Abstract WP112: Residual Damage is Reduced Following Human Umbilical Tissue Derived Cell Infusion in a Non-human Primate Model of Cortical Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mary E Orczykowski ◽  
Eli Shobin ◽  
Samantha M Calderazzo ◽  
Brian C Kramer ◽  
Farzad Mortazavi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Motor Cortex ◽  
Oxidative Damage ◽  
Primary Motor Cortex ◽  
Primate Model ◽  
Cortical Injury ◽  
Activated Microglia ◽  
And Oxidative Stress ◽  
Human Primate

Introduction: Stroke is the leading cause of long-term disability in the United States due to impairments that endure after brain injury. While studies in rodent models have evaluated numerous neurorestorative treatments following stroke, none have received FDA approval. We evaluated a therapy using human umbilical tissue-derived cells (hUTC) as a potential neurorestorative treatment in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Given treatment 24 hours after injury, hUTC treated monkeys showed a significantly greater degree of recovery of fine motor function compared to vehicle treated controls (Moore et al., 2013). To explore the effect of hUTC, histopathological markers of inflammation and oxidative stress were assessed. Hypothesis: Treatment with hUTC will enhance the recruitment of glia to the injury and reduce the cascade of inflammation and oxidative stress. Methods: Using immunohistochemistry, activated microglia (LN3), reactive astrocytes (GFAP), oxidative damage (4HNE), and accumulated hemosiderin (Perls’ Prussian Blue) were quantified in ipsilesional primary motor cortex and underlying white matter. Microglia were counted using unbiased stereology. A Sholl Analysis was performed on traced perilesional astrocytes. The area of oxidative damage and hemosiderin was assessed using densitometry. Results: Compared to vehicle controls, density of activated microglia in the hUTC treated group approached a significant increase in the perilesional gray and white matter (p=0.070; p=0.092). Astrocytes exhibited more complex processes in treated monkeys (p=0.042). Staining for 4HNE was significantly reduced in white matter underlying the lesion in treated monkeys (p=0.033). Lastly, both the area and intensity of Perls’ staining for hemosiderin was significantly reduced in the perilesional area of treated monkeys (p=0.045; p=0.001). Conclusions: Treatment with hUTC resulted in increased activation of microglia and complexity of reactive astrocyte processes as well as reduced post-lesion oxidative damage and hemosiderin deposition. This suggests the hUTC treatment enhanced recovery, in part, by recruitment of glial cells that limited the damage following cortical injury.

The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs

2018 ◽  
Vol 40 (5-6) ◽  
pp. 497-507 ◽  
Author(s):  
Vanesa Stojanovska ◽  
Samantha K. Barton ◽  
Mary Tolcos ◽  
Andrew W. Gill ◽  
Martin Kluckow ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
White Matter ◽  
Oxygen Delivery ◽  
Late Preterm ◽  
Limited Information ◽  
Fetal Sheep ◽  
Activated Microglia ◽  
Protein Extravasation ◽  
To Receive ◽  
And Oxidative Stress

Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVCSal, n = 4; UVCBM, n = 6) were humanely killed without intervention; ventilated lambs (VentSal, n = 5; VentBM, n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVCBM than in UVCSal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in ­VentBM lambs (p < 0.05 vs. VentSal). In the subcortical WM, microglial infiltration was increased in the VentSal group compared to UVCSal. The proportion of activated microglia and protein extravasation was higher in the VentBM group compared to VentSal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the VentBM group compared to UVCSal, UVCBM, and VentSal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

scholarly journals Enhanced Synchrony among Primary Motor Cortex Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinson's Disease

2002 ◽  
Vol 22 (11) ◽  
pp. 4639-4653 ◽  
Author(s):  
Joshua A. Goldberg ◽  
Thomas Boraud ◽  
Sharon Maraton ◽  
Suzanne N. Haber ◽  
Eilon Vaadia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Primate Model

Abstract TP441: Neurovascular Coupling is Impaired in Cerebral Amyloid Angiopathy

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Stefano Peca ◽  
Cheryl R McCreary ◽  
Emily Donaldson ◽  
Karla Sanchez ◽  
Anna Charlton ◽  
...  
Keyword(s):  
White Matter ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
White Matter Lesion ◽  
Motor Task ◽  
Neurovascular Coupling ◽  
Occipital Lobe ◽  
Amyloid Angiopathy ◽  
Bold Response ◽  
Cerebral Amyloid

Introduction: Cerebral amyloid angiopathy (CAA) is marked by accumulation of vascular beta-amyloid which is toxic to smooth muscle cells. An animal study and a pilot study in humans suggest decreased vasodilation in CAA. We studied patients with CAA and matched controls to determine whether neurovascular coupling is impaired in CAA. Methods: Patients with CAA and controls underwent task-related fMRI with a visual task (viewing a flashing alternating checkerboard pattern) or a motor task (tapping the fingers of the dominant hand) using a block design, and visual evoked potentials (VEPs). CAA patients were diagnosed by Boston criteria and had normal corrected visual acuity, no visual field deficits and no paresis of the dominant arm. Controls were recruited by community advertising and were matched by gender and age (±5 years) to CAA cases. Results: Eighteen CAA patients (12 M, 6F; 72±7 yrs) and eighteen controls (12 M, 6F; 70±7 yrs) were studied. For the visual task, CAA patients had reduced activity in the occipital lobe (Figure) and lower amplitude of the BOLD response vs. controls (28% reduced, p=0.005). By contrast, for the motor task CAA patients had a similar response of the primary motor cortex vs. controls (9.6% reduced BOLD response, p=0.53). VEP P100 latencies and amplitudes did not differ between CAA and controls (p=0.49 and p=0.74). Lower visual cortex BOLD amplitudes were correlated with greater white matter lesion volumes in CAA (r=-0.66, p=0.003). Conclusions: Neurovascular coupling is impaired in the occipital lobe in CAA. BOLD signal amplitudes are reduced despite normal evoked potentials, suggesting impaired vasodilation. The association with white matter lesion volume raises the possibility that impaired vasodilation may be involved in the pathogenesis of these lesions. BOLD responses in the primary motor cortex in CAA were not reduced, likely reflecting the known posterior predominance of CAA with lesser involvement of the frontal lobe.

scholarly journals Protective effects of a cocktail of lactic acid bacteria on microcystin-LR-induced hepatotoxicity and oxidative damage in BALB/c mice

RSC Advances ◽  
2017 ◽  
Vol 7 (33) ◽  
pp. 20480-20487 ◽  
Author(s):  
Jichun Zhao ◽  
Fengwei Tian ◽  
Qixiao Zhai ◽  
Ruipeng Yu ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Oxidative Damage ◽  
Protective Effects ◽  
And Oxidative Stress

The aim of this study was to investigate the effects of mixed lactic acid bacteria (LAB) against microcystin-LR-exposed hepatotoxicity and oxidative stress in BALB/c mice.

scholarly journals Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 177 ◽  
Author(s):  
Anna Picca ◽  
Giuseppe Sirago ◽  
Vito Pesce ◽  
Angela Maria Serena Lezza ◽  
Riccardo Calvani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Transcription Factor ◽  
Oxidative Damage ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Transcription ◽  
Mitochondrial Mass ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A ◽  
And Oxidative Stress

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

scholarly journals Self-Reported Exposure to ETS (Environmental Tobacco Smoke), Urinary Cotinine, and Oxidative Stress Parameters in Pregnant Women—The Pilot Study

2019 ◽  
Vol 16 (9) ◽  
pp. 1656 ◽  
Author(s):  
Lubica Argalasova ◽  
Ingrid Zitnanova ◽  
Diana Vondrova ◽  
Monika Dvorakova ◽  
Lucia Laubertova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Antioxidant Capacity ◽  
Pregnant Women ◽  
Environmental Tobacco Smoke ◽  
Tobacco Smoke ◽  
Passive Smoking ◽  
Oxidative Stress Parameters ◽  
And Oxidative Stress ◽  
Stress Parameters

Background: Exposure to ETS (environmental tobacco smoke) is one of the most toxic environmental exposures. Objective: To investigate the association of ETS with physiological, biochemical, and psychological indicators, as well as with urine antioxidant capacity (AC) and oxidative damage to lipids in a pilot sample of healthy pregnant women. Methods: Exposure to ETS was investigated via a validated questionnaire, and urine cotinine and the marker of oxidative damage to lipids via 8-isoprostane concentrations using an ELISA kit. Urine AC was determined by the spectrophotometric Trolox-equivalent antioxidant capacity (TEAC) method. From a sample of pregnant women (n = 319, average age 30.84 ± 5.09 years) in 80, the levels of cotinine and oxidative stress markers were analyzed. Results: Among the 80 pregnant women, 5% (7.4% confirmed by cotinine) reported being current smokers and 25% reported passive smoking in the household (18.8% confirmed by cotinine). The Kappa was 0.78 for smokers and 0.22 for ETS-exposed nonsmokers. Pregnant women in the ETS-exposed group had significantly reduced AC compared to both the nonsmoker (ETS−) and the smoker groups (p < 0.05). Nonsmokers had significantly lower levels of 8-isoprostane than smokers (p < 0.01) and ETS-exposed nonsmokers (p < 0.05). Correlations between urine levels of cotinine and AC were positive in ETS-exposed nonsmokers. Conclusion: A harmful association of active and passive smoking and oxidative stress parameters among pregnant women has been indicated.

Quercetin protects rat hepatocytes from oxidative damage induced by ethanol and iron by maintaining intercellular liable iron pool

2013 ◽  
Vol 33 (5) ◽  
pp. 534-541 ◽  
Author(s):  
Y Li ◽  
Y Deng ◽  
Y Tang ◽  
H Yu ◽  
C Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Iron Overload ◽  
Combined Treatment ◽  
Rat Hepatocytes ◽  
Redox Status ◽  
Glutathione Depletion ◽  
Labile Iron Pool ◽  
Iron Pool ◽  
And Oxidative Stress

Accumulating evidence has shown that ethanol-induced iron overload plays a crucial role in the development and progression of alcoholic liver disease. We designed the present study to investigate the potential protective effect of quercetin, a naturally occurring iron-chelating antioxidant on alcoholic iron overload and oxidative stress. Ethanol-incubated (100 mmol/L) rat primary hepatocytes were co-treated by quercetin (100 µmol/L) and different dose of ferric nitrilotriacetate (Fe-NTA) for 24 h. When the hepatic enzyme releases in the culture medium, redox status of hepatocytes and the intercellular labile iron pool (LIP) level were assayed. Our data showed that Fe-NTA dose dependently induced cellular leakage of aspartate transaminase and lactate dehydrogenase, glutathione depletion, superoxide dismutase inactivation, and overproduction of malondialdehyde) and reactive oxygen species (ROS) of intact and especially ethanol-incubated hepatocytes. The oxidative damage resulted from ethanol, Fe-NTA, and especially their combined treatment was substantially alleviated by quercetin, accompanying the corresponding normalization of intercellular LIP level. Iron in excess, thus, may aggravate ethanol hepatotoxicity through Fenton-active LIP, and quercetin attenuated ethanol-induced iron and oxidative stress. To maintain intercellular LIP contributes to the hepatoprotective effect of quercetin besides its direct ROS-quenching activity.

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