Dietary supplementation with tBHQ, an Nrf2 stabilizer molecule, confers neuroprotection against apoptosis in amyloid ß-injected rat.

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. Considering the protective role of Nrf2 against oxidative injury, we studied to determine whether in vivo toxicity of amyloid ß (Aß) can be attenuated by tBHQ, an Nrf2 stabilizer, Using an Aß injection model. We demonstrated that pre-activation of endogenous Nrf2 by tBHQ attenuated Aß-induced caspase-3 expression. tBHQ enhanced GSH, decreased MDA level, and inhibited NF-κB. This investigation provides the first documentation of tBHQ's neuroprotective effect through decrease of Aß accumulation in rat brain. Our results show the involvement of Hsp-70 in this protective effect. In summary tBHQ treatment for 1 week prior to Aß injection protected against the oxidative damage, apoptosis and Aß accumulation in rats.

Acute 17ß-estradiol pretreatment protects against abdominal aortic occlusion induced spinal cord ischemic-reperfusion injury.

Postoperative neurologic deficit due to spinal cord ischemia-reperfusion (I/R) injury is the most devastating complication following thoracoabdominal aortic aneurysm repairs. The protective potential for 17ß-Estradiol has not been yet studied in such injury. In this study, ischemia induction for 18 min in male New Zealand White rabbits resulted in the highest percentage (80%) of biphasic paraplegic outcome assessed by Tarlov's score. Acute Estradiol pretreatment (1 mg/kg, i.p., 30 min before I/R induction) altered this outcome and significantly prevented the worsening pattern of neurologic deficits over 48 h of observation. Histopathologic and oxidative stress evaluations of lumbar spinal cords taken in delayed permanent paraplegic phase (48 h after ischemia induction), further confirmed protective efficacy of Estradiol in such context. In western blot analysis, the expression of cleaved caspase-3 and heat shock protein 70 declined in Estradiol pretreated group compared to ischemic control group. TUNEL assay also showed the efficacy of Estradiol to abate motor neuron apoptosis. Interestingly, Estradiol respectively increased and decreased the expression of Cyclooxygenase (COX)-1 and COX-2, to a significant extent. Estradiol, exerting its protection through affecting one or a combination of involved biochemical factors can constitute a potential candidate to protect against thoracoabdominal aortic aneurysm repairs induced spinal cord I/R injury.

Comparing two teaching methods based on concept map and lecture on the level of learning in basic life support.

Education and training about Basic Life Support is necessary for different medical groups such as nurses. Different teaching methods have been developed to preserve essential medical information, knowledge and skills. The purpose of the study was to determine the effect of concept map-based and lecture-based teaching methods on the level of nursing students' learning in Basic Life Support. This quasi-experimental study was conducted in 2015 on 57 nursing students from a nursing school in Tehran. Students were selected by census and then divided into lecture (n = 29) and concept map groups (n = 28) by random allocation. The effect of education on knowledge (before, immediately after, one week after and one month after session) and practice (before and immediately after session) was studied. No significant differences were found between the mean scores of knowledge and practice before intervention (P > 0.05). After intervention the mean scores of knowledge were not statistically significant between the two groups (P > 0.05) but mean scores of practice were significantly higher in the concept map group (P = 0.03). In achieving skill and practice goals, it seems that the concept map-based teaching method was more effective than the lecture method.

Time course study of Aß formation and neurite outgrowth disruption in differentiated human neuroblastoma cells exposed to H2O2: protective role of autophagy.

Here, we tried to elucidate the possible role of autophagy against H2O2 and Amyloid beta (Aß) induced neurotoxicity using retinoic acid differentiated SH-SY5Y cells. We found that H2O2 disrupted neurite outgrowth concomitant with production of Aß. Furthermore, we showed that H2O2 could increase the apoptotic factors such as Bax/Bcl-2 ratio, caspase-3 level, and PARP activity in a time course manner. These findings were confirmed by acridine orange/ethidium bromide and Hoechst staining. In addition, we observed that H2O2 led to conversion of LC3 protein from LC3I to LC3II and an increase in autophagy flux. Autophagy factors including LC3B, Atg7, and Atg12 increased and reached their highest level after 2h of insulting and then dropped to a lower level. Our results showed that autophagy could internalize and degrade intra- and extracellular Aß after 3h treatment with H2O2. However, the remaining amount of Aß accelerated morphological atrophy and, as a result, increased neuronal death (apoptosis). Inhibition of autophagy influx, using 3-methyl-adenine, increased intra- and extracellular levels of Aß, providing more proof for a protective role of autophagy against oxidative stress. Further studies can shed light on the important role of autophagy by finding new pathways involved in Aß degeneration.

A quantitative assay for the monitoring of autophagosome accumulation in different phases of the cell cycle.

Macroautophagy is a process accompanied by the formation of double-membrane vesicles known as autophagosomes. Although in recently published reviews various methods for the detection of autophagosomes were described, a reliable technique for the automated quantitative evaluation of autophagosome accumulation is still lacking. Here we developed a new assay which is based on the fact that the number of autophagosomes is correlated with the amount of the LC3-II protein, which is specifically associated with autophagosomal membranes. Monitoring of autophagosome: accumulation was performed by extracting the membrane-unbound LC3-I form of the protein from cells, followed by flow cytometric detection of the autophagosomal membrane-associated fraction of LC3-II. This assay could be used for monitoring autophagosomes by flow cytometry utilizing immunostaining with the antibody against the LC3 protein. It is also suitable for analysis of: cells expressing GFP-LC3. We showed that co-staining with propidium iodide allows detection of basal level of autophagosomes in different phases of the cell cycle. Autophagy activators, such as: rapamycin or cell starvation, were able to induce accumulation of autophagosomes in G0/G1, S and G2/M phases. Thus, utilization of this assay simplifies monitoring of autophagosome accumulation induced by different activators or inhibitors of macroautophagy and it is suggested as being useful in the detection of autophagosomes in different phases of the cell cycle.

Cyclooxygenase (COX)-1 activity precedes the COX-2 induction in Aß-induced neuroinflammation.

Two different isoforms of cyclooxygenases, COX-1 and COX-2, are constitutively expressed under normal physiological conditions of the central nervous system, and accumulating data indicate that both isoforms may be involved in different pathological conditions. However, the distinct role of COX-1 and COX-2 and the probable interaction between them in neuroinflammatory conditions associated with Alzheimer's disease are conflicting issues. The aim of this study was to elucidate the comparable role of each COX isoform in neuroinflammatory response induced by ß-amyloid peptide (Aß). Using histological and biochemical methods, 13 days after stereotaxic injection of Aß into the rat prefrontal cortex, hippocampal neuroinflammation and neuronal injury were confirmed by increased expression of tumor necrosis factor-alpha (TNF-α) and COX-2, elevated levels of prostaglandin E2 (PGE2), astrogliosis, activation of caspase-3, and neuronal cell loss. Selective COX-1 or COX-2 inhibitors, SC560 and NS398, respectively, were chronically used to explore the role of COX-1 and COX-2. Treatment with either COX-1 or COX-2 selective inhibitor or their combination equally decreased the level of TNF-α, PGE2, and cleaved caspase-3 and attenuated astrogliosis and neuronal cell loss. Interestingly, treatment with COX-1 selective inhibitor or the combined COX inhibitors prevented the induction of COX-2. These results indicate that the activity of both isoforms is detrimental in neuroinflammatory conditions associated with Aß, but COX-1 activity is necessary for COX-2 induction and COX-2 activity seems to be the main source of PGE2 increment.

Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity.

The protective effect of tomato extract and lycopene on acute doxorubicin (DOX) myocardial toxicity was evaluated in mice. DOX toxicity, induced by a single intraperitoneal injection (15 mg/kg), was revealed by an elevated serum CPK(MB) and histopathological observations. Tomato extract (1.2 and 2.4 g/kg, i.p.) and lycopene (1.7 and 3.5 mg/kg, i.p.) prevented the rise in serum CPK(MB) and ameliorated cardiac cell injury. These results suggest that tomato extract and lycopene inhibit DOX cardiotoxicity and might serve as a novel combination chemotherapeutic agent with DOX to limit free radical-mediated organ injury.