scholarly journals Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening

2013 ◽  
Vol 115 (10) ◽  
pp. 1481-1486 ◽  
Author(s):  
Ming Yang ◽  
Paul Kosterin ◽  
Brian M. Salzberg ◽  
Tatyana N. Milovanova ◽  
Veena M. Bhopale ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Action Potential ◽  
Central Nervous System Injury ◽  
Neurological Injury ◽  
Circulating Microparticles ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Decompression Stress ◽  
Nadph Oxidase Activation

The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent polyethylene glycol telomere B immediately after decompression, were rendered thrombocytopenic, or were treated with an inhibitor of nitric oxide synthase-2 (iNOS) prior to decompression, or in knockout (KO) mice lacking myeloperoxidase or iNOS. If MPs were harvested from control (no decompression) mice and injected into naive mice, no AP broadening occurred, but AP broadening was observed with injections of equal numbers of MPs from either wild-type or iNOS KO mice subjected to decompression stress. Although not required for AP broadening, MPs from decompressed mice, but not control mice, exhibit NADPH oxidase activation. We conclude that inherent differences in MPs from decompressed mice, rather than elevated MPs numbers, mediate neurological injury and that a component of the perivascular response to MPs involves iNOS. Additional study is needed to determine the mechanism of AP broadening and also mechanisms for MP generation associated with exposure to elevated gas pressure.

Abstract 103: ACE2 Overexpression Prevents DOCA-Salt Hypertension by Modulating Oxidative Stress and Nitric Oxide in the Central Nervous System

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Srinivas Sriramula ◽  
Huijing Xia ◽  
Eric Lazartigues
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Nadph Oxidase ◽  
Salt Treatment ◽  
Salt Hypertension ◽  
The Central Nervous System ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Elevated reactive oxygen species (ROS) in the central nervous system (CNS) through NADPH oxidase and diminished Nitric oxide (NO) levels are involved in the pathogenesis of hypertension. We previously reported that central Angiotensin Converting Enzyme 2 (ACE2) overexpression prevents the development of hypertension induced by DOCA-salt in a transgenic mouse model (syn-hACE2; SA) with human ACE2 targeted selectively to neurons in the CNS. While baseline blood pressure (BP; telemetry) was not different among genotypes, DOCA-salt treatment (1mg/g body wt DOCA, 1% saline in drinking water for 3 weeks) resulted in significantly lower BP level in SA mice (122 ±3 mmHg, n=12) compared to non-transgenic (NT) littermates (138 ±3 mmHg, n=8). To elucidate the mechanisms involved in this response, we investigated the paraventricular nucleus (PVN) expression of Nox-2 (catalytic subunit of NADPH oxidase), 3-nitrotyrosine, and endothelial nitric oxide synthase (eNOS) and anti-oxidant enzymes superoxide dismutase (SOD) and catalase in the hypothalamus. DOCA-salt treatment resulted in decreased catalase (95.2 ±5.6 vs. 113.8 ±17.6 mmol/min/ml, p<0.05) and SOD (4.1 ±0.4 vs. 5.9 ±0.2 U/ml, p<0.01) activities in hypothalamic homogenates of NT mice, which was prevented by ACE2 overexpression (141.8 ±9.9 vs. 142.1 ±9.2 mmol/min/ml and 5.9 ±0.3 vs. 7.9 ±0.2 U/ml, respectively). NT mice treated with DOCA-salt showed increased oxidative stress as indicated by increased expression of Nox-2 (61 ±5 % increase, n=9, p<0.001 vs. NT) and 3-nitrotyrosine (89 ±32 % increase, n=9, p<0.01 vs. NT) in the PVN which was attenuated in SA mice. Furthermore, DOCA-salt hypertension resulted in decreased phosphorylation of eNOS-ser1177 in the PVN (33 ±5 % decrease, n=9, p<0.05 vs NT) and this decrease was prevented by ACE2 overexpression. Taken together, these data provide evidence that brain ACE2 regulates the balance between NO and ROS levels, thereby preventing the development of DOCA-salt hypertension.

scholarly journals PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41098-41104 ◽  
Author(s):  
Ruirui Yang ◽  
Caixia Xu ◽  
Tao Wang ◽  
Yuanqi Wang ◽  
Jingnan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Neural Stem Cells ◽  
Biological Properties ◽  
Central Nervous System Injury ◽  
Bioactive Molecules

The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells.

scholarly journals Progenitor Cell Therapy for the Treatment of Central Nervous System Injury: A Review of the State of Current Clinical Trials

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Peter A. Walker ◽  
Matthew T. Harting ◽  
Shinil K. Shah ◽  
Mary-Clare Day ◽  
Ramy El Khoury ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Neurological Injury ◽  
Cell Therapies ◽  
Potential Efficacy ◽  
Cord Injury

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system (CNS) injuries has shown potential neuroprotection in the setting of traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. Mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the locoregional inflammatory milieu, and modulation of the systemic immunologic/inflammatory response. While the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this paper, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of TBI, SCI, and ischemic stroke. Our review of the literature shows that while the preliminary clinical trials reviewed in this paper offer novel data supporting the potential efficacy of stem/progenitor cell therapies for CNS injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials.

scholarly journals QT Dispersion: A Predictor of Outcome Following Acute Neurologic Events

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 343-343
Author(s):  
Elzbieta J Wirkowski ◽  
Joseph Moonjely ◽  
Todd J Cohen ◽  
Stephanie M Manzella ◽  
Richard H Smith ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Functional Outcome ◽  
Qt Dispersion ◽  
Neurological Injury ◽  
Disease States ◽  
Qt Intervals ◽  
The Central Nervous System ◽  
The Difference ◽  
Adjusted Logistic Regression

P26 BACKGROUND: QT dispersion (QTD) reflects heterogeneity of myocardial repolarization, which is modulated by the central nervous system. Pervious studies have shown increased QTD to be a predictor of adverse outcome in various cardiac disease states. However, the central nervous system effects on QTD and its relation to functional outcomes have not been previously studied in patients with acute neurological events (NE). The objective of this study was to determine whether increased QTD is related to functional outcome in patients with cerebrovascular accidents (CVA) and transient ischemic attacks (TIA). METHODS: We studied 140 consecutive pts. aged 72±10 yrs. (48% male) admitted to our institution with NE from 1/98 to 4/98. QTD was calculated from admission EKG as the difference between maximum and minimum QT intervals. 120 pts. had interpretable EKGs with measurable QT intervals in at least 11 of 12 leads. Three separate functional scales (NIHSS, Barthel, and Rankin) were obtained on admission and discharge were recorded. RESULTS: QTD was higher in pts. with intracerebral hemorrhage as compared to CVA and TIA (70±15 vs. 53±27 vs. 48±31 msecs. p=0.03). Increased QTD was associated with lower functional outcome on all 3 scales (all p<0.05) and with higher mortality (p=0.02). QTD was higher in pts. with congestive heart failure (80±43 vs. 47±24 msecs. p=0.006) and carotid disease (59±32 vs. 46±27 msecs. p=0.045) as compared to those without. QTD was not associated with atrial fibrillation or coronary disease. All patients with TIA survived. On multivariate analysis, other independent predictors of poorer outcome were QTD (OR 1.35, 95% CI 1.08–1.68) and a trend towards age (OR 1.07, 95% CI 0.99–1.16). On age-adjusted logistic regression, mortality increased by an OR 1.28, 95% (CI 1.02–1.61) for every 10 msec increase in QTD. CONCLUSION: QTD is an independent predictor of functional outcome and mortality following acute neurological events. In this setting, QTD reflects acute neurological injury as well as underlying heart disease. The mechanism of these findings merits further study.

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