scholarly journals Cerebral Microvascular Damage Occurs Early after Hypoxia–Ischemia via nNOS Activation in the Neonatal Brain

2014 ◽  
Vol 34 (4) ◽  
pp. 668-676 ◽  
Author(s):  
Yi-Ching Hsu ◽  
Ying-Chao Chang ◽  
Yung-Chieh Lin ◽  
Chun-I Sze ◽  
Chao-Ching Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Damage ◽  
Cerebral Perfusion ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Nitric Oxide Synthases ◽  
Neonatal Brain ◽  
Microvascular Damage ◽  
Vascular Lumen

Microvascular injury early after hypoxic ischemia (HI) may contribute to neonatal brain damage. N-methyl-D-aspartate receptor overstimulation activates neuronal nitric oxide synthases (nNOS). We hypothesized that microvascular damage occurs early post-HI via nNOS activation and contributes to brain injury. Postpartum day-7 rat pups were treated with 7-nitroindazole (7-NI) or aminoguanidine (AG) before or after HI. Electron microscopy was performed to measure neuronal and endothelial cell damage. There were vascular lumen narrowing at 1 hour, pyknotic neurons at 3 hours, and extensive neuronal damage and loss of vessels at 24 hours post HI. Early after reoxygenation, there were neurons with heterochromatic chromatin and endothelial cells with enlarged nuclei occluding the lumen. There was also increased 3-nitrotyrosin in the microvessels and decreased cerebral blood perfusion. 7-NI and AG treatment before hypoxia provided complete and partial neuroprotection, respectively. Early post-reoxygenation, the AG group showed significantly increased microvascular nitrosative stress, microvascular interruptions, swollen nuclei that narrowed the vascular lumen, and decreased cerebral perfusion. The 7-NI group showed significantly decreased microvascular nitrosative stress, patent vascular lumen, and increased cerebral perfusion. Our results indicate that microvascular damage occurs early and progressively post HI. Neuronal nitric oxide synthases activation contributes to microvascular damage and decreased cerebral perfusion early after reoxygenation and worsens brain damage.

scholarly journals Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model

Critical Care ◽  
2010 ◽  
Vol 14 (4) ◽  
pp. R129 ◽  
Author(s):  
Matthias Lange ◽  
Rhykka Connelly ◽  
Daniel L Traber ◽  
Atsumori Hamahata ◽  
Yoshimitsu Nakano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Time Course ◽  
Nitrosative Stress ◽  
Nitric Oxide Synthases ◽  
Adp Ribosylation ◽  
Sepsis Model

scholarly journals Oxidative and nitrosative stress in brain mitochondria of diabetic rats

2005 ◽  
Vol 187 (1) ◽  
pp. 37-44 ◽  
Author(s):  
R Mastrocola ◽  
F Restivo ◽  
I Vercellinatto ◽  
O Danni ◽  
E Brignardello ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Manganese Superoxide Dismutase ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Brain Mitochondria ◽  
Brain Dysfunction ◽  
Diabetic Rats ◽  
Oxidative And Nitrosative Stress ◽  
Chronic Hyperglycemia ◽  
Mitochondrial Nitric Oxide Synthase

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.

scholarly journals Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1097
Author(s):  
Joanna M Wierońska ◽  
Paulina Cieślik ◽  
Leszek Kalinowski
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Reactive Astrocytes ◽  
Ischemic Hypoxia ◽  
Inflammatory Proteins ◽  
Brain Tissue Damage

Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO•), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive oxygen and nitrogen species (ROS/RNS) in neurons due to NO• synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1α (HIF-1α) and HIF-1α-dependent genes activated in reactive astrocytes play essential roles in this process. The review summarizes the roles of NO•-dependent pathways in the early and late aftermath of stroke and treatments based on the stimulation or inhibition of particular NO• synthases and the stabilization of HIF-1α activity.

scholarly journals NNC 26-9100 increases Aβ1-42 phagocytosis, inhibits nitric oxide production and decreases calcium in BV2 microglia cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254242
Author(s):  
Joseph Schober ◽  
Jahnavi Polina ◽  
Field Walters ◽  
Nathan Scott ◽  
Eric Lodholz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lactate Dehydrogenase ◽  
Nitrosative Stress ◽  
Immune Cell ◽  
Cell Damage ◽  
Cytosolic Calcium ◽  
Alamar Blue ◽  
Nitric Oxide Release ◽  
Bv2 Microglia ◽  
The Brain

Microglia are the resident immune cell of the brain involved in the development and progression of Alzheimer’s disease (AD). Modulation of microglia activity represents a potential mechanism for treating AD. Herein, the compound NNC 26–9100 (NNC) was evaluated in toxicity, nitric oxide release, Aβ1–42 uptake and cytosolic calcium assays during lipopolysaccharide (LPS)-activated conditions using mouse BV2 microglia cells. After 24 hours, LPS increased cell toxicity in the alamar blue and lactate dehydrogenase assays, increased nitrite release, and increase cytoplasmic calcium. Addition of NNC decreased the LPS-induce lactate dehydrogenase release, had no effect in the alamar blue assay, decreased nitrite release and decreased cytosolic calcium. In the absence of LPS, NNC increased uptake of FITC-tagged Aβ1–42. These data demonstrate that NNC treatment decreases nitrosative stress and microglia cell damage during LPS-induced activation and enhances phagocytosis of Aβ1–42 during non-inflammatory conditions. Thus, NNC 26–9100 may have beneficial effects in AD and in inflammatory diseases of the brain through enhancement of microglial Aβ clearance, and cell protective effects through prevention of elevated cytosolic calcium and inhibition of nitric oxide release.

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