Ultrastructural characterization of the Mitochondria-associated membranes abnormalities in human astrocytomas: Functional and therapeutics implications.

Mitochondria-associated membranes (MAMs) are currently considered an intracellular organelle "hot spot" for the intracellular signaling. MAMs are thought to function in cellular energy homeostasis, apoptosis, and calcium signaling. MAM ultrastructure in surgical specimens from human astrocytic neoplasms was studied. Abnormalities in respect to density, length, and width were found. Poorly differentiated glioma like-stem cells deficient in MAM and well-differentiated glioma cells abundant in MAM were observed. This finding could be the structural basis of functional role of MAM linked to some metabolic abnormalities in astrocytic tumors associated to mitochondrial dysfunction and the Warburg effect and their therapeutics implications.

Ultrastructural characterization of macrophage-like mononuclear leukocytes in human astrocytic tumors.

The aim of this study was to describe the ultrastructural features of macrophage-like mononuclear leukocytes associated with human astrocytic tumors. Tumoral biopsies of 10 patients with a pathological diagnosis of astrocytic tumor by means of transmission electron microscopy were examined. The macrophage-like mononuclear leukocyte shows ultrastructural characteristics related with the physiologic phenotype of the alternatively activated macrophage (M2), localized principally around of tumoral vasculature and tumor milieu; classically activated macrophages (M1) in surrounding necrosis areas were observed. The presence of these two ultrastructural kinds of macrophage-like mononuclear leukocytes into different areas of the tumor denotes that cellular response of TAMs is dependent of microenvironment stimuli in different parts of a tumor. The process of transvascular emigration of monocyte/macrophage-like mononuclear leukocytes into tumor is presented. The preponderance of alternatively activated macrophage-like mononuclear leukocytes suggests disequilibrium between pro-tumoral leukocytes and anti-tumoral leukocytes. Therefore, macrophage polarization toward anti-tumoral macrophage-like mononuclear leukocytes would be a potential target for therapeutic manipulation in human astrocytic tumors.

Ultrastructural mitochondrial pathology in human astrocytic tumors: potentials implications pro-therapeutics strategies.

This study was realized to illustrate and analyze the ultrastructural mitochondrial pathology in human astrocytic tumors. Tumoral biopsies of 10 patients with pathological diagnosis of astrocytic tumors by means of transmission electron microscopy were examined. Mitochondria exhibits heterogeneous morphology in all the cases. Mitochondrial swelling with partial or total cristolysis was the most constant alteration observed. Mitochondrial fusion-fission phenomena have been demonstrated. These findings suggest that the majority of astrocytoma cells are incompetent to produce adequate amount of energy by means of oxidative phosphorylation. Ultrastructural mitochondrial pathology indicates that possibly both glycolytic inhibition and inhibition or down-regulation of mitochondrial respiration would be a potential tool for future therapeutic strategies in cases of human astrocytic tumors.

Papel del óxido nítrico en edema cerebral traumático de ratas / Paper of the nitric oxide in traumatic brain edema of rats

El óxido nítrico (NO) es una molécula sencilla que ha sido involucrada en numerosas funciones biológicas, y se piensa participa en algunos procesos patológicos cerebrales, como isquemia y neurotoxicidad. El presente estudio fue diseñado para evaluar si existen modificaciones en los niveles de NO en el edema cerebral vasogénico. Se utilizaron ratas Sprague-Dawley de 4 a 5 semanas de nacidas, a quienes se les provocó injuria por frío, como modelo de trauma cerebral, en el hemisferio cerebral derecho, tomando el izquierdo como control. Los niveles de NO fueron medidos como su producto de degradación, NO2, a través del ensayo de diazotización, a las 2 horas y a las 24 horas de provocado el trauma. Se realizó análisis histológico, con coloración hematoxilina-eosina. La significación estadística fue evaluada a través de la "t de Student". A las 2 horas, los niveles de óxido nítrico en el hemisferio cerebral derecho se encontraron elevados significativamente con respecto a los del hemisferio contralateral (26.46 por ciento, p<0.01). El L-NAME fue capaz de inhibir significativamente la actividad de la NOS en el hemisferio donde se provocó el edema (31.78 por ciento), pero no tuvo efecto sobre el hemisferio control. A las 24 horas, los niveles de NO no difirieron significativamente entre ambos hemisferios. Ninguna variación fue encontrada cuando se trataron estos tejidos con L-NAME. El análisis microscópico reveló edema cerebral en el hemisferio derecho, y un hemisferio izquierdo normal. Los niveles de NO se encuentran aumentados en las etapas tempranas de la formación del edema cerebral vasogénico. Este hallazgo indica su probable participación en los estados iniciales de la patogénesis de este tipo de edema