Antioxidant and Protective Mechanisms against Hypoxia and Hypoglycaemia in Cortical Neurons in Vitro

Abstract

In the present work, we have studied whether cell death could be induced in cortical neurons from rats subjected to different period of O2 deprivation and low glucose (ODLG). This “in vitro” model is designed to emulate the penumbra area under ischemia. In these conditions, cortical neurons displayed loss of mitochondrial respiratory ability however, nor necrosis neither apoptosis occurred despite ROS production. The absence of cellular death could be a consequence of increased antioxidant responses such as superoxide dismutase-1 (SOD1) and GPX3. In addition, the levels of reduced glutathione were augmented and HIF-1/3α overexpressed. After long periods of ODLG (12–24 h) cortical neurons showed cellular and mitochondrial membrane alterations and did not recuperate cellular viability during reperfusion. This could mean that therapies directed toward prevention of cellular and mitochondrial membrane imbalance or cell death through mechanisms other than necrosis or apoptosis, like authophagy, may be a way to prevent ODLG damage.

Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia

“…To elucidate the underlying mechanism regulating BBB permeability during hypoglycemia and the potential role of exogenous VEGF in protecting brain endothelial cells against hypoglycemia, we established an in vitro BBB model using mouse brain microvascular endothelial cells (bEnd.3) which were cultured in normal glucose (5.5 mM glucose) or low glucose (0, 0.5, or 1 mM glucose) for varying times. This was done in the hope of mimicking clinical hypoglycemia conditions, considering that brain glucose concentrations approaches zero when blood glucose concentrations falls below 2 mM (Choi et al 2001 ), and within 24 h of hypoglycemic duration was used in many studies (Merino et al 2014 ; Sajja et al 2014 ).…”

Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma

“…One way that cells remove ROS is by producing proteins such as glutathione and metallothionein that bind to ROS and form more hydrophilic compounds that are easily excreted through Glutathione S-transferases [ 9 ] . Copper and zinc-containing superoxide dismutase, (Cu/Zn- cytoplasmic enzyme (SOD-1) metabolizes superoxide radicals to molecular oxygen and hydrogen peroxide, providing defense against oxygen toxicity [ 9 , 10 , 11 ] . For this reason, there is a need to establish whether the Hg from dental amalgam fillings can increase heavy metal release and affect glutathione or SOD-1 activity as compensatory mechanism in patients (women).…”

Mitochondrial Dysfunction and Changes in High-Energy Compounds in Different Cellular Models Associated to Hypoxia: Implication to Schizophrenia

“…Curiously, gaseous hypoxia in SHR astrocytes decreased DCF signal. In this case, it is hypothesized that a severe hypoxia could modify the redox homeostasis leading the cell to a metabolically collapse, decreasing the DCF signal 80–82 . Alternatively, it can induce an increase in antioxidant capacity, which would decrease ROS.…”

“…However, after gaseous hypoxia, we only observed an increase in Mitosox fluorescence in Wistar cells after 18 and 24 hours, and after 18 hours in SHR groups. The drastic reduction of Mitosox after 24 hours of gaseous hypoxia, can be due to modifications in redox metabolism after long periods of hypoxia (intrauterine) 81,82 or, alternatively, to a mitochondrial destabilization and even metabolic collapse, that could in part, explain the less superoxide synthesis 82,83 .…”