scholarly journals Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 640-640
Author(s):  
Krista Lamorie-Foote ◽  
Kristina Shkirkova ◽  
Qinghai Liu ◽  
Constantinos Sioutas ◽  
Todd Morgan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Corpus Callosum ◽  
Diesel Exhaust ◽  
Time Course ◽  
Ambient Air ◽  
White Matter Injury ◽  
Ambient Air Pollution ◽  
Diesel Exhaust Particulate ◽  
And Oxidative Stress

Abstract Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.001), 100 (p=0.001), and 200 hours (p<0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.

Acute brain inflammation, white matter oxidative stress, and myelin deficiency in a model of neonatal intraventricular hemorrhage

2020 ◽  
Vol 26 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Danielle S. Goulding ◽  
R. Caleb Vogel ◽  
John C. Gensel ◽  
Josh M. Morganti ◽  
Arnold J. Stromberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
White Matter ◽  
Rat Model ◽  
Intraventricular Hemorrhage ◽  
Time Course ◽  
Brain Inflammation ◽  
Current Therapy ◽  
Posthemorrhagic Hydrocephalus ◽  
And Oxidative Stress

OBJECTIVENeonatal intraventricular hemorrhage (IVH) leads to posthemorrhagic hydrocephalus (PHH), brain injury, and long-term disability. Current therapy for IVH is based on treating PHH but does not address the underlying brain injury. In order to develop pharmacological treatment for IVH, there must be a better understanding of the underlying pathology of this disease. This study was designed to determine the time course of the acute inflammation and oxidative stress that may underlie the progressive pathology of IVH. The authors sought to understand the temporal relationships among inflammation, oxidative stress, and white matter pathology in a rat model of IVH.METHODSA rat model of IVH consisting of hemoglobin injection into the lateral ventricle was used. Tissue was analyzed via biochemical and histological methods to map the spatiotemporal distribution of innate immune activation and oxidative stress. White matter was quantified using both immunohistochemistry and Western blot for myelin basic protein (MBP) in the corpus callosum.RESULTSIVH led to acute induction of inflammatory cytokines, followed by oxidative stress. Oxidative stress was concentrated in white matter, adjacent to the lateral ventricles. Animals with IVH initially gained weight at a lower rate than control animals and had larger ventricles and less MBP than control animals.CONCLUSIONSExperimental IVH induces global inflammation throughout the brain and oxidative stress concentrated in the white matter. Both of these phenomena occur early after IVH. This has implications for human neonates with immature white matter that is exquisitely sensitive to inflammation and oxidative stress. Antiinflammatory or antioxidant therapy for IVH may need to be initiated early in order to protect developing white matter.

scholarly journals Ambient Air Pollution Increases the Risk of Cerebrovascular and Neuropsychiatric Disorders through Induction of Inflammation and Oxidative Stress

2020 ◽  
Vol 21 (12) ◽  
pp. 4306 ◽  
Author(s):  
Omar Hahad ◽  
Jos Lelieveld ◽  
Frank Birklein ◽  
Klaus Lieb ◽  
Andreas Daiber ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Air Pollution ◽  
Air Pollutants ◽  
Molecular Mechanisms ◽  
Ambient Air ◽  
Neuropsychiatric Disorders ◽  
Ambient Air Pollution ◽  
Enhanced Production ◽  
Increased Risk ◽  
And Oxidative Stress

Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson’s disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.

Abstract 36: Nanoparticulate Matter Exposure Causes a Time-Dependent Activation of Inflammatory Microglia With Associated White Matter Damage in a Mouse Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michelle Connor ◽  
Hans Baertsch ◽  
Kristina Shkirkova ◽  
Ashley Knebel ◽  
Krista Lamorie-Foote ◽  
...  
Keyword(s):  
Air Pollution ◽  
White Matter ◽  
Corpus Callosum ◽  
Immunohistochemical Staining ◽  
Inflammatory Cells ◽  
Ambient Air ◽  
Microglia Activation ◽  
Ambient Air Pollution ◽  
White Matter Damage ◽  
Myelin Injury

Introduction: Exposure to ambient air pollution, specifically the nano-scale subfraction (nPM; particles <200nm diameter), is associated with white matter damage and neurocognitive decline in both experimental and human studies. The histopathology and cognitive correlates are similar to those observed in vascular dementia and small vessel ischemic disease. nPM-associated white matter damage involves microglial activation. However, the microglial phenotype and time course of white matter damage remain uncharacterized. This study examines myelin injury and microglia activation in the corpus callosum of mice exposed to 3 weeks (45 hours) and 10 weeks (150 hours) of nPM. Methods: Air pollution consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles; nPM was isolated and stored. Mice were exposed to either re-aerosolized nPM or filtered air for 3 weeks (45 hours) or 10 weeks (150 hours) (n=18/group). Activated microglia were characterized by immunohistochemical staining of Iba-1+iNOS to identify M1 pro-inflammatory cells, and Iba-1+Arg to identify M2 anti-inflammatory cells. Myelin injury was assessed by immunohistochemical staining of myelin associated glycoprotein (MAG), a marker of normal myelin; and degraded myelin basic protein (dMBP), specific for myelin degradation. Results: M1 pro-inflammatory microglia were significantly increased in the corpus callosum of mice exposed 10 weeks of nPM compared to filtered air (p<0.05). This was accompanied by a significant decrease in MAG (p<0.05), and increase in dMBP (p<0.05) immunofluorescent density. Mice exposed to 3 weeks of nPM did not demonstrate any differences in microglia activation or white matter injury, compared to mice exposed to filtered air (p=NS). Conclusion: 10 week, but not 3 week, exposure to nPM results in inflammatory microglia activation and myelin injury in the corpus callosum of mice. M1 pro-inflammatory microglia release inflammatory cytokines and reactive oxygen/ nitrogen species, which may contribute to the white matter damage observed in this model.

Time course of skeletal muscle loss and oxidative stress in rats with walker 256 solid tumor

2010 ◽  
Vol 42 (6) ◽  
pp. 950-958 ◽  
Author(s):  
Flávia A. Guarnier ◽  
Alessandra L. Cecchini ◽  
Andréia A. Suzukawa ◽  
Ana Leticia G.C. Maragno ◽  
Andréa N.C. Simão ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Solid Tumor ◽  
Time Course ◽  
Muscle Loss ◽  
Skeletal Muscle Loss ◽  
Walker 256 ◽  
And Oxidative Stress

Cd(2+)-induced injury in CNS white matter

1996 ◽  
Vol 76 (5) ◽  
pp. 3264-3273 ◽  
Author(s):  
R. Fern ◽  
J. A. Black ◽  
B. R. Ransom ◽  
S. G. Waxman
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Mitochondrial Respiration ◽  
Time Course ◽  
White Matter Injury ◽  
Neurological Injury ◽  
Antimycin A ◽  
Optic Nerves ◽  
Voltage Gated ◽  
Ca2 Channels

1. The affect of extracellular Cd2+ on CNS white matter was studied using an isolated rat optic nerve preparation. A 100-min exposure to 200 microM Cd2+ reduced the area of the compound action potential (CAP) recorded from the optic nerve to 32.6 +/- 3.8% (mean +/- SE) of the preexposure area, compared with a reduction to 74.9 +/- 2.9% after 100 min in control conditions (P > 0.001). This CAP reduction was not reversed after 120 min of reperfusion with Cd(2+)-free solution, or by perfusion with Cd2+ chelators. 2. Cd(2+)-induced CAP loss occurred in the absence of extracellular Ca2+. Increasing extracellular Ca2+ concentration to 16 mM, however, prevented Cd(2+)-induced CAP loss. Once evident, Cd(2+)-induced CAP reduction could not subsequently be reversed by addition of 16 mM Ca2+. 3. Low concentrations of Cd2+ (60 microM) did not significantly reduce CAP area. This concentration of Cd2+ combined with high extracellular K+ (30 mM) caused CAP loss that was blocked by 10 microM nifedipine, an antagonist of L-type voltage-gated Ca2+ channels. 4. Treatment with pharmacological inhibitors of membrane proteins known to be inhibited by Cd2+ did not affect the CAP. These included inhibitors of voltage-gated Ca2+ channels, Ca(2+)-activated K+ channels, Ca(2+)-ATPase and the Na+/Ca2+ exchanger. 5. Treatment with pharmacological agents that inhibit calmodulin or disrupt tubulin, two intracellular proteins affected by Cd2+, did not affect CAP area. 6. The effect of Cd2+ was not prevented by pretreatment with (+)-cyanidanol-3, an agent that prevents Cd(2+)-induced lipid peroxidation. 7. Treatment with antimycin A, a inhibitor of mitochondrial respiration, resulted in irreversible CAP reduction with a time course and extent similar to that produced by 200 microM Cd2+. Cd(2+)-induced CAP reduction was prevented by 1 mM cysteine, which prevents Cd(2+)-induced disruption of mitochondrial respiration. 8. The ultrastructure of optic nerves exposed to 200 microM Cd2+ for 100 min was characterized by swollen mitochondria with disrupted cristae and dissolution of microtubules, which were replaced by flocculent debris. Occasional regions of axonal swelling and empty spaces beneath the myelin also were found. Qualitatively similar changes in mitochondria and cytoskeletal elements were found in optic nerves exposed to antimycin A for 100 min. Astrocytes also displayed disrupted mitochondria and had an electron-lucent appearance under both conditions. 9. The neurological injury produced by exposure to Cd2+ is characterized by lesions of CNS white matter. Our results indicate that Cd(2+)-induced white matter injury in vitro results largely from disruption of mitochondrial respiration after Cd2+ influx through routes that include voltage-gated Ca2+ channels.

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