bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Amplitude of the Photopic Negative Response (PhNR) in the Ins2Akita Mouse Model of Type 1 Diabetes Mellitus
Authors: Fortepiani Lourdes Alarcon , Le Dung , Akimov Nikolay P , Sohn Jeong‐Hyeon , Rentería René C 
Published: June 2021

Diabetic retinopathy (DR) is a common, severe complication of diabetes mellitus. Current clinical detection of DR is based primarily on visible retinal vascular damage, and earlier detection of impending DR might allow earlier treatment to protect function. Recent studies in both animal models and humans with diabetes have shown that degradation of retinal ganglion cell (RGC) function occurs at an early stage, before visible vascular complications and before significant RGC loss. The photopic negative response (PhNR), obtained from full‐field electroretinogram (ERG) with photopic stimuli is thought to arise directly from RGC activity. Here, we hypothesized that PhNR amplitudes are reduced in a type 1 diabetic mouse model, the Ins2Akita mouse, which develops hyperglycemia by 5 weeks of age and visual function and ocular blood flow deficits early in the disease progression, before overtly visible vascular damage. Diabetic (male heterozygotes) and control (male WT littermates) mice were grouped according to age: young, adult, and old (5–6, 9–11, and 12–14 months of age, respectively). ERG recording was performed with 1.62 log cd/m2 white flashes over a constant 40 cd.s/m2 green background (Diagnosys Espion and ColorDome ganzfeld system) using gold ring contact lens electrodes (LKC Techniologies) under isoflurane anesthesia. Following 1 hour adaptation to the green background illumination, PhNR, a‐wave, and b‐wave amplitudes and implicit times were measured in response to 25 10‐msec flashes.The mean PhNR amplitude of the adult diabetic mice was 36% of their age‐matched controls (p < 0.01). For the old diabetic group, the mean PhNR amplitude was 49% of their age‐matched controls (p < 0.05). However, no significant difference was found in the young group. A‐wave amplitudes were decreased in the diabetic adult group, to a value only 41% of their age‐matched controls (p < 0.05). B‐wave amplitudes were decreased in the diabetic old group, to 35% of their age‐matched controls (p < 0.05). However, no significant difference was found among groups for PhNR, a‐wave, or b‐wave implicit times. Our results suggest that PhNR amplitude is altered relatively early in the Ins2Akita mouse model of diabetes. This suggests PhNR measurements could be used to detect diabetic retinopathy at earlier stages than the current clinical standard.Support or Funding InformationNIH R01 EY023290 and UIWRSO Faculty Development GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characteristics of the Cortical Silent Period in Individuals with and without Spinal Cord Injury
Authors: Sfreddo Hannah J , Wu Yu‐Kuang , Maher Matthew T , Limonta James , Levine Jonah M , Wecht Jaclyn , Harel Noam Y 
Published: June 2021

ObjectiveTo increase our knowledge of corticospinal excitability changes in persons with spinal cord injury (SCI) by comparing the cortical silent periods (CSPs) of persons with chronic, incomplete cervical SCI to the CSPs of able‐bodied (AB) volunteers.MethodsThe CSP is a corticospinal inhibitory response (1). It appears as gap in electromyographic (EMG) activity of a voluntarily contracting muscle due to transcranial magnetic stimulation (TMS) delivered to the motor cortex (see Figure A). We measured TMS‐induced CSPs in 5 participants with chronic, incomplete cervical SCI and 5 AB volunteers as an exploratory outcome of a larger study assessing the effects of non‐invasive stimulation in persons with and without SCI. EMG data was collected from the abductor pollicis brevis muscle of the dominant hand in each subject. We recorded a total of 139 CSPs in the SCI participants and 176 in the AB participants. Further analysis of 4 more SCI subjects and 10 more AB subjects is ongoing.ResultsThe preliminary results suggest that the average CSP duration of the SCI group (89 ± 34 ms) was less than that of the AB group (116 ± 30 ms). While statistically insignificant, (p = 0.230; Figure B), our results corroborate previous findings of shortened CSPs in persons with SCI (2). Moreover, the proportion of CSPs with at least one “interruption,” visualized as a momentary spike in EMG activity lasting 5–10 ms (see Figure C), was higher in the SCI group (14.48% of CSPs) than in the AB group (2.56% of CSPs; ns; Figure D).ConclusionsOur preliminary findings, of shorter CSP duration and higher frequency of CSP interruptions in subjects with SCI, may imply that cortical inhibitory pathways are damaged or less excitable in persons with SCI. CSP parameters may be valuable outcome measures in the study of SCI.Support or Funding InformationNew York Spinal Cord Injury Research Board (DOH01‐CARTID‐2015‐00037)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chronic systemic inflammatory challenge induced by LPS promotes cognitive impairment
Authors: Schirmbeck Gabriel Henrique , Da Ré Carollina Fraga , Seady Marina , Fróes Fernanda , Silva Sthefani Gomes , Taday Jéssica Hauschild , Gonçalves Carlos Alberto Saraiva , Leite Marina Concli 
Published: June 2021

Neuroinflammation is a major component in the progression of neurodegenerative diseases such as dementia, although is not its main initiator. Its been demonstrated that inflammatory activation of microglia and astrocytes promotes protein aggregation of amyloid plaques and tau tangles, leading to neuronal death through other mechanisms, such as excitotoxicity. Although many studies investigated the effect of systemic inflammation on the progression of dementia and amyloid plaques in genetic mouse models of Alzheimer's disease, is not clear if systemic inflammation can induce dementia per se.Methods90‐day Wistar rats were exposed to chronic inflammatory challenges with intraperitoneal injections of LPS in two doses (500 μg/kg and 250 μg/kg) or saline once a week, for a 16‐week period. Rats were euthanasied 24 h after last LPS injection. Behavioral evaluation was conducted through Open Field (OF) and Object Location Memory‐Test (OLM) for spatial memory assessment. Hippocampal S100B content was measured by ELISA, nuclear Nf‐κB was measured by western blot, and L‐[3H] glutamate uptake was analyzed.ResultsBoth groups receiving LPS presented impaired spatial memory in the 24 h OLM, which is characteristic of hippocampal degeneration in animal models of dementia, while OF shown no locomotor impairment. S100B protein remained unchanged between groups, and glutamate uptake was reduced only in LPS 500 μ/kg group. Nuclear fraction of Nf‐κB was increased in both LPS groups.DiscussionHere, we demonstrate that chronic peripheral inflammatory stimuli promote cognitive impairment in the absence of other underlying neurodegenerative causes, such as genetic background. Increased Nf‐κB in nucleus indicates hippocampal neuroinflammation, despite LPS challenge being peripheral. Besides, glutamate uptake was reduced in the higher dose of LPS, indicating a possible excitotoxic damage. Conversely, S100B content, which is an important biomolecule in inflammatory signaling, was not affected by LPS.Support or Funding InformationThis study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Apoio a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Denervation of carotid chemoreceptors decreases blood pressure in an ovine model of renovascular hypertension
Authors: Ramchandra Rohit , George Bindu , McBryde Fiona , Tromp Tycho , Chang Joshua 
Published: June 2021

BackgroundHypertension is a major health problem of pandemic proportions that is often inadequately controlled, warranting development of new treatments. There is increasing evidence that hypertension is initiated and maintained by elevated sympathetic nerve activity. There is also strong evidence that aberrant afferent signalling from carotid chemoreceptors promotes sympathoexcitation and hypertension. We hypothesized that hypertension is associated with activation of carotid chemoreceptors and that carotid sinus denervation (CSD) would reduce blood pressure.MethodsAdult ewes either underwent unilateral renal artery clipping or sham surgery. Three weeks later, baroreflex control of heart rate was examined and the contribution of sympathetic mechanisms to hypertension was determined using hexamethonium (125 mg/hr). The mean arterial pressure and renal blood flow response to activation of carotid chemoreceptors was determined in both groups. In a second surgery conducted in hypertensive animals only, the carotid sinus nerve was severed bilaterally (CSD) (n=6) or left intact (sham, n=6) and the effect on blood pressure was examined.ResultsUnilateral renal artery clipping induced hypertension (mean arterial pressure 109 ± 2 vs 91 ± 3 mmHg in shams, p<0.001). The pressor response and the renal vasoconstriction response to chemoreceptor activation was augmented in hypertensive animals compared to the normal group (for e.g. MAP response, 15 ± 1 vs 7 ± 2 mmHg, p<0.05). CSD decreased MAP (−17 ± 1 vs +2 ± 1 mmHg in shams, p<0.0001) and shifted the heart rate baroreflex curve to the left. The contribution of the autonomic nerves to hypertension was elevated in hypertensive animals compared to normal (−19 ± 2 vs −11 ± 2 mmHg, p<0.05) and CSD reduced this contribution.DiscussionIn conclusion, we have shown that hypertension in our large animal model is associated with activation of carotid chemoreceptors and that bilateral CSD lowers arterial pressure. Our data implicates the carotid chemoreceptors in the maintenance of renovascular hypertension.Support or Funding InformationFunded by the University of Auckland Faculty Research Development Fund and the Health Research Council of New Zealand.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ERYTHROPOIETIN NEUROPROTECTIVE PROPERTY AS NEW AS THERAPEUTIC TOOL FOR APNEA OF PREMATURITY
Authors: SOFIEN LAOUAFA , JOSEPH VINCENT , BAIRAM AIDA , SOLIZ JORGE 
Published: June 2021

We tested the hypothesis that Epo (Erythropoietin) protects newborns against the consequences of IH induced by apnea of prematurity (AoP). As caffeine (despite ineffective in about 50% of cases) is the treatment of choice of AoP, the effect of Epo and caffeine was compared.Male and female newborn rats exposed to IH during postnatal days (P) 3–10 were used in this work. During this time, animals were daily gavage with vehicle, Epo, caffeine, and Epo+caffeine (10–12 pups/group). At P10 the frequency of apneas and mean duration of apnea at rest were measured (as index of respiratory dysfunction induced by IH) plethysmography. Next, the hippocampus, cortex, and brainstem were harvested, and the activity of Superoxide‐Dismutase (SOD – major anti‐oxidant), Glutathion peroxydase (GPx) and NADPH oxidase (NOX – major pro‐oxidant) enzymes were evaluated.Our results showed that IH increased the frequency of apnea and mean duration of apnea in male and female, reduced SOD anf GPx activity, but increased NOX activity. Interestingly, Epo and caffeine significantly reduced apnea frequency, but only Epo efficiently restored the oxidant activity to normal levels. Moreover, the administration of Epo and caffeine together provided cumulative beneficial effects in reducing the apneic episodes in male and female pups.We conclude that Epo and caffeine activate different, but complementary mechanisms to decrease apneas, suggesting that combined Epo+caffeine treatment could be clinically relevant against AoP.Support or Funding InformationFounded by CIHR, Région Rhône alpes and consulat de France à Québec.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cellular Senescence in the Brainstem: Implications for Age‐Related Sympathetic Nervous System Dysregulation
Authors: Branen Lyndee , Balasubramanian Priya , Subramanian Madhan 
Published: June 2021

Aging is an independent risk factor for cardiovascular diseases such as hypertension and heart failure. Evidence from the literature suggests that sympathetic nervous system (SNS) dysregulation may play a causative role in age‐associated increased risk for cardiovascular diseases. The mechanisms underlying this phenomenon remains largely unknown. Senescent cells are known to accumulate in various tissues of the body with age and are implicated in the pathogenesis of several neurodegenerative diseases. Senescent cells are known to secrete cytokines, chemokines, and proteases through the acquisition of senescence‐associated secretory phenotype (SASP) and contribute to neuroinflammation in age‐related diseases. However, the presence of senescent cells in the brainstem, a region that contains several nuclei regulating sympathetic outflow and blood pressure has not been investigated. We hypothesized that senescent cells accumulate in the brainstem with age and promotes neuroinflammation, thereby contributing to age‐related SNS dysregulation. To test this, we isolated brainstem from young (2–4 months) and aged (24 months) male C57BL/6J mice (n=4–5/group) and performed gene expression analysis for cellular senescence markers and SASP using qPCR. Data were analyzed with students t‐test and expressed as mean ± S.E. Our results show significant increases in the mRNA expression of p16Ink4a (1.22 ± 0.4 vs 32.89 ± 8.78 fold, young vs aged, p<0.05) a well‐known senescence marker and pro‐inflammatory cytokines, and proteases like IL‐1β (1.03 ± 0.14 vs 2.13 ± 0.29 fold, p<0.05), MCP‐1 (1.02 ± 0.11 vs 4.33 ± 0.79 fold, p<0.05), IL‐1α (1.07 ± 0.2 vs 3.83 ± 0.73 fold, p<0.05, TNFα (1.06 ± 0.21 vs 4.48 ± 1.05 fold, p<0.05) and a trend for an increase in MMP3 in the aged brainstem, presenting evidence for senescence and SASP. We did not observe any age‐related changes in expression of metabotropic or ionotropic glutamate receptors, suggesting that the excitatory neurotransmitter machinery may not be altered in the brainstem with aging. Here we present, for the first time, evidence for cellular senescence in the brainstem of aged mice. Future studies will investigate the mechanistic role of senescence cells in the brainstem in age‐related SNS dysregulation.Support or Funding InformationRAC fund, CVHS, Oklahoma State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The neural control of arterial pressure by non‐catecholaminergic RVLM
Authors: Holloway Ben , Abe Chikara , Stornetta Daniel , Stornetta Ruth , Guyenet Patrice 
Published: June 2021

Tonic sympathetic nerve activity (SNA) is necessary for the maintenance of arterial pressure (AP) under anesthesia, and this tone is dependent on supraspinal input. Over the last two centuries, numerous studies have collectively identified the rostral ventrolateral medulla (RVLM) as a critical region for neural control of AP and SNA in anesthetized animals, however the relevance of these results to conscious animals and the nature of the RVLM neurons responsible remain conjectural. The RVLM has direct projections onto sympathetic preganglionic neurons, but the evidence that this is the critical pathway for AP regulation and SNA in conscious animals is not definitive—and even if this is the principal BP regulatory pathway of the RVLM, the bulbospinal neurons that produce these effects are still debated.Historically, the most prominent pressor candidate within the RVLM has been the rostral portion of the catecholaminergic C1 group. Rostral C1 neurons are glutamatergic, occupy a ventral region of the medulla that is coextensive with the vasomotor RVLM region, are barosensitive, directly innervate sympathetic preganglionic neurons, and activate sympathetic nerve discharge upon stimulation. Despite these data, optogenetic stimulation of C1 in conscious and anesthetized rodents has thus far failed to achieve the magnitude of increases in arterial pressure predicted by pharmacological stimulation of the RVLM.Here, we show that stimulation of a non‐catecholaminergic population within the RVLM is sufficient to increase AP in conscious mice, even after C1 lesion. We then targeted bulbospinal neurons using a retrograde virus and demonstrated that optogenetic activation of only bulbospinal RVLM neurons increases AP in conscious mice, and in anesthetized mice, stimulation increases AP and renal sympathetic nerve activity. Unlike optogenetic stimulation of C1 neurons, stimulation of non‐catecholaminergic bulbospinal RVLM causes robust and sustained increases in AP in both conscious and anesthetized states, and sustained increases in SNA under anesthesia. This data suggests non‐catecholaminergic bulbospinal neurons are powerful activators of AP and SNA and may play an important role along with C1 in arterial pressure maintenance.Support or Funding InformationAmerican Heart Association Predoctoral Fellowship; University of Virginia Wagner FellowshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Impact of Chronic Antioxidant Administration on Sympathetic Nervous System Activity and Vascular Function in Heart Failure Patients with a Reduced Ejection Fraction
Authors: Bunsawat Kanokwan , Ratchford Stephen M , Theisen Jeremy K , Park Soung‐Hun , Stehlik Josef , Wever‐Pinzon Omar , Drakos Stavros , Richardson Russell S , Wray D. Walter 
Published: June 2021

BackgroundHeart failure with reduced ejection fraction (HFrEF) is characterized by sympathetic nervous system (SNS) overactivation and vascular dysfunction, two important predictors of mortality and morbidity in this patient group. Importantly, oxidative stress, defined as an excess production of free radicals relative to antioxidant defenses, is prevalent in patients suffering from HFrEF. This pro‐oxidant state is associated with attenuated nitric oxide bioavailability, which may contribute to increased SNS activity and vascular dysfunction. While chronic oral antioxidant (AOx) administration has been documented to mitigate oxidative stress in other populations, the efficacy of this approach to improve autonomic and vascular function in patients with HFrEF has not been evaluated. Thus, this study sought to determine the effect of chronic (30‐day) over‐the‐counter oral AOx administration on SNS activity and vascular function in patients with HFrEF.MethodsFive HFrEF patients (71 ± 3 yrs; 28.5 ± 1.5 kg/m2) were studied before and after 30 days of oral AOx administration (Vitamin C, 1000 mg; Vitamin E, 600 IU; α‐lipoic acid, 600 mg; QD). Resting muscle sympathetic nerve activity (MSNA) was assessed for the determination of SNS activity, and vascular function was evaluated by brachial artery flow‐mediated dilation (FMD) testing. Venous blood samples were also collected for the direct determination of plasma free radical concentration (electron paramagnetic resonance spectroscopy, EPR).ResultsChronic antioxidant administration reduced MSNA burst frequency (pre: 44 ± 3 bursts/min; post: 38 ± 2 bursts/min, p<0.05). FMD appeared to improve following AOx administration (pre: 2.7 ± 0.7%; post: 4.0 ± 1.0%), but this change did not reach statistical significance (p=0.18). A tendency for a reduction in plasma free radical concentration following AOx administration (pre: 3.2 ± 1.6 AU; post: 0.7 ± 0.1, p=0.11) was also observed.ConclusionChronic antioxidant administration significantly reduced SNS activity and tended to improve vascular function, supporting the efficacy of this simple therapeutic approach to improve autonomic and vascular function in patients with HFrEF.Support or Funding InformationThis project is funded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001697, RX001418, E6910R).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Normobaric hyperoxia ameliorates renal ischemia reperfusion injury in rats
Authors: Nensén Oskar , Hansell Peter , Palm Fredrik 
Published: June 2021

IntroductionAcute kidney injury (AKI) represents an ever‐increasing clinical problem with high morbidity and mortality. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery. Renal hypoxia constitutes a common hallmark of AKI, and in the progression to chronic kidney disease (CKD). However, the role of hypoxia per se in the acute phase of renal injury remains largely unclear. The present study investigated 1) the role of systemic hypoxia in the acute progression and recovery of AKI, and 2) if normobaric global hyperoxia following AKI improves renal outcome.MethodsAnaesthetized (thiobutabarbital 120mg/kg i.p.) adult male Sprague‐Dawley rats were subjected to unilateral complete warm renal ischemia for 45 minutes followed by 2 hours of reperfusion under normoxic (21% inspired oxygen, n=10), hypoxic (10% inspired oxygen, n=10), and hyperoxic (60% inspired oxygen n=10) conditions. Kidney function, renal hemodynamics, intrarenal tissue oxygen tension (PO2), and renal oxygen consumption were estimated before and after the ischemic insult.ResultsAll investigated parameters were similar between groups at baseline. Animals subjected to 10% inspired oxygen developed intrarenal tissue hypoxia, whereas animals subjected to 60% inspired oxygen presented with increased intrarenal PO2 demonstrating that the approach to manipulate intrarenal tissue oxygen availability was successful. Furthermore, GFR at baseline were independent of renal tissue oxygenation.IR per se caused a steep decline in GFR in all groups (−97 ± 1, −87 ± 3, and −70 ± 11% for hypoxic, normoxic and hyperoxic animals, respectively), although renal blood flow and renal vascular resistance were similar before and after the ischemic insult. However, following IR there was a linear relationship between GFR and cortical PO2 when analysing all animals in all groups (Fig 1, linear regression P<0.05).ConclusionThis study demonstrates that renal function following IR is dependent on intrarenal oxygen availability. Furthermore, normobaric hyperoxia‐treatment initiated at the time of the ischemic insult has the potential to protect kidney function.Support or Funding InformationThis study was supported by the Swedish Research Council Medicine and Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.