Visualizing anesthesia-induced vasodilation of cerebral vasculature using multi-exposure speckle imaging

AbstractAnesthetized animal models are used extensively during neurophysiological and behavioral studies despite systemic effects from anesthesia that undermine both accurate interpretation and translation to awake human physiology. In this paper, we characterize the impact of isoflurane on cerebral blood flow (CBF) during the induction of general anesthesia in awake mice using multi-exposure speckle imaging (MESI). We highlight the large anatomical changes caused by the vasodilatory inhalant with wide-field imagery and quantify the cortical hemodynamics with MESI across multiple subjects and imaging sessions. Compared to the awake state, we measured, on average, an 18% increase in surface vessel diameter accompanied by a 135% increase in vascular flux and 92% increase in parenchyma perfusion. These large alterations to the cortical vasculature and CBF are unrepresentative of normal physiology and provide further evidence that neuroscience experiments would benefit from transitioning to un-anesthetized awake animal models.

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Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

10.31234/osf.io/7gcuw ◽

2020 ◽

Author(s):

Jamie Lars Hanson ◽

Brendon Nacewicz

Keyword(s):

Animal Models ◽

Early Life ◽

Allostatic Load ◽

Child Poverty ◽

Past Research ◽

Early Life Adversity ◽

Stress Buffering ◽

Behavioral Studies ◽

New Findings ◽

The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load”, will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

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Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.624705 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jamie L. Hanson ◽

Brendon M. Nacewicz

Keyword(s):

Animal Models ◽

Early Life ◽

Allostatic Load ◽

Child Poverty ◽

Past Research ◽

Early Life Adversity ◽

Stress Buffering ◽

Behavioral Studies ◽

New Findings ◽

The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

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Impact of chronic outward force on arterial responses of proximal and distal of long superficial femoral artery stent

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02141-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hu Li ◽

Seung-Woon Rha ◽

Byoung Geol Choi ◽

Se Yeon Choi ◽

Sang Ki Moon ◽

...

Keyword(s):

Femoral Artery ◽

Superficial Femoral Artery ◽

Distal Segment ◽

Vessel Diameter ◽

Distal Portion ◽

Control Group ◽

Stent Restenosis ◽

Histopathologic Analysis ◽

Stent Diameter ◽

The Impact

Abstract Background Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. Methods In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. Results We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). Conclusions COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

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Consideration of Gut Microbiome in Murine Models of Diseases

Microorganisms ◽

10.3390/microorganisms9051062 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1062

Author(s):

Chunye Zhang ◽

Craig L. Franklin ◽

Aaron C. Ericsson

Keyword(s):

Animal Models ◽

Mouse Models ◽

Biomedical Research ◽

Gut Microbiome ◽

Close Association ◽

Disease Model ◽

Potential Contributor ◽

Potential Factors ◽

Models Of Disease ◽

The Impact

The gut microbiome (GM), a complex community of bacteria, viruses, protozoa, and fungi located in the gut of humans and animals, plays significant roles in host health and disease. Animal models are widely used to investigate human diseases in biomedical research and the GM within animal models can change due to the impact of many factors, such as the vendor, husbandry, and environment. Notably, variations in GM can contribute to differences in disease model phenotypes, which can result in poor reproducibility in biomedical research. Variation in the gut microbiome can also impact the translatability of animal models. For example, standard lab mice have different pathogen exposure experiences when compared to wild or pet store mice. As humans have antigen experiences that are more similar to the latter, the use of lab mice with more simplified microbiomes may not yield optimally translatable data. Additionally, the literature describes many methods to manipulate the GM and differences between these methods can also result in differing interpretations of outcomes measures. In this review, we focus on the GM as a potential contributor to the poor reproducibility and translatability of mouse models of disease. First, we summarize the important role of GM in host disease and health through different gut–organ axes and the close association between GM and disease susceptibility through colonization resistance, immune response, and metabolic pathways. Then, we focus on the variation in the microbiome in mouse models of disease and address how this variation can potentially impact disease phenotypes and subsequently influence research reproducibility and translatability. We also discuss the variations between genetic substrains as potential factors that cause poor reproducibility via their effects on the microbiome. In addition, we discuss the utility of complex microbiomes in prospective studies and how manipulation of the GM through differing transfer methods can impact model phenotypes. Lastly, we emphasize the need to explore appropriate methods of GM characterization and manipulation.

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Blending and obscuration in weak lensing magnification

Monthly Notices of the Royal Astronomical Society ◽

10.1093/mnras/stab539 ◽

2021 ◽

Author(s):

E Gaztanaga ◽

S J Schmidt ◽

M D Schneider ◽

J A Tyson

Keyword(s):

Systematic Errors ◽

Weak Lensing ◽

Wide Field ◽

Photometric Redshifts ◽

Field Surveys ◽

Systematic Effects ◽

The Impact ◽

Close Pairs ◽

Mass Profiles

Abstract We test the impact of some systematic errors in weak lensing magnification measurements with the COSMOS 30-band photo-z Survey flux limited to Iauto < 25.0 using correlations of both source galaxy counts and magnitudes. Systematic obscuration effects are measured by comparing counts and magnification correlations. We use the ACS-HST catalogs to identify potential blending objects (close pairs) and perform the magnification analyses with and without blended objects. We find that blending effects start to be important (∼ 0.04 mag obscuration) at angular scales smaller than 0.1 arcmin. Extinction and other systematic obscuration effects can be as large as 0.10 mag (U-band) but are typically smaller than 0.02 mag depending on the band. After applying these corrections, we measure a 3.9σ magnification signal that is consistent for both counts and magnitudes. The corresponding projected mass profiles of galaxies at redshift z ≃ 0.6 (MI ≃ −21) is Σ = 25 ± 6M⊙h3/pc2 at 0.1 Mpc/h, consistent with NFW type profile with M200 ≃ 2 × 1012M⊙h/pc2. Tangential shear and flux-size magnification over the same lenses show similar mass profiles. We conclude that magnification from counts and fluxes using photometric redshifts has the potential to provide complementary weak lensing information in future wide field surveys once we carefully take into account systematic effects, such as obscuration and blending.

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Intravitreal Anti-Vascular Endothelial Growth Factor Agents for the Treatment of Diabetic Retinopathy: A Review of the Literature

Pharmaceutics ◽

10.3390/pharmaceutics13081137 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1137

Author(s):

Irini Chatziralli ◽

Anat Loewenstein

Keyword(s):

Diabetic Retinopathy ◽

Vitreous Hemorrhage ◽

Fundus Photography ◽

Panretinal Photocoagulation ◽

Wide Field ◽

Vascular Endothelial ◽

Keywords Diabetic Retinopathy ◽

Anti Vegf ◽

The Impact

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. The purpose of this review is to gather the existing literature regarding the use of the approved anti-vascular endothelial growth (anti-VEGF) agents in the treatment of DR. Methods: A comprehensive literature review in PubMed engine search was performed for articles written in English language up to 1 July 2021, using the keywords “diabetic retinopathy”, “ranibizumab”, “aflibercept”, and “anti-VEGF”. Emphasis was given on pivotal trials and recent robust studies. Results: Intravitreal anti-VEGF agents have been found to significantly improve visual acuity and reduce retinal thickness in patients with diabetic macular edema (DME) in a long-term follow-up ranging from 1 to 5 years and are considered the standard-of-care in such patients. Regarding DR, intravitreal anti-VEGF agents provided ≥2-step improvement in DR severity on color fundus photography in about 30–35% of patients with NPDR at baseline, in the majority of clinical trials originally designed to evaluate the efficacy of intravitreal anti-VEGF agents in patients with DME. Protocol S and CLARITY study have firstly reported that intravitreal anti-VEGF agents are non-inferior to panretinal photocoagulation (PRP) in patients with proliferative DR (PDR). However, the use of new imaging modalities, such as optical coherence tomography-angiography and wide-field fluorescein angiography, reveals conflicting results about the impact of anti-VEGF agents on the regression of retinal non-perfusion in patients with DR. Furthermore, one should consider the high “loss to follow-up” rate and its devastating consequences especially in patients with PDR, when deciding to treat the latter with intravitreal anti-VEGF agents alone compared to PRP. In patients with PDR, combination of treatment of intravitreal anti-VEGF agents and PRP has been also supported. Moreover, in the specific case of vitreous hemorrhage or tractional retinal detachment as complications of PDR, intravitreal anti-VEGF agents have been found to be beneficial as an adjunct to pars plana vitrectomy (PPV), most commonly given 3–7 days before PPV, offering reduction in the recurrence of vitreous hemorrhage. Conclusions: There is no general consensus regarding the use of intravitreal anti-VEGF agents in patients with DR. Although anti-VEGF agents are the gold standard in the treatment of DME and seem to improve DR severity, challenges in their use exist and should be taken into account in the decision of treatment, based on an individualized approach.

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Nutritional programming of gastrointestinal tract development. Is the pig a good model for man?

Nutrition Research Reviews ◽

10.1017/s0954422410000077 ◽

2010 ◽

Vol 23 (1) ◽

pp. 4-22 ◽

Cited By ~ 172

Author(s):

Paul Guilloteau ◽

Romuald Zabielski ◽

Harald M. Hammon ◽

Cornelia C. Metges

Keyword(s):

Gastrointestinal Tract ◽

Animal Models ◽

Animal Studies ◽

Reference Model ◽

Human Subjects ◽

Mammalian Species ◽

Epidemiological Studies ◽

Long Term Effects ◽

Nutritional Programming ◽

The Impact

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

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Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

Clinical and Developmental Immunology ◽

10.1080/10446670410001722131 ◽

2004 ◽

Vol 11 (2) ◽

pp. 113-119 ◽

Cited By ~ 22

Author(s):

W. V. Kalina ◽

L. J. Gershwin

Keyword(s):

Animal Models ◽

Rna Virus ◽

Allergic Sensitization ◽

Upper Respiratory Tract ◽

Young Infants ◽

Wide Range ◽

Similar Disease ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

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