bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Permeability is increased in Cerebral Arteries from the Dahl S Model of Superimposed Preeclampsia
Authors: McClung Daniel , Maeda Kenji , Garrett Michael , Ryan Michael , Sasser Jennifer 
Published: June 2021

Preeclampsia is clinically defined as elevated blood pressure after 20 weeks gestation along with other major organ involvement, such as brain, renal, or liver. It impacts 3–8 % of pregnancies, and there is currently no cure other than delivery of the placenta. The mechanisms leading to preeclampsia are not fully understood; however, recent work by our laboratory showed that the pregnant Dahl S rat closely mimics women with preexisting hypertension that develop preeclampsia. Therefore, pregnant Dahl S rats can be utilized to better understand the pathophysiological mechanisms and consequences of superimposed preeclampsia. Impaired cerebral vascular function has been implicated as a potential mechanism contributing to the increased risk of neurological complications associated with preeclampsia. In this study, we tested the hypothesis that pregnancy induces vascular permeability in cerebral arteries in Dahl S rats. Female Dahl S rats were mated at 16–18 weeks of age, while age‐matched virgin littermates were used as controls (n=5 per group). Middle cerebral arteries were isolated on gestational day 19–21, cannulated with glass pipettes, and pressurized to assess arterial permeability by measuring the change in intravascular pressure over time. Starling's Law states that fluid flux across a vessel wall is the result of hydraulic pressures and oncotic pressures due to differences in osmolality. In our model, the oncotic pressure gradient across the vessel wall was 0 mmHg, leaving only hydraulic pressures to determine fluid flux; therefore, the rate in pressure drop measured inside an isolated vessel is an indirect assessment of vascular permeability. Isolated vessels were equilibrated at 37°C for 30 minutes in physiological salt solution and pressurized to 75 mmHg. The diameter of isolated arteries after equilibration was 162±11 μm and 157±11 μm in virgin and pregnant rats, respectively (p=0.51). Intraluminal pressure was recorded every 5 minutes for one hour. As shown in the figure, the drop in intravascular pressure is greater in vessels isolated from pregnant rats compared to the pressure drop in vessels from virgin rats (*p< 0.01 vs virgin, n=5). Over the 60 minute experimental period, there was a significant difference in the drop in pressure permeability between the virgin and pregnant Dahl S rats (24.4±5.0 mmHg vs. 50.2±3.7 mmHg, respectively, P<0.01, n=5). These data indicate that pregnancy increases cerebral arterial permeability in Dahl S rats.This 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 hypercapnia on the swallow‐breathing relationship in cats
Authors: Reed Mitchell , Huff Alyssa , Poliacek Ivan , Bolser Donald C. , Pitts Teresa 
Published: June 2021

Swallow‐breathing coordination is critical for maintaining a clear airway during the act of swallowing. Swallows can occur during all phases of breathing, however, they are primarily initiated during expiration. The interaction between central pattern generators for swallowing and breathing contribute to this phase preference. While hypercapnia has known effects on the breathing central pattern generator, the effects of elevated CO2 on swallow‐breathing coordination are unknown. We examined the influence of hypercapnia on swallow‐breathing phase preference in the cat. Swallowing was induced in anesthetized spontaneously breathing cats by injection of water into the oropharynx and experiments were conducted under conditions of room air, 5% CO2, or 10% CO2. Electromyogram activity was measured using bipolar electrodes inserted into laryngeal and pharyngeal muscles (mylohyoid, geniohyoid, thyrohyoid, and thyropharyngeus), parasternal muscles and costal diaphragm. In cats breathing room air, 71% of swallows occurred during expiration (E), 12% during inspiration (I), 10% during the transition from inspiration to expiration (I to E), and 7% during the transition from expiration to inspiration (E to I). Under hypercapnic conditions swallows occurred more frequently during inspiration with 80% (5% CO2) and 68% (10% CO2) occurring during either the I or the E to I phases of breathing, and 16% (5% CO2) and 25% (10% CO2) occurring during expiration. These preliminary results suggest hypercapnia may affect swallow‐breathing coordination by causing the initiation of swallow to occur in more inspiratory phases (I and E to I).Support or Funding InformationSupported by R00‐HL 111215, NIH HL 103415, and 1OT20D001983.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A new method for automated and unbiased classification of respiratory‐related electromyogram (EMG) and pressure waveforms
Authors: Sunshine Michael Daniel , Fuller David Dwight 
Published: June 2021

Respiratory muscle EMG activity recorded with intramuscular electrodes and pressure waveforms recorded using whole body plethysmography are common outcome measures in pre‐clinical studies of respiratory control in awake‐behaving animals. These methodologies produce complicated waveforms which are dynamically changing on short time scales. Indeed, it is rare for an awake rodent to breathe with the regular and “metronomic” pattern that often typifies breathing in anesthetized rodents and respiratory motor patterns observed in vitro. However, many studies in rodent models ignore the complex behavioral influences on respiratory waveforms, and only limited periods of “stable breathing” are chosen for detailed analyses. In ongoing studies, we are developing an unbiased, automated classification system to compare the features (e.g., amplitude, duration), frequency (number of occurrences), and patterning (presentation order) of respiratory‐related EMG and pressure waveforms. The detection algorithm weights specific features of each waveform including: peak‐to‐peak amplitude, time to peak amplitude, area under the curve, and total duration of the event. K‐means clustering is then used to separate the different waveforms into distinct groups. The algorithm was validated using pressure waveforms collected via whole body plethysmography or intramuscular diaphragm EMG in awake adult male rats. For both EMG and pressure data, the algorithm was able to detect and quantify the occurrence of distinct waveforms likely associated with sniffing and tidal breathing. The waveforms were automatically stratified based on waveform characteristics such as amplitude and rate of change (e.g., incrementing or decrementing patterns). This analysis revealed at least six distinct waveforms for both the pressure and EMG data. We conclude that the method can rapidly stratify and quantitate respiratory‐related waveform data in a completely unbiased manner.Support or Funding InformationT32‐HD043730 (MDS). SPARC OT2 OD023854 (DDF). 1 R01 NS080180‐01A1 (DDF)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of alterations in basal inspiratory motor output and chemical control of breathing in two Parkinson's Disease rat models
Authors: Solomon Irene C. , Tuchinsky Jacob J. , Brogan Anna , Wadolowski Robert M. 
Published: June 2021

Respiratory dysfunction in Parkinson's Disease (PD) patients manifests as a variety of altered breathing patterns that are suggested to result from impairment of central respiratory control. Experimental rodent (rat) PD models have been developed and studied in order to gain insight into both the motor and non‐motor symptoms that underlie PD; however, very few studies have focused on central respiratory deficits in any of these models. Ongoing work in our laboratory has begun to address this issue by characterizing the alterations in basal inspiratory motor output (tongue and/or diaphragm EMG activity) and chemical control of breathing in the 6‐hydroxydopamine (6‐OHDA) neurotoxin‐induced unilateral substantia nigra (SN)‐ and medial forebrain bundle (MFB)‐lesioned rat PD models. For these studies, experiments were conducted in spontaneously breathing urethane‐anesthetized adult female rats 2‐weeks after SN (n=6) or MFB (n=8) 6‐OHDA injections; control rats received vehicle injections (SN, n=5; MFB, n=5). Following recording of basal inspiratory‐related activity, rats were exposed to either hypoxic (12% O2 for 90s; HVR) or hypercapnic (7% CO2 for 5 min; HCVR) gas. Our preliminary data indicate that both SN‐ and MFB‐lesioned rats exhibited alterations in respiratory activity but the respiratory behaviors noted were not identical. Compared to control rats, SN‐lesioned rats exhibited (1) slightly higher basal breathing frequency; (2) similar HVR frequency increase; (3) attenuated HVR amplitude increase; and (4) similar HCVR frequency and amplitude increases. In contrast, MFB‐lesioned rats (compared to control rats) exhibited (1) similar basal breathing frequency; (2) slightly enhanced HVR frequency increase; (3) no change or a decrease in HVR amplitude; (4) markedly reduced or absent HCVR frequency increase; and (5) similar HCVR amplitude increase. While these 6‐OHDA site‐targeted PD models appear to exhibit differences in basal respiratory behaviors and chemical control of breathing deficits, our preliminary observations indicate that both SN‐ and MFB‐lesioned rats are viable models for studying respiratory abnormalities in PD. However, we suggest that it may be necessary to study multiple PD models to fully capture the ventilatory abnormalities seen in PD patients and identify the mechanisms that underlie these respiratory abnormalities.Support or Funding InformationNIH NS101737; Thomas Hartman Center for Parkinson's Disease Research at Stony Brook UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Maternal High Fat Diet Causes Changes in Pulmonary Function and Persistent Deficits in Pulmonary Vascularization
Authors: Heyob Kathryn M. , Mieth Saya , Lee Robert J. , Rogers Lynette K. 
Published: June 2021

BackgroundMaternal obesity has been associated with multiple complications for both the mother and the child including hypertensive disorders and gestational diabetes for the mother and macrosomia and congenital abnormalities for the child. Previously, we demonstrated increases in inflammation, deficits in alveolarization, and decreases in angiogenic pathways in the offspring (PN21) of mice maintained on high fat diets during pregnancy and lactation. For the current studies we tested the hypothesis that maternal obesity would impair lung function in the offspring and that angiogenic pathways would continue to be depressed into adulthood (3 mon).MethodsFemale mice were fed high fat diets (HFD) or control diets (CD) for 8 weeks prior to mating and through weaning. At weaning the pups were placed on either CD or HFD until 3 months of age. Pulmonary function was assessed using a Scireq Flexivent. Expressions of angiogenic pathway proteins were measured by western blot in lung tissues.ResultsAt 3 months, pulmonary function tests indicated decreased inspiratory capacity, resistance (Rrs), elastance (Ers) and airway resistance (Rn) in the offspring that were fed HFD after weaning. These finding were exacerbated in pups having been born to and nursed by mothers fed HFD. Protein expression of PTP1B was also suppressed at 3 months.ConclusionsMaternal and adult HFD results in altered pulmonary function at 3 months of age. Changes in pulmonary function may contribute to increased morbidities associated with obesity.Support or Funding InformationThe authors gratefully acknowledge funding from the NIH/NICHD, R01HD0880833.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of Corticotrophin Releasing Hormone in Paraventricular Nucleus in Elevated Sympathetic Outflow in Spontaneous Hypertension Rat
Authors: Zhou Jingjing , Ma Hui‐Jie , Li De‐Pei 
Published: June 2021

Corticotrophin releasing hormone (CRH) is one of the critical neuropeptides that regulate neuroendocrine and autonomic function. CRH expression level is significantly increased in the hypothalamic in patients with essential hypertension. However, the roles of CRH in the regulation of blood pressure and sympathetic outflow is unknown. We hypothesized that CRH and its receptors in the paraventricular nucleus (PVN) in the hypothalamus are involved elevated sympathetic vasomotor tone in essential hypertension. Arterial blood pressure basal (ABP), heart rate (HR), and renal sympathetic activity (RSNA) were recorded in anesthetized male adult spontaneous hypertension rats (SHR) and its normotensive control Wistar‐Kyoto (WKY) rats. Bilateral microinjection of CRH into the PVN dose‐dependently increased the ABP, HR, and RSNA in both SHRs and WKY rats. CRH‐induced sympathoexcitatory effect was significantly greater in SHR than in WKY rats and this effect was eliminated by microinjection of the CRH receptor 1 (CRHR1) specific antagonist NBI 35965 but not antisauvagine‐30, the specific antagonist for CRH receptor 2 (CRHR2). Bilateral microinjection of NBI 35965 into PVN significantly reduced the basal ABP, HR, and RSNA in SHR but in WKY rats. However, microinjection the antagonist antisauvagine‐30 into the PVN did not significantly alter ABP, HR, and RSNA in either SHR or WKY rats. Furthermore, the CRHR1 immunoreactivity was positive in retrogradely labeled PVN‐RVLM neurons. In addition, western blotting analysis revealed that CRHR1 expression levels in the PVN was significantly higher in SHR than in WKY rats. These data suggest that the enhanced CRH and its receptor function in the PVN is involved in elevated sympathetic drive in essential hypertension.Support or Funding InformationThis work was supported by the National Institutes of Health (Grants MH096086 to D.‐P. L.).This 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 Graded Sympathetic Activation on Regional Cerebral Vascular Conductance
Authors: Kaur Jasdeep , Barbosa Thales C. , Young Benjamin E. , Stephens Brandi Y. , Vranish Jennifer R. , Brothers R. Matthew , Fadel Paul J. 
Published: June 2021

The role of sympathetic nervous system in cerebral blood flow regulation remains poorly characterized. Previous studies have shown heterogeneity in regional cerebral circulation in response to various stimuli such as exercise, hypoxia, hypocapnia, etc. Recently, Ogoh et al. demonstrated that a moderate level (−50 Torr) of lower body negative pressure (LBNP) caused a significant reduction in internal carotid artery (ICA) blood flow, whereas vertebral artery (VA) blood flow remained unchanged, albeit trending towards a lower blood flow. Although a moderate increase in sympathetic nerve activity (SNA) occurs at −50 LBNP, it has been shown that SNA increases progressively with higher levels of LBNP. Whether VA blood flow is protected at higher levels of LBNP remains unknown. In this study, we tested the hypothesis that greater reflex‐mediated sympathetic activation via a higher level of LBNP will reduce conductance and blood flow to both the ICA and VA. In 9 young, healthy men, heart rate (ECG), arterial blood pressure (brachial sphygmomanometer), VA, ICA, and brachial artery blood flow (duplex Doppler ultrasound), middle cerebral artery (MCA) blood velocity (transcranial Doppler) and end‐tidal CO2 (ETCO2; capnograph) were measured at rest, and during 3–5 min of low, moderate and high LBNP (−30, −50, and −70 Torr, respectively). Conductance was calculated as blood flow of the respective artery/mean arterial pressure. Brachial artery blood flow and conductance were significantly reduced during all LBNP trials, indicating reflex‐mediated sympathetic vasoconstriction. Neither ETCO2 (Δ −1.9 ± 1.3 mmHg relative to baseline, p=0.18) nor any of the cerebral blood vessel measures were affected during −30 Torr LBNP. At −50 Torr LBNP, a reduction in ETCO2 (Δ −5.3 ± 1.6 mmHg relative to baseline, p=0.01) was accompanied by a reduction in ICA conductance (Δ −17.0 ± 8.4% baseline, p=0.057) whereas VA conductance remained unchanged (Δ −8.6 ± 5.6% baseline, p=0.24). Interestingly, with a similar reduction in ETCO2 at −70 Torr LBNP (Δ −4.3 ± 1.3 mmHg relative to baseline, p=0.04), there was a significant reduction in both ICA (Δ −13.1 ± 3.1% baseline, p=0.017) and VA conductance (Δ −20.4 ± 5.3% baseline, p=0.019). Thus, VA conductance was unaffected during low and moderate levels of LBNP however, high levels of LBNP induced a significant reduction in VA conductance and blood flow and this reduction appeared to be independent of the decrease in ETCO2. Collectively, these preliminary findings suggest that large increases in reflex‐mediated sympathetic activation via high levels of LBNP causes significant reductions in both ICA and VA conductance and blood flow.Support or Funding Information1 RO1 HL 127071This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A novel non‐invasive method to measure sympathetic activity and autoregulation in humans
Authors: Wilson Richard JA. , Jendzjowsky Nicholas , Steinback Craig , Tsai Willis H. , Herman Robert J. 
Published: June 2021

Current methods to assess sympathetic nervous system activity are associated with technical difficulty, invasiveness (microneurography) and poor temporal resolution ([plasma norepinephrine]). Use of heart rate variability overcomes most of these issues but is controversial because of limited accuracy. We have developed a quick, easy and non‐invasive approach based on spectral domain optical coherence tomography (OCT) that also allows investigation of arterial autoregulation. Here, we compare OCT and heart rate variability to microneurography, the gold standard of sympathetic assessment. We recruited 6 healthy males (26±3y) and 5 healthy females (23±1y), instrumented them for ECG and muscle sympathetic nerve microneurography and exposed them to respiratory and sympathetic provocations.Choroid vascular perfusion density (VPD) decreases with cold pressor test, inhaled hypoxia and breath‐hold, and increases with hyperoxia and hyperventilation suggesting that sympathetic activity dominates choroid responses. In contrast, retinal pigment epithelium VPD was unaffected by the cold pressor test, increased with hypoxia and breath hold and decreases with hyperoxia and hyperventilation, suggesting autoregulation dominates the retinal pigment epithelium. With regards to integrated muscle sympathetic nerve activity, heart rate variability had low predictive power whereas OCT was strongly (inversely) correlated (R= −0.91; p<0.01).These data suggest OCT may provide a novel approach to assessing autoregulation and sympathetic activity with superior predictability compared to heart rate variability. Given that sympathetic nervous system activity is a main determinant of autonomic function, sympathetic excitation is associated with serious cardiorespiratory/metabolic diseases and autoregulation is critical for brain health, we suggest that this new OCT technique will be of broad use to clinicians and researchers alike.Support or Funding InformationThis study was supported by Canadian Institute for Health Research (RJAW & WT). RJAW is an Alberta Innovates Health Solutions Senior Scholar. NGJ received postdoctoral salary support for this project from Alberta Innovates Health Solutions and the T Chen Fong 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.
Acute preoperative anti‐inflammatory treatment in a rat model for postoperative cognitive dysfunction; a role for the gut‐brain axis?
Authors: Schoemaker Regien G. , Hovens Iris B. , Falcao Salles Joana G. , de Haan Jacco J. , van Leeuwen Barbara L. 
Published: June 2021

BackgroundInflammation is considered a key factor in the development of post‐operative cognitive dysfunction (POCD). We hypothesize that acute preoperative anti‐inflammatory treatment with ibuprofen improves postoperative cognitive performance involving the gut‐brain axis in a rat‐model of POCD.MethodsMale Wistar rats of 3 and 23 months old were fasted and received one preoperative bolus of ibuprofen (15 mg/kg i.p.) or handling without intervention as control, 30 minutes before being subjected to major abdominal surgery. Before and 7 days after intervention, fecal samples were collected to analyse the gut microbiome. Subsequently, rats were tested in the open field, novel object‐ and novel location recognition test and Morris water maze. Microglial morphology (IBA‐1) and neurogenesis (Double cortin) were assessed by immunohistochemistry after sacrifice at day 14.ResultsIbuprofen treatment improved postoperative spatial memory but not spatial learning, and increased microglial activity and neurogenesis in the hippocampus. A principle coordinate analysis of the gut microbiome revealed a significant effect of age (p=0.001), no effect of Ibuprofen, but a significant interaction between these parameters (p =0.045). Microbiome richness appeared positively correlated to spatial learning, and negatively correlated to neurogenesis.ConclusionOur data indicate that preoperative ibuprofen treatment can selectively improve spatial memory. As this effect coincides with microglia activation and increased neurogenesis in the Dentate Gyrus of the hippocampus, we conclude that Ibuprofen may improve POCD by selectively interfering with hippocampal Dentate Gyrus function. Although gut microbiome parameters showed age‐, but not Ibuprofen‐related differences, associations with behavior and neurogenesis may support involvement of gut‐brain interactions in POCD.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.