bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bromine Exposure In Pregnant Mice May Reduce VEGF Signaling Via Increased Circulating VEGF Decoy Receptor sFlt‐1
Authors: Lambert James , Aggarwal Saurabh , Ford David , Patel Rakesh , Jilling Tamas , Matalon Sadis 
Published: June 2021

Inhalation of oxidant gas and vapor like the halogen bromine (Br2) may pose an increased threat to pregnant women and their unborn fetuses. We recently published that pregnant (P) C57Bl/6 mice exposed to 600 ppm Br2 for 30 minutes on gestational day 14.5 (E14.5) exhibited increased mortality, lung injury, and blood pressure at E18.5 when compared to similarly exposed non‐pregnant (NP) mice. Additionally, fetuses of Br2‐exposed pregnant mice displayed severe growth restriction, which cumulatively indicated a preeclampsia‐like phenotype. Administration of the phosphodiesterase 5 (PDE5) inhibitor tadalafil abrogated or significantly mitigated these effects in Br2‐exposed pregnant mice but had no effect on non‐pregnant counterparts. We hypothesize that exposure to Br2 via inhalation in pregnant mice results in placental damage and subsequent release of anti‐angiogenic molecules into maternal circulation resulting in systemic endothelial dysfunction and a vasoconstrictive environment mediated by dysfunctional VEGF signaling. Firstly, we have identified significant increases at 0.5 h post‐Br2 exposure of circulating brominated fatty acids and fatty acid aldehydes (2‐BrPA and 2‐BrPALD) as well as their glutathionylated species at 6h. These may serve as potential biomarkers and/or mediators of Br2‐inhalation induced systemic injury. Furthermore, preliminary results indicate aortas incubated ex vivo in the presence of 2‐BrPA and 2‐BrPALD are more sensitive to the vasoconstricting agent phenylephrine and less sensitive to the vasodilator acetylcholine. Similarly, aortas pregnant mice exposed to Br2 are less sensitive to acetylcholine when compared with similarly exposed non‐pregnant mice. Secondly, utilizing time‐course measurements, we have identified increases in the circulating VEGF decoy receptor sFlt‐1 beginning at 72h post‐exposure in pregnant mice. No increase is observed in similarly exposed non‐pregnant mice (PBr272h 7280.3 ± 1592 vs NPBr272h 1233.5 ± 1063 pg/mL p≤0.001). Additionally, this time point also coincides with a pregnancy specific increase in lung edema/injury as evidenced by lung wet:dry weight ratios (P Br272h 4.68 ± 0.10 vs NP Br272h 4.22 ± 0.04 p≤0.05). Lastly, supplementation of exogenous VEGF‐121 intended to overcome the effects of increased circulating sFlt‐1 improves both survival and weight gain profiles of pregnant mice exposed to Br2 as well as their fetuses. This study implicates diminished VEGF signaling in pregnancy specific Br2 inhalation injury contributing to increased blood pressures, lung injury and subsequent mortality.Support or Funding InformationNIEHS CounterACT ‐5U01ES026458 02, 1 U01 ES027697 01, Ruth L. Kirschstein National Research Service Award Institutional Training Grant ‐ T32HL007918.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sleep Deprivation and Sympathetic Neural Control in Older Adults
Authors: Fonkoue Ida T. , Greenlund Ian M. , Schwartz Christopher E. , Smoot Carl A. , Mokhlesi Babak , Carter Jason R. 
Published: June 2021

Epidemiological studies have suggested a link between sleep deprivation and hypertension, and that this link is stronger in women. Our laboratory recently reported that baseline sympathetic neural responses to total sleep deprivation (TSD) were different in young men and women, with a greater shift towards sympathetic predominance in young women. Postmenopausal women are at high risk for hypertension. In the present study, we hypothesize that TSD will alter sympathetic neural activity in older adults, with greater sympathoexcitation in postmenopausal women. Nine participants between the ages of 55 and 75 years (9 women and 7 men) participated in the study. Subjects were tested twice one month apart, once after 24‐hour TSD and once after normal sleep. Wrist actigraphy was worn 5 days prior to each testing to confirm normal sleep patterns. We recorded muscle sympathetic nerve activity (MSNA; microneurography), beat‐to‐beat blood pressure (finger plethsmography), and heart rate (electrocardiogram) during 5 min of supine, awake rest. TSD elicited divergent MSNA responses in older men and women. Specifically, MSNA burst frequency increased in postmenopausal women (31±3 to 35±3 burst/min), but not older men (39±3 to 36±4 burst/min; time × condition, p = 0.036). This shift towards sympathetic predominance in women was also observed when MSNA was quantified as burst incidence (time × condition, p = 0.034). TSD did not alter baseline mean arterial pressure (men, 89±5 to 87±3 mmHg; women, 84±4 to 84±3) or heart rate (men, 55±3 to 55±4 beats/min; 58±3 to 60±4 beats/min) in either group (time, p>0.05; time × condition, p> 0.05). In summary, 24‐hour TSD elicits divergent MSNA responses in older men and women, with greater sympathoexcitation in postmenopausal women. These findings provide new mechanistic insight into reported links between sleep deprivation and hypertension.Support or Funding InformationFunding support from the National Institutes of Health (HL‐122919) and Portage Health Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Liposome Encapsulated Vitamin C on the Cardiac Autonomic Response To A High‐Calorie Meal
Authors: Bell Christopher , Hanson Moriah Ruth , Fleck Joshua Robert , Grimm Nathan Carlisle 
Published: June 2021

Oxidative stress is adversely associated with heart rate variability and may be favorably modified with ingestion of antioxidants. The purpose of this study was to determine if prior ingestion of liposome encapsulated vitamin C favorably modifies the cardiac autonomic response to a high‐calorie meal. Ten young healthy adults (age: 26 ± 2 years, body mass index: 24.0 ± 1.4 kg/m2; blood pressure: 113/68 ± 3/2 mmHg; mean ± SE) ingested either a placebo or 5 g of liposome encapsulated vitamin C. Two hours later, they ingested a high‐calorie liquid meal (979 kcal; 30% fat, 64% carbohydrate, 6% protein). Circulating vitamin C concentrations, blood pressure and heart rate variability were measured over 6‐hours. Compared with placebo (0.7 ± 0.1 mg/dL), liposome encapsulated vitamin C ingestion appreciably increased circulating vitamin C (peak: 3.3 ± 0.1 mg/dL; P<0.01); concentrations remained high at 6‐hours (2.0 ± 0.1 mg/dL). Systolic blood pressure was increased following the meal however the magnitude of increase was lower with prior liposome encapsulated vitamin C (time × treatment interaction: P=0.019). Heart rate variability (standard deviation of R‐to‐R interval) was greater in the placebo compared with liposome encapsulated vitamin C (main effect: 104 ± 3 vs. 94 ± 3 ms; P=0.04) and decreased 1‐hour after the meal (main effect: 102 ± 5 vs. 87±5 ms; P=0.02); liposome encapsulated vitamin C did not influence this response (P=0.563). Similarly, the LF/HF ratio was greater with liposome encapsulated vitamin C compared with placebo (main effect: 7.3 ± 1.4 vs. 12.0 ± 1.4; P=0.041). Liposome encapsulated vitamin C appreciably increased circulating vitamin C concentration, favorably modified the systolic blood pressure response to a high‐calorie meal while potentially unfavorably modifying the heart rate variability response.Support or Funding InformationEmpirical LabsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TONIC GLUTAMATE NEUROTRANSMISSION BY NMDA RECEPTORS IN PARAVENTRICULAR NUCLEUS IS INCREASED IN CONSCIOUS RATS INDUCED TO 6‐OHDA PARKINSONISM
Authors: Martins‐Pinge Marli Cardoso , Amorim Eric Diego Turossi , Rodrigues Ananda Totti , Ariza Deborah , Crestani Carlos Cesar 
Published: June 2021

Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. In addition to the motor signals, PD patients present cardiovascular changes that appear to be accompanied by alterations in the autonomic nervous system. Recent data have shown that rats induced to Parkinsonism through bilateral administration of 6‐hydroxydopamine (6‐OHDA) in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR) compared to their controls, as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important structure for the integration of autonomic function and blood pressure (BP) control in the different behavioral and pathological situations. Thus, the aim of this study was to evaluate the role of PVN excitatory pathways in the cardiovascular and autonomic regulation during Parkinsonism induced by 6‐OHDA. Male Wistar rats were anesthetized and two guide cannulas were implanted into the PVN. 6‐OHDA or sterile saline was bilaterally administered directly into the SNpc. After 6 days and twenty‐four hours before the experiments, the animals were anesthetized and a polyethylene catheter was inserted into the abdominal aorta through the femoral artery and externalized dorsally to record MAP and HR in the conscious state. Administration of bicuculline (gabaA antagonist) in the PVN in sham group promoted an increase in MAP (Bic: 123 ± 7, baseline: 109 ± 5 mmHg) and HR (Bic: 435 ± 22, baseline: 355 ± 11 bpm). In the 6‐OHDA group, bicuculline exacerbated the increases in MAP and HR observed (MAP, 136 ± 3 mmHg; FC, 487 ± 8 bpm). Additionally, NBQX (non‐NMDA receptor inhibitor) did not promote changes in MAP and HR of the sham group, just as in 6‐OHDA group. On the other hand, microinjection of LY235959 (inhibitor of NMDA glutamate receptor) in the PVN of the sham group did not promote cardiovascular alterations, but in the 6‐OHDA group there was a decrease in MAP (LY: 83 ± 4, baseline: 98 ± 5 mmHg) and HR (LY: 251 ± 12, Baseline: 310 ± 14 bpm). Confirmation of 6‐OHDA lesion was observed by decreased levels (at least 70%) of dopamine in striatum. Our data suggest a role of NMDA receptors in the PVN, on tonic cardiovascular control of 6‐OHDA Parkinsonism in rats.Support or Funding InformationFundação Araucária; Capes (fellowship to EDTA); CNPq (Research fellowship to MCMP and CCC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intense Fear Induces Low‐Frequency Oscillation of Cerebral Blood Flow, Arterial Pressure, and Sympathetic Nerve Activity in Conscious Rats
Authors: Miki Kenju , Akiyama Yumiko , Ukita Hiroka , Nagao Kana , Kataoka Shizuka , Yoshimoto Misa 
Published: June 2021

A traumatic event, such as disaster, causes intense fear, which potentially leads to an increase in occurrence of cerebrovascular diseases. Little information is available regarding why intense fear causes cerebrovascular diseases. The present study aimed to measure cerebral blood flow, arterial pressure, and sympathetic nerve activity during intense fear conditioning in conscious rats. Wistar rats were chronically instrumented with a probe made with glass fiber for measuring hippocampal cerebral blood flow. Electrodes for measurements of renal (RSNA) and lumbar sympathetic nerve activity (LSNA) were inserted, as well as for an electroencephalogram, electromyogram, and electrocardiogram. A catheter was inserted for measuring systemic arterial pressure. Standard fear‐conditioning trials, in which a tone was paired with a brief electrical shock (5 mA, 2 s), were performed in rats two times per day over 3 days. Oscillation of arterial pressure with an amplitude of 15.7 mmHg and frequency of 0.075 Hz was induced by exposing a tone without electrical shock in fear‐conditioned rats. Arterial pressure oscillation was associated with synchronized oscillation of hippocampal cerebral blood flow, RSNA, and LSNA. Coherence between arterial pressure and hippocampal cerebral blood flow, RSNA, and LSNA was significantly increased at low frequency (0–1 Hz) compared with naive rats. These data suggest that intense fear can trigger disorder of sympathetic regulation of arterial pressure, causing low‐frequency oscillation of arterial pressure and synchronized changes in cerebral blood flow. This may be one of the causes of cerebrovascular disease induced by intense fear.Support or Funding InformationJSPS GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of High Fat High Fructose Diet on Peripheral Immune Cell Trafficking into the Brain in CCR2 Mouse Model
Authors: Sniffen Lindsey J. , Eidson Lori N. , Herrick Mary K. , MacPherson Kathryn P. , de Sousa Rodrigues Maria E. , Tansey Malu G. 
Published: June 2021

Recent studies about the gut‐brain axis suggest that high fat high fructose (HFHF) consumption is associated with chronic peripheral inflammation due to disruption of gut flora. Some evidence suggests that chronic peripheral inflammation may increase blood‐brain barrier (BBB) permeability. This may lead to increase in neuroinflammation and development of neurodegenerative diseases. The current study aims to observe the relationship between HFHF diet and BBB trafficking. We hypothesize that peripheral inflammation induced by HFHF diet will increase BBB permeability allowing for increased peripheral monocyte trafficking to the brain. To test this hypothesis, a mouse with red fluorescent protein (RFP) driven by the chemokine receptor 2 (CCR2), was treated with HFHF or control diet (CD) for five weeks to induce chronic inflammation. CCR2 is expressed on peripheral monocytes and to a lesser degree on microglia in the brain. To differentiate between resident microglia and brain infiltrating peripheral monocytes, tissue sections were stained with CD169, a marker specific for peripheral monocytes. Brain sections from CCR2‐RFP mice were stained by immunofluorescence in the hippocampal areas of CA1, CA3, and the dentate gyrus as these areas are affected in the neurodegenerative Alzheimer's Disease. CD169 and CCR2 stained cells were quantified using mean intensity to determine the effects of diet on infiltrating peripheral monocytes. In CA3, CCR2 CD mice presented with significantly decreased CCR2 and CD169 mean intensity as compared with WT CD mice (p=0.048, p=0.03). This may be because the Tg only has one allele of CCR2, permitting less trafficking than WT mice, which have two alleles. In CA1, there was a main effect of diet such that Tg HFHF treated mice showed a significant decrease in CD169 mean intensity compared to Tg CD (p=0.02). The low number of animals, the old age of the animals, and the time treated with diet may have impacted our findings. The current data did not support our hypothesis that HFHF diet increases peripheral trafficking across the BBB. Future directions include repeating this experiment with more animals, and treating the animals with HFHF diet for a longer period.Support or Funding InformationWork was funded by the NIH NIA RO1 RF1AG051514 (MGT) and the APS IOSP Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hyperoxia‐Induced Bronchopulmonary Dysplasia in Neonatal Rats Acutely and Chronically Alters the Control of Breathing
Authors: Mouradian Gary Charles , Argote‐Alvarez Santiago , Thuku Gabriel , Gorzek Ryan , Brannon Avonlea , Mui Amanda , Konduri Girija Ganesh , Hodges Matthew 
Published: June 2021

Infants born prematurely have immature lungs, and the neural mechanisms that control breathing are still developing. Premature infants often require supplemental oxygen therapy (hyperoxia) which acutely improves oxygen saturation but consequently leads to bronchopulmonary dysplasia (BPD; chronic lung disease in infants). Whether hyperoxia‐induced BPD also exacerbates the control of breathing is unknown. Thus, the major objective of this study was to elucidate the short and long‐term effects of hyperoxia‐induced BPD on the control of breathing. Sprague Dawley rat pups were exposed to room air (21% O2/Bal. N2) or hyperoxia (90% O2/Bal. N2) from postnatal day 0–10 (P0–10) and ventilation measured during room air (20 min) and hypoxic (10 min; 12% O2/Bal. N2) conditions at P10, 12, 14, 17, 21, 43, and 60 using plethysmography to test the hypothesis that hyperoxia‐induced BPD would decrease breathing stability and impair development of key brainstem respiratory nuclei. By P20, hyperoxic treated pups had significantly (p<0.05) reduced inspiratory (33%) and expiratory flow rates (24%) compared to control (normoxic‐reared) pups, consistent with BPD and pulmonary histologic data from prior publications. Minute ventilation in hyperoxia‐treated pups was significantly decreased (−20% of control) at P10 but increased thereafter while breathing room air (+50% of control; P12–14), and increased ~25% under hypoxic conditions (P12–14, 60, p<0.05). These changes were initially driven by significant increases in breathing frequency (P12–17; +20–46%) and later by increased tidal volume (P43–60; 50%). Room air and hypoxia breathing frequency variability was significantly lower by 20–35% from P10–21 and elevated by 70% at P60, respectively. Moreover, the cumulative histograms of breathing frequencies binned every 10 breaths/min were significantly different in room air and hypoxia conditions across all ages in hyperoxic pups compared to control pups. Preliminary analyses indicated tidal volume variability across room air and hypoxia is also significantly elevated acutely (P10) by 100% and chronically (P60) by 250% in hyperoxic pups compared to control pups. Additional preliminary data indicate increased expression of an astrocytic marker (GFAP) throughout brainstem respiratory nuclei in P60 rats perinatally treated with hyperoxia, consistent with astrogliosis. These data demonstrate significant and lasting anatomical and physiological changes to the brainstem and the neural control of breathing in a rat model of BPD, suggesting additional potential pathologies in human BPD patients.Support or Funding InformationChildren's Hospital of Wisconsin Research InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Developmental consequences of intra‐uterine exposure to cannabinoids: impact on the ventilatory system of newborns rats
Authors: Patrone Luis Gustavo A. , Bicego Kenia C. , Gargaglioni Luciane H. 
Published: June 2021

The endocannabinoid system is already present in the central nervous system in the early stages of embryonic development, including in areas responsible for respiratory control. Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. However, the relationship between marijuana use and ventilatory problems in the offspring is uncertain. Therefore, the present study evaluated the effects of exposure to cannabinoids during the gestational period on the respiratory control system in P6–7 and P12–13 male rats. To this end, osmotic pumps were implanted subcutaneously in pregnant female rats at embryonic day 0 and delivered vehicle or CB1 receptor agonist (WIN55,212–2, 0.5 mg/Kg/day) for 21 days. Ventilation (VE) of newborn was recorded during normocapnia and hypercapnia (7% CO2), as well as the O2 consumption (VO2). Our data showed a 15% increase of hypercapnic ventilatory response in P6–7 WIN‐treated animals during 7% CO2 due to a higher respiratory frequency and an increase of the respiratory equivalent. For P12–13 rats, WIN‐treated animals showed a hyperventilation (VE/VO2) in basal conditions and an increase hypercapnic ventilatory response (~20%) due to an increase in both tidal volume and respiratory frequency. No difference in VO2 was observed between groups for both ages. Our results suggest that a chronic and over activation of endocannabinoid system during gestation alters basal ventilation and CO2‐drive to breathing during neonatal period.Support or Funding InformationSao Paulo Research Foundation (FAPESP) and National Council for Scientific and Technological Development (CNPq)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduced HIF1a Signaling Enhances Apneas During Perinatal Development
Authors: Garcia Alfredo J. , Moody Elissa J. , Xiao Jason 
Published: June 2021

Immature neonatal breathing is characterized by the occurrence of periodic apneas that disrupt the breathing rhythm and cause intermittent hypoxia (IH). IH has been proposed as a factor that facilitates the development of respiratory control allowing for the transition from unstable to stable breathing rhythms where apneas no longer occur. In adults, IH increases hypoxia inducible factor 1a (HIF1a) signaling that remodels respiratory control and augments peripheral chemoreflexes. However, it is unclear whether HIF1a signaling contributes to the stabilization of immature neonatal breathing during the first days of perinatal life. To address this, we used whole body plethysmography to track perinatal development of breathing beginning at postnatal day zero (P0) in mice heterozygous for hypoxia inducible factor 1a (HIF1a+/−) and wildtype littermates (WT). At P0 we observed unstable breathing rhythms characterized by periodic apneas in both genotypes. However, in HIF1a+/− (n=4) apnea number was 50% greater and apnea duration was 172% longer when compared to the WT (n=3). Our ongoing experiments suggest that the switch to stable breathing rhythms occurs between postnatal days three and four. Our findings indicate that HIFa signaling is important to the of the neonatal breathing rhythm.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.