Neuroprotective effects of gamma-glutamylcysteine ethyl ester on an in vivo moderate traumatic brain injury-mediated model and in vitro in cortical astrocytes and neurons

Neurodegeneration is the loss of neuronal structures or functions, while neuroprotection is the delay or prevention of neurodegeneration. In traumatic brain injury (TBI), neurodegeneration can occur as the result of oxidative stress, the imbalance of oxidants and antioxidants levels; therefore, antioxidant approaches can be effective therapeutic methods for neuroprotection by attenuating oxidative stress. Glutathione (GSH), a naturally occurring antioxidant, plays an important role in the maintenance of intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this thesis, we attempted to evaluate the abilities of a GSH precursor, gamma-glutamylcysteine ethyl ester (GCEE), to prevent neurodegeneration by combating intracellular oxidative stress in neurons and astrocytes. For in vivo experiments, controlled cortical impact (CCI) was performed on Wistar rats to simulate moderate TBI, and GCEE (150 mg/kg) or saline was administrated 30 min or 60 min after the brain injury. Fluoro Jade-B (FJB), an ionic fluorescein derivate, was adapted to selectively stain the degenerating neurons on the brain tissues, and FJB-positive neurons were quantified. Administration of GCEE (150 mg/kg) post- injury decreased the number of FJB positive neurons that were significantly increased in saline treated groups. Next, the protective roles of GCEE in vitro in rat primary cortical astrocytes were investigated using various concentrations of tert-butyl hydroperoxide (tBHP) in order to induce oxidative stress and further toxicity. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The status of oxidative stress was determined by measuring intracellular ROS levels through dichlorofluorescein (DCF) assay. GCEE restored cell viability that was significantly decreased in untreated cells by decreasing oxidative stress. Lastly, the antioxidant properties of GCEE in neurons and astrocytes were investigated in a time-dependent manner. GCEE was able to immediately attenuate intracellular oxidative stress both in neurons and astrocytes. Such decreased oxidative stress was progressively increased in neurons, whereas decreased oxidative stress remained in astrocytes. Overall, our current findings suggest the protective roles of GCEE in both neurons and astrocytes may contribute to the potential therapeutic effects on oxidative stress-associated neurodegeneration following traumatic brain injury

Exploring the effects of contextual factors on home lighting experience

Background Although lighting increasingly penetrates our everyday life due to technology advancement, little is known about how people interact with lighting and how contextual factors impact on the experience. Thus, this study attempted to reveal how two contextual factors (the level of concentration required for pleasant lighting use and social interaction) could influence the manipulation of lighting parameters, particularly focusing on the major factors of lighting such as illuminance, color temperature, and hue. Methods To understand of the interaction between contextual factors and lighting variables, an experiment was conducted. 10 singles and 10 couples had to manipulate lighting variables such as intensity and colorin five everyday situations for pleasant lighting experience. Results The result of the experiment showed that illuminance, color temperature and hue are influenced by the degree of concentration, but only partially influenced by social factors. The findings could provide a better understanding of manipulating lighting variables in terms of use context with design practitioners. Conclusions The overall findings of the study indicate that illuminance, color temperature, and hue are significantly dependent upon the level of concentration required in at-home lighting use, and also have only a partial dependence on social effect. This implies that although we assumed that people have their personal lighting preferences, their preferences can be largely dependent on the degree of concentration required for at-home pleasant lighting use. Hence, there are common patterns among people in manipulating lighting parameters, which are less dependent on personal differences. © Archives of Design Researc

The Effects of Transcranial Direct Current Stimulation on the Cognitive and Behavioral Changes After Electrode Implantation Surgery in Rats

Postoperative delirium can lead to increased morbidity and mortality, and may even be a potentially life-threatening clinical syndrome. However, the neural mechanism underlying this condition has not been fully understood and there is little knowledge regarding potential preventive strategies. To date, investigation of transcranial direct current stimulation (tDCS) for the relief of symptoms caused by neuropsychiatric disorders and the enhancement of cognitive performance has led to promising results. In this study, we demonstrated that tDCS has a possible effect on the fast recovery from delirium in rats after microelectrode implant surgery, as demonstrated by postoperative behavior and neurophysiology compared with sham stimulation. This is the first study to describe the possible effects of tDCS for the fast recovery from delirium based on the study of both electroencephalography and behavioral changes. Postoperative rats showed decreased attention, which is the core symptom of delirium. However, anodal tDCS over the right frontal area immediately after surgery exhibited positive effects on acute attentional deficit. It was found that relative power of theta was lower in the tDCS group than in the sham group after surgery, suggesting that the decrease might be the underlying reason for the positive effects of tDCS. Connectivity analysis revealed that tDCS could modulate effective connectivity and synchronization of brain activity among different brain areas, including the frontal cortex, parietal cortex, and thalamus. It was concluded that anodal tDCS on the right frontal regions may have the potential to help patients recover quickly from delirium

Latent Sensitization in a Mouse Model of Ocular Neuropathic Pain

Purpose: Chronic ocular pain is poorly understood and difficult to manage. We developed a murine model of corneal surface injury (CSI)–induced chronic ocular neuropathic pain. The study focuses on changes in corneal nerve morphology and associated short- and long-term pain-like behavior after CSI. Methods: CSI was induced in mice by local application of an alkali solution (0.75 N NaOH). Corneal nerve architecture, morphology, density, and length were studied. Eye-wiping was evaluated before and after CSI in response to hypertonic saline (2 M NaCl). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or topically (eye drop, 100 μM), and then an eye-wiping test was performed. Results: CSI caused partial corneal deinnervation followed by gradual reinnervation. Regenerated nerves displayed increased tortuosity, beading, and branching. CSI enhanced hypertonic saline-induced eye-wiping behavior compared to baseline or sham-injury (P \u3c 0.01). This hypersensitivity peaked at 10 days and subsided 14 days after CSI. Administration of NTX, or NLX-me, a selective peripheral opioid antagonist, reinstated eye-wiping behavior in the injury group, but not in the sham groups (P \u3c 0.05). Conclusions: This study introduces a model of chronic ocular pain and corneal neuropathy following CSI. CSI induces central and peripheral opioid receptor-dependent latent sensitization (LS) that is unmasked by systemic or topical administration of opioid antagonists. Translational Relevance: This model of chronic ocular pain establishes LS as a new inhibitory mechanism in the oculotrigeminal system and may be used for potential diagnostic and therapeutic interventions for ocular neuropathy

Neurotropic Lineage III Strains of \u3cem\u3eListeria monocytogenes\u3c/em\u3e Disseminate to the Brain without Reaching High Titer in the Blood

Listeria monocytogenes is thought to colonize the brain using one of three mechanisms: direct invasion of the blood-brain barrier, transportation across the barrier by infected monocytes, and axonal migration to the brain stem. The first two pathways seem to occur following unrestricted bacterial growth in the blood and thus have been linked to immunocompromise. In contrast, cell-to-cell spread within nerves is thought to be mediated by a particular subset of neurotropic L. monocytogenes strains. In this study, we used a mouse model of foodborne transmission to evaluate the neurotropism of several L. monocytogenes isolates. Two strains preferentially colonized the brain stems of BALB/cByJ mice 5 days postinfection and were not detectable in blood at that time point. In contrast, infection with other strains resulted in robust systemic infection of the viscera but no dissemination to the brain. Both neurotropic strains (L2010-2198, a human rhombencephalitis isolate, and UKVDL9, a sheep brain isolate) typed as phylogenetic lineage III, the least characterized group of L. monocytogenes. Neither of these strains encodes InlF, an internalin-like protein that was recently shown to promote invasion of the blood-brain barrier. Acute neurologic deficits were observed in mice infected with the neurotropic strains, and milder symptoms persisted for up to 16 days in some animals. These results demonstrate that neurotropic L. monocytogenes strains are not restricted to any one particular lineage and suggest that the foodborne mouse model of listeriosis can be used to investigate the pathogenic mechanisms that allow L. monocytogenes to invade the brain stem. IMPORTANCE Progress in understanding the two naturally occurring central nervous system (CNS) manifestations of listeriosis (meningitis/meningoencephalitis and rhombencephalitis) has been limited by the lack of small animal models that can readily distinguish between these distinct infections. We report here that certain neurotropic strains of Listeria monocytogenes can spread to the brains of young otherwise healthy mice and cause neurological deficits without causing a fatal bacteremia. The novel strains described here fall within phylogenetic lineage III, a small collection of L. monocytogenes isolates that have not been well characterized to date. The animal model reported here mimics many features of human rhombencephalitis and will be useful for studying the mechanisms that allow L. monocytogenes to disseminate to the brain stem following natural foodborne transmission

Association of smoking cessation after atrial fibrillation diagnosis on the risk of cardiovascular disease: a cohort study of South Korean men

While smoking elevates the risk for cardiovascular disease (CVD) among atrial fibrillation (AF) patients, whether smoking cessation after AF diagnosis actually leads to reduced CVD risk is unclear. We aimed to determine the association of smoking cessation after AF diagnosis with subsequent CVD Risk among South Korean men. This retrospective cohort study included 2372 newly diagnosed AF male patients during 2003–2012 from the Korean National Health Insurance Service database. Self-reported smoking status within 2 years before and after diagnosis date were determined, after which the participants were divided into continual smokers, quitters (smokers who quit after AF diagnosis), sustained-ex smokers (those who quit prior to AF diagnosis), and never smokers. Participants were followed up from 2 years after AF diagnosis until 31 December 2015 for CVD. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for CVD according to the change in smoking habits before and after AF diagnosis. The mean (standard deviation, minimum-maximum) age of the study subjects was 62.5 (8.6, 41–89) years. Among AF patients, quitters had 35% reduced risk (aHR 0.65, 95% CI 0.44–0.97) and never smokers had 32% reduced risk (aHR 0.68, 95% CI 0.52–0.90) for CVD compared to continual smokers (p for trend 0.020). Similarly, compared to continual smokers, quitters had 41% risk-reduction (aHR 0.59, 95% CI 0.35–0.99) and never smokers 34% risk-reduction (aHR 0.66, 95% CI 0.46–0.93) for total stroke (p for trend 0.047). Quitters had 50% reduction (aHR 0.50, 95% CI 0.27–0.94), sustained ex-smokers had 36% reduction (aHR 0.64, 95% CI 0.42–0.99), and never smokers had 39% reduction (aHR 0.61, 95% CI 0.41–0.91) in ischemic stroke risk (p for trend 0.047). The risk-reducing effect of quitting on CVD risk tended to be preserved regardless of aspirin or warfarin use. Smoking cessation after AF diagnosis was associated with reduced CVD, total stroke, and ischemic stroke risk