Henrik Lauridsen

Background/Objectives: Cardiac regenerative ability varies in vertebrates. Adult mammals cannot mount a regenerative response, while fetal mammals and some salamanders and teleosts fully regenerate the heart after a cryoinjury mimicking a myocardial infarction. This contrast is suggested to be regulated in part by metabolism, with high regenerative capacity correlating with a comparatively lower mass-specific metabolic rate, ectothermy rather than endothermy and a metabolic phenotype favoring glycolysis in cardiac muscle. Met hods: In this physiological study on axolotl salamanders, we altered the housing temperatures from the standard 20 °C to 10 °C, 25 °C and 30 °C and assayed key metabolic parameters as well as cardiac function, survival and regenerative capacity. Results: Our study demonstrated that while axolotls could be housed at temperatures ranging from 10 °C to 30 °C in an uninjured state, signs of a pathological response involving cardiac and metabolic insufficiency and mortality, especially after cryoinjury, increased progressively with increasing temperatures. We observed several metabolic effects, including differences in oxygen consumption, plasma metabolites and cardiac function. Cardiac regeneration after cryoinjury progressed as expected with only a small remaining injury after 60 days at the standard housing temperature of 20 °C. Regeneration was highly reduced in a reversible manner at 10 °C while regenerative rate was not affected at 25 °C. At 30 °C, cardiac regeneration could not be evaluated as the majority of animals (five out of six) did not survive the injury, likely reflecting insufficient cardiac reserve capacity to simultaneously sustain thermal metabolic effects and support tissue repair. Conclusions: The ectothermic axolotl undergoes several metabolic changes when exposed to different housing temperatures, with heart regeneration showing a narrower permissive temperature range than survival of the axolotl in an uninjured state.

A major threat to the declining European hedgehog (Erinaceus europaeus) is road traffic. Devising methods to reduce the number of collisions would increase hedgehog welfare in an urbanized world and serve to protect this flagship species, and this goal might be advanced by an understanding of their hearing. This study investigates the auditory capabilities and anatomy of the ear of the European hedgehog. Using auditory brainstem response testing on 20 live hedgehogs from Danish wildlife rescue centres, we measured hearing thresholds across 4–85 kHz and found a peak sensitivity around 40 kHz, revealing that European hedgehogs can hear sound frequencies of at least 4–85 kHz. Complementary postmortem micro-CT scans enabled a detailed three-dimensional reconstruction of the inner ear, revealing small middle ear bones with a cochlear spiral of approximately 1.7 turns. Results show that hedgehogs can perceive a broad ultrasonic range, which provides important cues for directional hearing and may additionally function in prey detection and communication. These findings provide critical insights into hedgehog sensory biology and inform the potential development of ultrasonic repellents to mitigate traffic collisions and habitat disturbances, contributing to conservation strategies for this declining species.

The axolotl is a popular model organism in regenerative biology owing to its ability to regenerate amputated limbs and internal organs. The role of injury-derived signals in initiating the regenerative response is still not well understood, but the potential involvement of the stress response is of interest, as injury and stress are temporally linked. The dominant glucocorticoid response to stress varies among species, with corticosterone generally considered dominant in most amphibians, whereas cortisol predominates in others. Here we characterize the adrenal stress response in the axolotl and describe methods to measure axolotl stress hormones to facilitate their inclusion in future research involving axolotl development and regeneration. We describe an intricate and unexpected axolotl stress response that involves cortisol and corticosterone, each being dominant under different conditions. Corticosterone is preferably activated by the classical hypothalamus–pituitary–interrenal axis pathway, with both arginine vasotocin and adrenocorticotropic hormone promoting its synthesis and release. Under manual stress and direct stimuli with acetylcholine, cortisol is more prominent, suggesting an alternative mechanism involving sympathetic nerve signaling. In response to an amputation injury, both cortisol and corticosterone are increased, with corticosterone being dominant, suggesting an injury-specific response. Finally, when administering glucocorticoids directly and measuring classical physiological effects of glucocorticoid signaling, cortisol is more potent. We propose a hypothesis that axolotls rely on cortisol as their dominant glucocorticoid, functioning in part as an extension of the catecholamine system. By contrast, corticosterone is mainly regulated classically via the hypothalamus–pituitary–interrenal axis.

Neural tissues are exceptionally sensitive to oxygen deprivation and rely on a dense network of blood vessels to support their extraordinarily high metabolic demands for oxygen, nutrients and clearance of waste products^1,2,3,4. In birds, one of the metabolically most demanding neural tissue—the retina—lacks internal blood vessels^5,6. This raises the question of how such a metabolically demanding neural tissue can function without blood perfusion. Here we show that, while the photoreceptor outer segments in the outer retina have access to oxygen, the inner bird retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons. We provide evidence that the pecten oculi—a uniquely vascularized structure in the vitreous humour of birds, the function of which has been debated for centuries^5,6,7,8,9—supplies the anoxic inner retina with glucose and removes lactic acid. We suggest that the pecten’s metabolic support of the bird retina’s anoxia tolerance enabled first the evolution of a thick cell-dense, avascular retina, which secondarily served as an exaptation enabling retinal function during high-altitude migrations.

Growth and remodeling of the cardiac outflow tract (OFT) is poorly understood but associated with serious congenital heart defects (CHD). While only a minority of CHDs have identifiable genetic causes, the functional roles of mechanical forces in OFT remodeling are far less characterized. A key barrier has been the lack of longitudinal investigations examining the interplay between dynamic blood flow and wall motion across clinically relevant stages. Here, we developed a live high-frequency ultrasound derived 4D moving-domain computational fluid dynamics (CFD) simulation approach, enabling longitudinal quantification of OFT hemodynamics and tissue mechanics in the same embryos across Hamburger-Hamilton (HH) stage 21 to HH27. We found that rising wall shear stress (WSS) strongly correlates with tissue extension in the distal OFT, whereas the proximal OFT experiences increasing expansive strains and higher hydrostatic stress with heartbeats. Additionally, we identified a double-helical flow pattern in the OFT lumen, possibly reflecting an evolutionary legacy for directing oxidized and non-oxidized blood flow before great vessel septation. Together, our results advanced insights in how hemodynamic forces and tissue stress contribute to OFT remodeling and septation.

Background: Diabetes is a group of diseases characterized by loss of β cell mass and/or function, resulting in hyperglycemia. With no established curative treatment, this has initiated research in β cell regeneration. Current animal models have either limited regenerative capacity (mice) or small size and evolutionary distance from humans (zebrafish). There is a need for new models to study endogenous regeneration pathways. This study proposes the axolotl salamander ( Ambystoma mexicanum ) as a model for studying the regeneration of β cells and aims to establish a protocol for STZ‐induced hyperglycemia to mimic a diabetic state. Results: In this pilot study, five streptozotocin (STZ) protocols were tested, and the most effective one was identified on the basis of glucose tolerance tests. Blood glucose levels were monitored to track both disease progression and remission. Histological examination of the pancreas and systemic effects of STZ treatment were also evaluated. Conclusion: Induction of a diabetes‐like state (hyperglycemia) in axolotls was possible with STZ, but variability among animals suggests the need for a higher degree of normalization or larger sample sizes. Histological regeneration was not observed, though blood glucose levels normalized over time. Some STZ‐treated animals developed edema, but its cause remains unknown.

Pregnancy toxemia is known from terrestrial mammals such as sheep and goats in which late-term twin-pregnant animals may enter a state of negative energy balance with compromised glucose homeostasis. Twin pregnancy is rare in seals, and pregnancy toxemia is undescribed. Herein, we describe a case from an almost 17-year-old harbor seal (Phoca vitulina, Linnaeus, 1758) raised in captivity. The seal died in stage 1 of labor after having experienced a 7- to 14-day period in which it refused to eat, but without any further clinical signs observed. The carcass was CT-scanned and necropsied. The most striking necropsy findings were a late-term twin-pregnant uterus that occupied most of the abdominal space, an abundant amount of fat, compressed and empty stomach and intestines, and diffuse hepatic steatosis. The imaging and necropsy findings indicate that the seal may have died as a result of pregnancy toxemia. As an incidental finding, a well-calcified os cordis was observed with CT, which may be due to the seal’s advanced age. This case thus represents three rarities: twin pregnancy, suspected pregnancy toxemia, and cardiac bone.

Background: The axolotl is a prominent model organism of heart regeneration due to its ability to anatomically and functionally repair the heart after an injury that mimics human myocardial infarction. In humans, such an injury leads to permanent scarring. Cardiac regeneration has been linked to metabolism and the oxygenation state, but so far, these factors remain to be detailed in the axolotl model. In this descriptive study, we have investigated metabolic changes that occurred during cardiac regeneration in the axolotl. Results: We describe systemic and local cardiac metabolic changes after injury involving an early upregulation of glucose uptake and nucleotide biosynthesis followed by a later increase in acetate uptake. We detect several promising factors and metabolites for future studies and show that, unlike other popular animal models capable of intrinsic regeneration, the axolotl maintains its cardiac regenerative ability under hyperoxic conditions. Conclusions: Axolotls undergo dynamic metabolic changes during the process of heart regeneration and display a robust reparative response to cardiac cryo‐injury, which is unaffected by hyperoxia.

The best practice for killing decapod crustaceans lacking a centralized ganglion has been debated for a century. Currently, there is a movement away from live boiling towards electrocution and mechanical splitting or spiking, which are efficient in the large commercial setting but may be unavailable and impractical for small decapods such as shrimp and prawn in the small-scale setting of, e.g., the household. Here, using carcasses of varying sizes of prawn, crayfish, lobster and green and brown crab, we used micro-CT imaging to measure surface area and sphericity in relation to body mass. Then, we measured heating profiles at the anterior ganglion and in the core of carcasses of the same species when exposed to standardized boiling regimes. We found a relationship with positive allometry between surface area and body mass for all species and a decrease in sphericity with mass. Heating times until proposed stunning (26 °C) and killing (44 °C) varied with body size and starting temperature and exceeded minutes for larger species. For a small species like prawn, times to stunning and killing by boiling are comparable to electrocution times and within the acceptable range compared to recreational killing of other sentient beings such as game mammals.