:After one month of PA, we found an increase in the F-actin staining in neostriatal and hippocampaldendritic spines together with some filopodia-likes structures, a typical embryonic type of spines inphotooxidated tissue [2] [Fig 1 A). In contrast, after second month of PA, spines were less consistentstained. In addition, we observed an increment of marker for neuronal and glial dysfunction such asGFAP, neurofilament and MAP-2 [3]. These modifications were more clearly defined after 4 months ofPA [3]. After 6 months of PA postsynaptic densities (PSDs) in neostriatum were highly modified. Usingthree-D reconstructions and electron tomography we were able to find clear signs of degeneration in theasphyctic PSDs (Fig 1 B and C) [3]Conclusion & Significance: Therefore, we hypothesize that the cytoskeletal changes induced by PA inthe rat CNS could lead to the severe modifications in synapse and related structures that trigger neuronaldamage. In addition, electron tomography, 3-D reconstruction and photooxidation contributed to dissectcritical alterations generated by PA that are not easily displayed using conventional microscopictechniques. These findings might contribute to generate new therapeutic tools.