Nitric oxide in astrocyte-neuron signaling

Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca 2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+ -dependent mechanism, thus modulating neuronal activity and synaptic transmission.;In this dissertation, I investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First I tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, I applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockade of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, I tested the role of NO in glutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC). Although NO is not required for the SIC, PTIO reduced SIC amplitude, suggesting that NO modulates glutamate release from astrocytes or glutamate receptor sensitivity of neurons.;Taken together, these results demonstrate that NO is actively involved in astrocyte-neuron signaling. NO has been implicated in many nervous system functions including synaptic plasticity and neurotoxicity, but its exact role and functioning mechanisms are still unclear. By investigating the roles of NO in astrocyte-neuron signaling, this study could provide new insights into development, modulation and pathology of the nervous system

Nitric oxide in astrocyte-neuron signaling

Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca2+ elevations in response to neurotransmitters. A Ca 2+ elevation can propagate to adjacent astrocytes as a Ca2+ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca2+ -dependent mechanism, thus modulating neuronal activity and synaptic transmission.;In this dissertation, I investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First I tested if NO is generated during astrocytic Ca2+ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca2+-dependent NO production. To test the roles of NO in astrocytic Ca2+ signaling, I applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca2+, possibly through store-operated Ca2+ channels. The NO-induced Ca2+ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca2+ change. The consequence of this NO-induced Ca2+ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca2+ using fluorescent Ca2+ indicators x-rhod-1 and mag-fluo-4. Blockade of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca2+ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca2+ elevation in the stimulated astrocyte and a subsequent Ca2+ wave to neighbors. Finally, I tested the role of NO in glutamate-mediated astrocyte-neuron signaling by recording the astrocyte-evoked glutamate-dependent neuronal slow inward current (SIC). Although NO is not required for the SIC, PTIO reduced SIC amplitude, suggesting that NO modulates glutamate release from astrocytes or glutamate receptor sensitivity of neurons.;Taken together, these results demonstrate that NO is actively involved in astrocyte-neuron signaling. NO has been implicated in many nervous system functions including synaptic plasticity and neurotoxicity, but its exact role and functioning mechanisms are still unclear. By investigating the roles of NO in astrocyte-neuron signaling, this study could provide new insights into development, modulation and pathology of the nervous system.</p

Evaluation of Implementation and Effectiveness of China’s Antibiotic Stewardship in the First Affiliated Hospital of Sun Yat-sen University

Antibiotic stewardship has been prioritized by governments and health care organizations in recent years as antibiotic resistance is markedly increasing. A tertiary hospital in Guangzhou, China was chosen as a study example to undertake an implementation and effectiveness evaluation of China’s antibiotic stewardship to improve and promote antimicrobial stewardship nationwide. The general surgery department of the study hospital was utilized to examine surgical site infection, and samples from across the hospital were used to identify bloodstream infection. Data was analyzed using descriptive analysis, the Mann–Kendall trend test, logit model and panel data model, and t-tests. In terms of prophylactic and therapeutic antibiotic rational use, respectively, we evaluated implementation conditions, the correlation between implementation and corresponding disease progress, and the cost-effectiveness of China’s antibiotic stewardship. For perioperative prophylactic antibiotic use, antibiotic stewardship was found to have been well-implemented, cost-effective, and reduced the incidence of surgical site infection. However, concerning therapeutic use and antibiotic-resistant bacterial infection prophylaxis, the complexity of influencing factors and the contradiction between stewardship implementation and clinical demand needs to be further evaluated