bluuebunny/crossref_metadata_2025_split huggingface dataset:
At-home void training with spinal epidural stimulation in an individual with chronic spinal cord injury using advanced customized software
Authors: Hubscher Charles , Wang Siqi , Johnson Erik , Cooke Christa , Christie Breanne , Tenore Francesco , Harkema Susan 
Published: May 2023

Bladder dysfunction is a highly prevalent quality of life issue in individuals with chronic spinal cord injury (SCI). The current study examined control of storage and emptying with neuromodulation in an SCI individual newly implanted with a spinal cord epidural stimulation (scES) electrode array. The goals of this pilot trial were 1) to enable dynamic human in-the-loop, sensor feedback, learning algorithm-controlled neuromodulation of micturition pathways in the home environment, and 2) to improve the transition from bladder storage to voiding in the home-setting by flexibly adjusting preset parameters in accordance with real-time physiological responses to bladder distention (e.g., sensations of fullness). Application of scES with a neurostimulator attached to a 16-electrode array was first examined in a controlled lab setting during filling cystometry by interactively identifying optimal stimulation parameters (cathode/anode configuration, stimulation frequency and amplitude) for storage and voiding. Efficacy was then tested in the lab for six-hour periods during natural bladder filling, followed by at-home use. The current report is on the first of four participants, a 40-year-old male T3 level of injury (AIS A) approximately 12 years post-injury, who entered the study having high filling pressures and low voiding efficiency. At-home daily training with scES (cohorts determined with prior in-lab mapping experiments) revealed effective storage at low fill pressure and efficient voiding, which improved over time. A major advantage of this system is afforded by the versatility of the multi-electrode array and technology advancements (STIMX) allowing for smooth transition from the storage to emptying phase, enabled by the ability to activate multiple spinal cord regions and associated functions with a single electrode placement and device using numerous cohorts simultaneously. Our next step is to develop a closed-loop, adaptive, real-time processing system that is used to automatically modulate epidural stimulation parameters based on acquired multi-modal sensor data. Funding provided by NIH Roadmap Initiative - Office of Strategic Coordination, Other Transactions, SPARC Program Award # OT2OD024898, University of Louisville Hospital, and Medtronic Inc. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Forearm vascular conductance responses to rhythmic handgrip in young African American compared with Caucasian American women
Authors: Nyarko Ruby , Liu Randy , Dalve Ashlesha , Perez Justo , Appiah Crystal , Van Wagoner Tyler , Kaur Jasdeep 
Published: May 2023

Non-Hispanic African American (AA) individuals have a disproportionately high prevalence, and mortality rate of cardiovascular disease (CVD) compared to other populations. Previous studies have demonstrated that even young, healthy AA individuals have blunted flow-mediated dilation, attenuated vasodilatory responses to pharmacological infusions and rhythmic handgrip exercise (RHG), as well as higher arterial stiffness and exaggerated peripheral vasoconstriction to isometric handgrip exercise and other non-exercise-stimuli compared to Caucasian-American (CA) individuals. These studies indicate that vascular alterations occur early on in life of AA individuals, potentially contributing to elevated risk of CVD in this racial group. However, these racial disparities in vascular function have almost exclusively been studied in men. Herein, we tested the hypothesis that, similar to young AA men, young AA women will exhibit an attenuated increase in forearm blood flow (FBF) and forearm vascular conductance (FVC) during rhythmic handgrip exercise (RHG) compared to age-matched CA women. Forearm blood flow (FBF; duplex Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography) were measured in young CA (n = 5) and AA (n = 5) women during rhythmic handgrip exercise performed at three workloads (15%, 30%, and 45% of maximal voluntary contraction (MVC)). FVC was calculated as FBF/MAP. Baseline FBF (CA: 66.0 ± 12.8 and AA: 61.6 ± 12.2 ml/min; mean ± SD, p = 0.30); FVC (CA: 0.8 ± 0.2 and AA: 0.7 ± 0.2 ml/min/mmHg; p = 0.16), MAP (CA: 82 ± 11 and AA: 88 ± 4 mmHg; p = 0.28), and MVCs (CA: 50 ± 4 and AA: 52 ± 5 kg; p = 0.35) were similar between the groups. Both groups exhibited intensity-dependent increases in FBF and FVC; however, contrary to our hypothesis, there were no race difference (mixed-model two-way ANOVA; FVC: race effect p = 0.18, intensity effect p < 0.0001, interaction p = 0.48). For instance, in response to RHG at 45%, CA had 384 ± 112% increase in FBF from baseline and AA had 499 ± 153% increase. Increase in FVC from baseline was 198 ± 76% for CA women and 314 ± 151% for AA women. MAP did not differ between the groups (e.g., ΔMAP at 45%; CA: 13 ± 11 vs AA: 9 ± 5, p = 0.41). These preliminary data suggest that the hyperemic response to rhythmic handgrip exercise in young African American women are similar to age-matched Caucasian-American women. Supported byKinesiology and Health Education UT Austin Start-up Account 19-2635-91. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Does increasing insulin resistance in adolescence actively decrease cerebral perfusion to oral glucose tolerance test?
Authors: Khademi Motlagh Hedyeh , Wannebo Brett , Ward Aaron , Bowlin Shawn , Eldridge Marlowe , Wieben Oliver , Livett Timothy , Carrel Aaron , Hermann Bruce , Jones Jana , Schrage William 
Published: May 2023

Background: Approximately 20% of American adolescents are obese, and nearly half demonstrate some form of insulin resistance (IR). Insulin acts as a metabolic hormone, a neurotrophic growth factor, and a vasodilator. Notably, adults with neurologic disease often exhibit IR and reduced cerebral blood flow (CBF). Adolescent brains are actively growing such that IR may negatively impact brain health in part due to lower brain perfusion. Specifically, given the role of insulin as a potential vasodilator, we hypothesized CBF would increase in response to a physiologic glucose-insulin surge, but this effect would lessen as IR level increased. Methods: Adolescents (n=11, 3 females, age=14.8±2 yr, BMI=24.7±7) taking no medications were studied. IR was estimated by calculating HOMA-IR using fasting glucose and insulin, spanning a spectrum of IR (excluding diabetes). Subjects completed a magnetic resonance imaging (MRI) study visit to assess cerebral perfusion using arterial spin labeling (ASL). Heart rate (HR), mean arterial pressure (MAP) and end tidal CO2 (ETCO2) were assessed at baseline and during oral glucose tolerance test (OGTT); ingesting 75g glucose in 296mL water (Trutol). Venous blood was sampled at baseline and 5, 10, 20, 30, 45, and 60 minutes post OGTT. Perfusion at peak plasma insulin was compared to baseline. Significance was determined using linear regression of change in perfusion (peak- baseline) versus HOMA-IR and set at p≤0.05. Results: Results are mean±SD. HR (p=0.9), MAP (p=0.22) and ETCO2 (p=0.75) were similar across HOMA-IR. MAP (p=0.44) and ETCO2 (p=0.15) did not change during OGTT at insulin peak. Peak insulin occurred at 44±13 min post OGTT (baseline: 8±4 vs. peak: 65±38 μU/mL, p=0.001). Glucose changed from 79±6 to 142±30 mg/dL at peak insulin (p=0.0005). There were no significant associations between HOMA-IR and changes in perfusion in gray matter (R2=0.06, p=0.43) and white matter (R2=0.07, p=0.13). There were no significant associations for the following regions: hippocampus, amygdala, thalamus, anterior and posterior insula, and precuneus (R2 all <0.2, p all >0.14). There was a trend toward negative regression in anterior cingulate gyrus (R2=0.25, p=0.11). Conclusions: These data suggest an OGTT does not acutely change brain perfusion at a global or regional level in adolescents, except possibly the anterior cingulate gyrus that is negatively impacted by increasing IR. The majority of present findings do not support our hypothesis that OGTT-mediated changes in cerebral perfusion are associated with IR in adolescents. NIH R21HD097510 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Brain Derived Neurotrophic Factor (BDNF) modifies endothelial Ca2+ signaling
Authors: Macarilla Christian , Choi Chung-Sik , Taylor Mark 
Published: May 2023

BACKGROUND: Preventing or reversing endothelial dysfunction is essential for preserving vascular homeostasis and staving off vascular disease. Previous findings from our lab suggest that maintaining a distinct profile of calcium (Ca2+) signals along the endothelial network is crucial for sustaining normal vascular function and structure, and progressive restriction of dynamic Ca2+ signals under chronic low-flow conditions precedes impaired vasodilation and vascular remodeling. Brain Derived Neurotrophic Factor (BDNF) plays a key role in maintaining brain plasticity and has recently been implicated in cardiovascular health, perhaps through direct action on the endothelial TrkB receptors. The goal of this study was to determine whether BDNF might exert its effects by altering the endothelial Ca2+ signaling profile. METHODS: Using confocal imaging, we assessed endothelial Ca2+ in Cal-520-loaded open mouse carotid arteries. RESULTS: Two concentrations of Both BDNF (2.2M x 10-9 and 2.2M x 10-6) and the selective TrkB agonist LM22A-4 (4.8 x 10-9 and 4.8 x 10-6) increased Ca2+ dynamics beyond baseline; LM22A-4 increased frequency of events while BDNF increased the amplitude of events. TrKB receptor inhibition with the antagonist ANA-12 appeared to reduce TrkB dependent Ca2+ changes. These findings suggest that activation of the TrkB receptor alters Ca2+ dynamics in ex vivo carotid arteries. Future work will aim to elucidate the contribution of internal and external sources of Ca2+ and determine the role of shear stress in BDNF release. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Hypoxia-Evoked Spinal Adenosine Kinetics in Rats with Chronic Spinal Cord Injury
Authors: Seven Yasin Baris , Michaelson Alysha , Parikh Komal , Mitchell Gordon 
Published: May 2023

Therapeutic acute intermittent hypoxia (tAIH) is emerging as a simple and effective means of improving motor function after spinal cord injury (SCI) and ALS. For example, daily AIH applied one-week after C2 spinal hemisection (C2Hx) improves breathing in rats. Unfortunately, studies using the same protocol with chronic cSCI (>8 weeks) report less robust recovery, except when the rats are pretreated with an adenosine 2A receptor antagonist. Pro-inflammatory conditions, such as those experienced after SCI, increase CNS extracellular adenosine concentrations. Guided by increased understanding of adenosinergic signaling mechanisms constraining AIH-induced phrenic motor plasticity, we aimed to determine real-time in vivo dynamics of extracellular adenosine in response to hypoxia in the ventral cervical spinal cord in intact and spinally injured rats. We used enzyme-immobilized micro-biosensors for real time enzymatic detection of extracellular adenosine in the mid-cervical spinal cord of intact rats and rats with chronic C2Hx (>8 weeks post-injury) during 5-min 13% O2, 1-min 9% O2 and 1-min 9% O2 + 4% CO2. Extracellular adenosine exhibits rapid kinetics with a time-constant of seconds, regardless of condition. Rats with chronic C2Hx were classified post hoc into 2 groups: normotensive (systolic blood pressure > 120 mmHg) and hypotensive (systolic blood pressure < 120 mmHg). Normotensive C2Hx rats had baseline adenosine levels comparable to intact rats; hypoxia-induced increases in adenosine were slightly reduced versus intact rats. On the other hand, hypotensive C2Hx rats had elevated baseline adenosine levels and almost completely diminished hypoxia-evoked adenosine increases. Hypercapnic hypoxia had minimal impact on adenosine levels during exposures, but lowered adenosine following each hypercapnic hypoxic episode. These results suggest that changes in cardiovascular hemodynamics in chronic SCI rats can alter basal tissue adenosine levels, possibly undermining the therapeutic efficacy of tAIH in the condition of chronic SCI. Further, hypercapnic hypoxia appears to minimize inhibitory effects of adenosine on tAIH-induced phrenic/diaphragm motor plasticity. Supported by: NIH HL147554, HL148030 & OT2OD023854 and the University of Florida McKnight Brain Institute This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The effects of sucrose and arsenic on muscular insulin signaling pathway differ between gastrocnemius and quadriceps muscles
Authors: Pánico Pablo , Velasco Myrian , Salazar Ana María , Ostrosky-Wegman Patricia , Hiriart Marcia 
Published: May 2023

Background: Muscle insulin resistance can originate from a sedentary lifestyle, hypercaloric diets or, the exposure to endocrine-disrupting pollutants such as arsenic. In skeletal muscle, insulin stimulates glucose uptake by translocating GLUT4 to the sarcolemma. This study aimed to evaluate the alterations induced by sucrose and arsenic exposure in vivo on the pathways involved in insulin-stimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles. Methods: Male Wistar rats were treated with 20 % sucrose (S), 50 mg/L sodium arsenite (A), or both (A+S) in drinking water for 8 weeks. The intraperitoneal insulin tolerance (ITT) test was on the seventh week of treatment. Quadriceps and gastrocnemius muscles were obtained after overnight fasting or after 30 min of intraperitoneal insulin injection. We assessed changes in GLUT4 translocation to the sarcolemma by cell fractionation and abundance of the proteins involved in GLUT4 translocation by Western blot. Results: Male rats consuming S and A+S gained more weight than control and A-treated animals. Rats consuming S, A, and A+S developed insulin resistance assessed through ITT. Neither treatments nor insulin stimulation in the quadriceps produced changes in GLUT4 levels in sarcolemma and Akt phosphorylation. Conversely, A and A+S decreased protein expression of Tether containing Ubx domain for GLUT4 (TUG), and A alone increased calpain-10 expression. All treatments reduced this muscle's protein levels of VAMP2. Conversely, S and A-treatment increased basal GLUT4 levels in the sarcolemma of the gastrocnemius, while all treatments inhibited insulin-induced GLUT4 translocation. These effects correlated with lower basal levels of TUG and impaired insulin-stimulated TUG proteolysis. Moreover, animals treated with S had reduced capn10 protein levels in this muscle, while A and A+S inhibited insulin-induced Akt phosphorylation. Conclusion: Arsenic and sucrose act through different pathways to impair GLUT4 trafficking, and the effects differ between the quadriceps and gastrocnemius. CONACYT-Fronteras #568492, DGAPA-PAPIIT-UNAM #IN20872 and DGAPA-PAPIIT-UNAM #IN205621 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Measurement of hippocampal arteriolar diameter and blood velocity in awake head-fixed mice
Authors: Williams Alexandra , White Carl 
Published: May 2023

Cerebral hypoperfusion is associated with neurodegeneration. However, the influence of disease on the microcirculation of specific brain regions is poorly understood. In the current study, we validated a technical approach that allows us to simultaneously image arteriolar diameter and blood velocity in the hippocampi of awake, head-fixed mice. The approach involved implanting a gradient-Index (GRIN) lens into the hippocampus and cementing it in place together with a steel head-fixation bar. Imaging was performed after 7-14 days recovery. On the day of imaging, we intravenously administered Alexa Fluor 633 hydrazide (1.25 mg/kg) to label arterioles, and after 90 minutes, secured the mice on a custom-built stage of a widefield fluorescence microscope. We measured blood velocity in parallel with vessel diameter by imaging fluorescent latex beads infused by tail vein cannulation. Vessel diameter and blood velocity were assessed in 14 vessels from 6 mice. Hypercapnia induces cerebral vasodilation and increases cerebral blood flow. In our experiments, inhalation of 10% CO2 caused a 12.1 ± 6% (mean ± SEM) increase in vessel diameter and a significant (P<0.01, student’s t-test) increase in blood velocity from 1.09 ± 0.1 to 1.73 ± 0.2 cm/s (mean ± SEM). These data demonstrate the feasibility of this approach to assess microvascular function and perfusion in highly localized brain regions. NIH grant (HL142906) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Does the cofilin pathway play a role in closure of the avian ductus arteriosus (Gallus gallus)?
Authors: Rippamonti Jessica , Dzialowski Ed 
Published: May 2023

The ductus arteriosus (DA) is an oxygen-sensitive embryonic blood vessel present in all developing amniotes. The DA connects the pulmonary artery to the aorta to shunt blood away from nonfunctioning lungs and toward the fetal respiratory organ. Increased arterial PO2 after birth or hatch initiates permanent closure of the DA. Permanent closure of this vessel upon birth or hatch establishes proper separation of the pulmonary and systemic circuits in the mammalian and avian neonate. Smooth muscle contraction is governed by myosin light chain kinase (MLCK), which stimulates increased cross-bridge cycling, and through increases in actin polymerization. Actin polymerization occurs in smooth muscle cells when globular actin (G actin) polymerizes to form filamentous actin (F actin), allowing for greater contractile strength. Regulation of actin polymerization in some blood vessels involves the cofilin pathway. P-21 activated kinase (PAK) regulates Lim kinase, which inhibits the actin depolymerizer cofilin. Activation of cofilin results in the severing of filamentous actin, leading to decreased tension of vessels. In this study we examined the role of the cofilin pathway in maintaining DA patency in the embryonic stage and subsequent constriction and closure during hatching in the chicken. Following Isoflurane inhalation, embryonic DA were excised from developing chickens and vessel tension was evaluated using wire myography. The DA were maintained in physiological saline solution and low oxygen conditions before being exposed to inhibitors of the PAK pathway followed by exposure to elevated oxygen. To examine the role of the cofilin pathway in DA physiology, we used IPA3 to inhibit P-21 activated kinase, and LIMKi3 and SR7826 to inhibit Lim kinase. Exposure to IPA3 did not alter baseline vessel tension or contraction in response to elevated oxygen. Inhibition of Lim kinase did not disrupt vessel tension or responsiveness to elevated oxygen levels. Our findings suggest that the cofilin pathway is not involved in regulating tension dynamics during the embryonic development and subsequent closure of the DA at hatching. This research was funded by Grant R15HL14887 from NIH-NHLBI. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
17-Hydroxyprogesterone caproate lowers angiotensin II type 1 receptor agonistic autoantibody and improves hypertension in early-onset preeclampsia
Authors: Amaral Lorena , McCray Morgan , Evans Kymberlee , Hines Dorianne , Campbell Nathan , Deer Evangeline , Herrock Owen , Turner Ty , Wallace Kedra , Ibrahim Tarek , Lawson Frances , Harrell Ariel , LaMarca Babbette 
Published: May 2023

Preeclampsia (PE), new onset hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation, affects 8% of all pregnancies in the U.S. and it is associated with progesterone deficiency, chronic inflammation, elevated angiotensin II type 1 receptor agonistic autoantibody (AT1-AA) and endothelial dysfunction. Currently, the early delivery of the feto-placental remains the best treatment for PE. Elevations in progesterone and T helper 2 cytokines favor the immunotolerance of the fetus during healthy pregnancy. Progesterone, through its receptors, stimulates anti-inflammatory and vasodilatory pathways. Therefore, this study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), lowers AT1-AA and inflammation while reducing maternal blood pressure in women with early-onset preeclampsia (EO-PE). PE women received 17-OHPC (250 mg, I.M.) and blood draws were collected before and after 17-OHPC treatment. Placentas were collected at the delivery. Progesterone and PIBF levels were 15.4 +/- 45.6 pg/mL (n=12), 14.4 +/- 1.0 ng/mL in PE (n=10), which significantly increased to 155+/-57.0 pg/mL, 16.39 +/-0.74 ng/mL (p< 0.05 vs. PE) in PE+17-OHPC (n=6). TNF-alpha and IL-6 were 41.3 +/- 3.9 pg/mL (n=8), 20.1 +/-7.9 (n=11) in PE, which decreased to 21.1+/-5.5 (n=6, p< 0.05 vs. PE), 5.2+/-2.1 in PE+17-OHPC (n=5). AT1-AA levels were 23+/-5.2 ΔBPM in PE (n=5), which significantly reduced to 2.1 ΔBPM in PE+17-OHPC (n=8, p< 0.05). 17-OHPC prolonged time of delivery beyond 72h on average and maternal blood pressure was 148 +/- 3.7 mmHg in PE (n=19), which significantly decreased to 136+/-4 in PE+17-OHPC (n=14, p< 0.05). In conclusion, 17-OHPC reduces AT1-AA and inflammation while improved blood pressure and maternal outcomes in response to early-onset preeclampsia. Supported by NIH grants RO1HD067541, 1U54GM115428, P20GM121334 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.