Biology subjects

Herigstad, M.

Publications and source records attributed to Herigstad, M..

8 recordsLinked to original sources

bioRxiv2026

A non-invasive method of air pollutant exposure in an avian model of development

Air pollution is a growing public health concern. The developing fetus is particularly vulnerable, with exposure during pregnancy linked to negative developmental health outcomes. Teratogenic studies rely on the use of model organisms, such as the chick embryo, a well- established model of human development. However, existing protocols for the exposure of chick embryos to gaseous and aerosol pollutants have financial and technical limitations. Here, we present a novel, non-invasive method for the long-term exposure of chicken embryos to a gaseous toxin, carbon monoxide (CO). Exposure is performed inside airtight incubation boxes, which can be used in a standard laboratory incubator. We demonstrate reliable dosing of precise internal CO concentrations up to 200ppm, using a simple volumetric approach. Following optimization of key incubation parameters, temperature and turning frequency, we determined the impact of the system on embryo viability and development. Closed box incubation caused minor developmental delay but had no effect on chick embryo viability. Internal oxygen concentrations remained above hypoxic levels. No significant effects of exposure up to 200ppm CO were observed on embryo viability, weight or developmental stage. In conclusion, we present a non-invasive, affordable, accessible and technically straightforward exposure method for air pollutant teratogenicity studies. This method can be applied to other model systems and organisms beyond the chick embryo as well as to other gaseous and aerosol toxins. Thus, the system offers a suitable platform for future research on teratogenic doses, mechanisms and effects of air pollutants.

pharmacology and toxicology↗

bioRxiv2026

Micro-CT: A reversible contrast-based protocol for non-destructive imaging of cardiac morphology in an avian model.

Microcomputed tomography (micro-CT) is a useful tool that can be utilised for 3D structural characterisation and volumetric quantification of small biological specimens. Its potential application is particularly valuable within the field of cardiac development, where phenotypic profiling at the whole organ, cell, and molecular level is often most informative within the same sample. Consequently, this study sought to develop a multimodal imaging protocol to enable 3D phenotypic characterisation of embryonic avian hearts (iodine-based contrast X-ray imaging) prior to immunohistochemistry-based cell and molecular analysis. Micro-CT parameters were tested to establish an optimal protocol for 3D analysis of embryonic cardiac specimens across multiple developmental timepoints. Optimised parameters provided reliable and reproducible 3D analysis of cardiac macrostructures. Sodium thiosulphate treatment of X-ray imaged hearts effectively reversed the iodine-based contrast stain whilst maintaining antigen availability of nuclear, membranous, and cytoplasmic targets in traditional downstream imaging studies. Together, this study demonstrates a robust and highly efficient multimodal imaging strategy to comprehensively characterise cardiac morphology in avian embryos and may serve as a versatile foundation for a broad range of bioimaging applications within the wider scientific community.

developmental biology↗

bioRxiv2024

Asbestos Mineral Fibre Exposure Significantly Affects Volatile Organic Compound Profiles of Mesothelial Cell Lines In Vitro

Malignant mesothelioma (MM) is a rare cancer caused by exposure to asbestos, this condition continues to represent a significant diagnostic and therapeutic challenge. Due to the long disease latency, non-invasive diagnostic modalities such as breath analysis may enhance MM early detection by identifying the disease specific pattern of volatile organic compounds (VOCs) in exhaled breath. In this study, solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) was used to extract VOCs from the headspace of two mesothelioma cell lines: MSTO-211H (biphasic mesothelioma) and NCI-H28 (epithelioid mesothelioma) in addition to MET-5a (non-malignant mesothelial cell line), following exposure to asbestos mineral fibers (actinolite, amosite, crocidolite and chrysotile) and a non-asbestos fiber control (wollastonite). Multivariate statistical analysis was applied to identify VOC-based biomarkers associated with asbestos exposure within the cell lines. Data confirms that exposure to mineral fibers (including the non-asbestos fiber control) induces significant alterations in the levels of as many as 24 VOCs in each cell line. This is the first study to investigate the impact of asbestos mineral fiber exposure on the VOC profile of MM cell lines. This may be relevant to studies involving mesothelioma patients, as these VOCs could also serve as indicators of asbestos exposure in individuals who have been exposed to asbestos.

cancer biology↗

bioRxiv2023

Impact of carbon monoxide on neural activation during a reaction time task

Individuals are routinely exposed to low-level carbon monoxide (CO), by factors such as ambient pollution and tobacco smoking. It is known that inhalation of high levels of CO have a detrimental impact on cognitive function. This study sought to investigate the impact of low-level CO exposure on central nervous system cognitive processing speed, using Blood Oxygen Level Dependant (BOLD) functional Magnetic Resonance Imaging (fMRI). The effects of low-level CO (raised up to 6ppm in exhaled air) on reaction times and fMRI activation maps were measured in healthy non-smoking participants. Participants received BOLD fMRI scans on two separate occasions (air and CO intervention days) and were scanned during the performance of a simple reaction time task. Results showed mean activation in cerebellum and motor cortex for all conditions. A significant reduction in BOLD response in the right temporal gyrus was found following CO inhalation, compared to the air control. Reaction times were significantly slower after CO exposure on the CO experimental day, but did not significantly change on the air control experimental day. This suggest that even low-level CO may impact both behavioural and BOLD fMRI outcomes.

neuroscience↗

bioRxiv2021

Impact of carbon monoxide on early cardiac development in an avian model

Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association. Here, we exposed chick embryos in ovo to CO at three different concentrations (1ppm, 8ppm, 25ppm) plus air control (4 protocols in total) for the first nine days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight and ventricular wall thickness. We found that heart weight was reduced for the low and moderate exposures compared to air, and that ventricular wall thickness was increased for the moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols. This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.

developmental biology↗

bioRxiv2017

Imaging seminiferous tubules - a 9.4T MRI mouse model

Fertility problems affect many couples. Research into male fertility commonly uses mouse models due to their availability and similar spermatogenesis to humans. A common target is the seminiferous tubules, the site of spermatozoa production, typically studied using biopsies and histological analysis. High-field Magnetic Resonance (MR) may offer a non-invasive alternative to investigate testicular function in infertility models. Here, we assess seminiferous tubules structure in sacrificed mice to determine the usefulness of MR compared to histology. Twelve mice (11 aged 35-57 days, one >9 months) were sacrificed and MR imaged at 9.4T with a Rapid Acquisition with Relaxation Enhancement sequence. Testes were scanned in situ for all mice, and excised in a subset of mice (n=4). A second subset of mice (n=4) had their testes selected for histological analysis. Seminiferous tubule diameter was measured manually from MRI and histology images. Custom image analysis scripts were created for the automated segmentation of seminiferous tubules and calculation of tissue volumes. All ex vivo and in situ images of testes exhibited clear outlines of seminiferous tubules. Ratio of total testis volume to volume of seminiferous tubules did not differ significantly between ex vivo and in situ measurements, and were similar in mature and younger mice. Both total testis volume and seminiferous tubule volume were larger in the mature animal. While histological slices trended towards larger average seminiferous tubules diameter than MRI images, we found no significant differences between MRI and histological measurements. High-field MRI can be used in a mouse model to assess testicular structure in situ. All volumetric measurements compared favourably with histological data. In situ scans also clearly showed identifiable extra-testicular tissues, such as epididymis and prostate tissues. The potential to image tissues associated with sperm maturation as well as spermatogenesis emphasises how MR could be a useful technique in mouse models of fertility, however further work is required to optimize tissue segmentation and validate this method for use in longitudinal studies. This type of measurement could be extended to human fertility studies in the future.

physiology↗

bioRxiv2017

Low-Level Carbon Monoxide Exposure Affects BOLD FMRI

Blood Oxygen Level Dependent (BOLD) FMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from e.g. smoking. This study aimed to probe the vulnerability of BOLD FMRI to CO and determine whether it constitutes a significant confound in neuroimaging and clinical trials. Low-level (6ppm exhaled) CO effects on BOLD signal were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). FMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. CO significantly dampened global BOLD FMRI signal during hypercapnia and visual cortex activation during visual stimulation. During fingertapping, CO reduced visual cortex activation but increased premotor cortex activation. Behavioural and physiological measures remained unchanged. We conclude that BOLD FMRI is vulnerable to CO, possibly through baseline increases in CBF, and suggest exercising caution when imaging populations exposed to elevated CO levels, e.g. with high smoking prevalence.

neuroscience↗

bioRxiv2017

Treating the lungs via the brain: Mechanisms underpinning improvements in breathlessness with pulmonary rehabilitation.

BackgroundBreathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (\"over-perception\"). Pulmonary rehabilitation has profound effects upon breathlessness, without influencing lung function. Learned associations can influence brain mechanisms of sensory perception. We therefore hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations, reducing \"over-perception\".\n\nMethodsIn 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during learned associations with a word-cue task (using functional magnetic resonance imaging), clinical, and psychological measures of breathlessness.\n\nResultsImprovements in breathlessness and breathlessness-anxiety correlated with reductions in word-cue related activity in the insula and anterior cingulate cortex (ACC) (breathlessness), and increased activations in attention regulation and motor networks (breathlessness-anxiety). Greater baseline (pre-rehabilitation) activity in the insula, ACC and prefrontal cortex correlated with the magnitude of improvement in breathlessness and breathlessness anxiety.\n\nConclusionsPulmonary rehabilitation reduces the influence of learned associations upon neural processes that generate breathlessness. Patients with stronger word-cue related activity at baseline benefitted more from pulmonary rehabilitation. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.

neuroscience↗