Hyperglycemia increases superoxide production in the CA1 pyramidal neurons after global cerebral ischemia.
ABSTRACT Transient global cerebral ischemia results in selective neuronal death in the vulnerable hippocampal CA1 pyramidal neurons in a delayed manner. Hyperglycemia accelerates and exacerbates neuronal damage in this region. The object of this study was to determine whether hyperglycemia-enhanced damage is associated with increased production of superoxide anion after ischemia. The results showed that hyperglycemic ischemia caused a significant increase of superoxide production in the hippocampal CA1 neurons compared to normoglycemic animals after 18 h of recirculation, suggesting that enhanced superoxide anion production may mediate the hyperglycemia-accelerated and -enhanced neuronal death in the hippocampal CA1 area after ischemia and reperfusion.
- SourceAvailable from: Dominic P D'Agostino
[Show abstract] [Hide abstract]
- "Several methods of ROS detection exist, but the most accurate and sensitive method for detecting intracellular ROS in cells and tissues involves fluorescence-based techniques (Budd et al. 1997; Castilho et al. 1999; Gomes et al. 2005; Zuo and Clanton 2002). The fluorogenic probe most commonly used for intracellular ⅐O 2 Ϫ detection is DHE, and it has been extensively used to measure intracellular ⅐O 2 Ϫ in the hippocampus (Bindokas et al. 1996; Kawase et al. 1999; Kovacs et al. 2001; Muranyi and Li 2006; Peterson et al. 2002). "
ABSTRACT: Neuronal signaling, plasticity, and pathologies in CA1 hippocampal neurons are all intimately related to the redox environment and, thus tissue oxygenation. This study tests the hypothesis that hyperoxic superfusate (95% O(2)) causes a time-dependent increase in superoxide anion (*O(2)(-)) production in CA1 neurons in slices, which will decrease as oxygen concentration is decreased. Hippocampal slices (400 microm) from weaned rats were incubated with the fluorescent probe dihydroethidium (DHE), which detects intracellular *O(2)(-) production. Slices were loaded for 30 min using 10 microM DHE and maintained using one-sided superfusion or continuously loaded using 2.5 microM DHE and maintained using two-sided superfusion (36 degrees C). Continuous loading of DHE and two-sided superfusion gave the highest temporal resolution measurements of *O(2)(-) production, which was estimated by the increase in fluorescence intensity units (FIUs) per minute (FIU/min +/- SE) over 4 h. Superoxide production (2.5 microM DHE, 2-sided superfusion) was greatest in 95% O(2) (6.6 +/- 0.4 FIU/min) and decreased significantly during co-exposure with antioxidants (100 microM melatonin, 25 microM MnTMPyP) and lower levels of O(2) (60, 40, and 20% O(2) at 5.3 +/- 0.3, 3.3 +/- 0.1, and 1.6 +/- 0.2 FIU/min, respectively). CA1 cell death after 4 h (ethidium homodimer-1 staining) was greatest in 95% O(2) and lowest in 40 and 20% O(2). CA1 neurons generated evoked action potentials in 20% O(2) for >4 h, indicating viability at lower levels of oxygenation. We conclude that .O(2)(-) production and cell death in CA1 neurons increases in response to increasing oxygen concentration product (= PO(2) x time). Additionally, lower levels of oxygen (20-40%) and antioxidants should be considered to minimize superoxide-induced oxidative stress in brain slices.Journal of Neurophysiology 08/2007; 98(2):1030-41. DOI:10.1152/jn.01003.2006 · 3.04 Impact Factor
[Show abstract] [Hide abstract]
- "However, the existence of direct pro-oxidant effects of the carbohydrates not efficiently counterbalanced by antioxidant compounds cannot be excluded (Busserolles et al., 2002; Vincent et al., 2004; Beauquis et al., 2006). Actually, it has been demonstrated that hyperglycemia of long duration, as observed in glucose-infused animals and in experimental diabetes , enhanced and accelerated neuronal damage induced by transient experimental hypoxia or focal cerebral ischemia and facilitated the induction of seizures (Smith et al., 1984; Li et al., 1998; Muranyi and Li, 2006). In fact, hyperglycemia in these hypoxic conditions increased both the formation of reactive oxygen species and mitochondrial dysfunction, and activated neuronal death pathways in accordance with an increased loss of neurons in several brain regions, including the hippocampal formation (Ding et al., 2004; Shi and Liu, 2006). "
ABSTRACT: Aims:Chronicethanolconsumptionleadstooxidativedamageinthecentralnervoussysteminducingneuronaldegeneration and impairment of brain functions. Nevertheless, it has been reported that grape polyphenols might prevent the alluded ethanol effects. We have reported that prolonged red wine intake improves hippocampal formation oxidative status, a finding not replicated using Port wine. Thus, we thought of interest to compare the effects of chronic ingestion of these wines in the morphology of dentate gyrus (DG) neurons that are particularly vulnerable to alcohol effects. Methods: Six-month-old Wistar rats were fed either with red wine or Port wine (both with 20% ethanol content, v/v), and the results were compared with 20% (v/v) ethanol-treated, ethanol/glucose and pair-fed control groups. After 6 months of treatment, the layer volumes of the DG and the total number of granule and hilar neurons were estimated. The dendritic trees of granule cells were also studied in Golgi-impregnated material. Results: The number of granule cells and the DG layer volumes were similar among all groups. However, the number of hilar neurons was reduced in Port wine, ethanol-treated and ethanol/glucose animals. Furthermore, the granule cells from these groups showed a decrease in the total dendritic length. Conclusions: Although the Port wine and red wine have similar amounts of flavanols with identical ability to protect against oxidative stress, the differences observed are probably related to the very dissimilar processes of wine production, leading in Port wine to a high content of sugars, which are known to have potent pro-oxidant effects.
- [Show abstract] [Hide abstract]
ABSTRACT: Reduced supply of glucose involves in many pathological conditions such as stroke and contributes to ischemic injuries. In contrast, hyperglycemia has also been regarded as an important factor in causing and exaggerating stroke damage. Although the molecular mechanism(s) of imbalanced glucose-induced cellular injuries under low oxygen conditions are not clear, oxidative stress has been implicated in both hypo- and hypeglycemic damage. Redox status is critical for the regulation of cellular signaling and cell survival. The effects of glucose levels on redox status are not well understood in neurons under hypoxia. The purpose of this study was to determine the effects of glucose concentration on the redox status of rat primary neurons under hypoxia. The cellular redox status was determined from GSH/GSSG ratios, and oxidation of 2,3-dichlorofluorscein diacetate was used to assess levels of reactive oxygen species (ROS). We found that glucose levels were critical in regulating redox state in these neurons under hypoxia. The results showed that under hypoxic conditions: (1) there was an optimal glucose concentration (25mM) at which neurons maintained a reducing environment and showed the lowest levels of ROS and cell death; (2) in the concentration range of 0-25mM, the presence of glucose increased cellular GSH/GSSG ratio and reduced ROS and cell death; and (3) over-supply of glucose (25-100mM) elevated ROS levels, produced an oxidizing environment, and increased cell death. These results suggest that cellular redox status regulated by glucose may play an important role in glucose-mediated cellular responses in hypoxia.Neuroscience Letters 01/2007; 410(1):57-61. DOI:10.1016/j.neulet.2006.09.066 · 2.06 Impact Factor