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Browsing by Author "Hickman, Debra L."
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Item Acute Effects of Hypothermia and Inhalant Anesthesia on Ultrasonic Vocalizations and Neuroendocrine Markers in Neonatal Rats(American Association for Laboratory Animal Science, 2024) Lamont, Katherine A.; Boynton, Marcella H.; Hickman, Debra L.; Fletcher, Craig A.; Williams, Morika D.; Laboratory Animal Resource Center, School of MedicineNeonatal rodents undergo anesthesia for numerous procedures and for euthanasia by anesthetic overdose. However, data regarding whether neonatal anesthesia is humane are limited. Hypothermia (cryoanesthesia) is the most commonly used anesthetic protocol for neonatal rats 10 d of age or younger. However, hypothermia has recently been restricted in several countries due to perceived painful effects, including pain on rewarming. Minimizing the potential pain and distress of neonates in research is imperative, although very challenging. Traditional validated and nonvalidated behavioral and physiologic outcome measures used for adult rats undergoing anesthesia are unsuitable for evaluating neonates. Therefore, we investigated the effects of several anesthetic methods on neonatal rats by using the innovative objective approaches of noninvasive ultrasonic vocalizations and more invasive neuroendocrine responses (i. e., serum corticosterone, norepinephrine, glucose). Our results show that hypothermia leads to heightened acute distress in neonatal rats as indicated by prolonged recovery times, increased duration of vocalizations, and elevated corticosterone levels, as compared with neonates undergoing inhalational anesthesia. We demonstrate that inhalational anesthesia is preferable to cryoanesthesia for neonatal rats, and researchers using hypothermia anesthesia should consider using inhalational anesthesia as an alternative method.Item Bias in Rating of Rodent Distress during Anesthesia Induction for Anesthesia Compared with Euthanasia(2018-03) Baker, Brittany A.; Hickman, Debra L.; Department of Medicine, School of MedicineSelection of an appropriate method of euthanasia involves balancing the wellbeing of the animal during the procedure with the intended use of the animal after death and the physical and psychologic safety of the observer or operator. The recommended practices for anesthesia as compared with euthanasia are very disparate, despite the fact that all chemical methods of euthanasia are anesthetic overdoses. To explain this disparity, this study sought to determine whether perception bias is inherent in the discussion of euthanasia compared with anesthesia. In this study, participants viewed videorecordings of the anesthesia of either 4 rats or 4 mice, from induction to loss of consciousness. Half of the participants were told that they were observing anesthesia; the other half understood that they were observing euthanasia. Participants were asked to rate the distress of the animals by scoring escape behaviors, fear behaviors, respiratory distress, and other distress markers. For mice, the participants generally rated the distress as high when they were told that the mouse was being euthanized, as compared with the participants who were told that the mouse was being anesthetized. For rats, the effect was not as strong, and the distress was generally rated higher when participants were told they were watching anesthesia. Because the interpretation of distress showed bias in both species—even though the bias differed regarding the procedure that interpreted as distressing—this study demonstrates that laboratory animal professionals must consider the influence of potential perception bias when developing policies for euthanasia and anesthesia.Item Cohousing Male Mice with and without Segmental Bone Defects(American Association for Laboratory Animal Science, 2018-04) Rytlewski, Jeffrey D.; Childress, Paul J.; Scofield, David C.; Khan, Faisal; Alvarez, Marta B.; Tucker, Aamir T.; Harris, Jonathan S.; Peveler, Jessica L.; Hickman, Debra L.; Chu, Tien-Min G.; Kacena, Melissa A.; Biomedical Sciences and Comprehensive Care, School of DentistrySpaceflight results in bone loss like that associated with osteoporosis or decreased weight-bearing (for example, high-energy trauma such as explosive injuries and automobile accidents). Thus, the unique spaceflight laboratory on the International Space Station presents the opportunity to test bone healing agents during weightlessness. We are collaborating with NASA and the US Army to study bone healing in spaceflight. Given the unique constraints of spaceflight, study design optimization was required. Male mice were selected primarily because their femur is larger than females’, allowing for more reproducible surgical outcomes. However, concern was raised regarding male mouse aggression. In addition, the original spaceflight study design included cohousing nonoperated control mice with mice that had undergone surgery to create a segmental bone defect. This strategy prompted the concern that nonoperated mice would exhibit aggressive behavior toward vulnerable operated mice. We hypothesized that operated and nonoperated male mice could be cohoused successfully when they were cagemates since birth and underwent identical anesthetic, analgesic, preoperative, and postoperative conditions. Using quantitative behavioral scoring, body weight, and organ weight analyses (Student t test and ANOVA), we found that nonoperated and operated C57BL/6 male mice could successfully be housed together. The male mice did not exhibit aggressive behavior toward cagemates, whether operated or nonoperated, and the mice did not show evidence of stress, as indicated by veterinary assessment, or change in body or proportional organ weights. These findings allowed our mission to proceed (launched February 2017) and may inform future surgical study designs, potentially increasing housing flexibility.Item Development of a step-down method for altering male C57BL/6 mouse housing density and hierarchical structure: Preparations for spaceflight studies(Elsevier, 2018-05) Scofield, David C.; Rytlewski, Jeffrey D.; Childress, Paul; Shah, Kishan; Tucker, Aamir; Khan, Faisal; Peveler, Jessica; Li, Ding; McKinley, Todd O.; Chu, Tien-Min G.; Hickman, Debra L.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineThis study was initiated as a component of a larger undertaking designed to study bone healing in microgravity aboard the International Space Station (ISS). Spaceflight experimentation introduces multiple challenges not seen in ground studies, especially with regard to physical space, limited resources, and inability to easily reproduce results. Together, these can lead to diminished statistical power and increased risk of failure. It is because of the limited space, and need for improved statistical power by increasing sample size over historical numbers, NASA studies involving mice require housing mice at densities higher than recommended in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). All previous NASA missions in which mice were co-housed, involved female mice; however, in our spaceflight studies examining bone healing, male mice are required for optimal experimentation. Additionally, the logistics associated with spaceflight hardware and our study design necessitated variation of density and cohort make up during the experiment. This required the development of a new method to successfully co-house male mice while varying mouse density and hierarchical structure. For this experiment, male mice in an experimental housing schematic of variable density (Spaceflight Correlate) analogous to previously established NASA spaceflight studies was compared to a standard ground based housing schematic (Normal Density Controls) throughout the experimental timeline. We hypothesized that mice in the Spaceflight Correlate group would show no significant difference in activity, aggression, or stress when compared to Normal Density Controls. Activity and aggression were assessed using a novel activity scoring system (based on prior literature, validated in-house) and stress was assessed via body weights, organ weights, and veterinary assessment. No significant differences were detected between the Spaceflight Correlate group and the Normal Density Controls in activity, aggression, body weight, or organ weight, which was confirmed by veterinary assessments. Completion of this study allowed for clearance by NASA of our bone healing experiments aboard the ISS, and our experiment was successfully launched February 19, 2017 on SpaceX CRS-10.Item Effectiveness of the Glass Bead Sterilizer for Sterilizing Surgical Instruments(American Association for Laboratory Animal Science, 2022) Skiles, Beth; Johnston, Nancy A.; Hendrix, G. Kenitra; Hickman, Debra L.; Laboratory Animal Resource Center, School of MedicineSurvival rodent surgery requires the use of sterile instruments for each animal, which can be challenging when performing multiple surgeries on batches of animals. Glass bead sterilizers (GBS) are widely considered to facilitate this practice by sterilizing the tips of the instruments between animals. However, other disciplines have raised questions about the efficacy of the GBS, especially when used with surgical tools that have grooves or ridges that may contain organic debris. In this study, we evaluated the efficacy of the GBS to sterilize instruments commonly used in rodent surgery by intentionally contaminating a selection of instruments with a standardized bacterial broth inoculated with Staphylococcus aureus and Escherichia coli. As expected, a simple ethanol wipe was ineffective in sterilizing instruments in all treatment groups. An ethanol wipe followed by GBS was effective in sterilizing 82.5% (99 of 120) of the instruments. Our study suggests that the GBS may not be effective for consistent sterilization of surgical instruments.Item Effects of Age of Pups and Removal of Existing Litter on Pup Survival during Cross-Fostering between Multiparous Outbred Mice(American Association for Laboratory Animal Science, 2011-09) Hickman, Debra L.; Swan, Melissa P.; Laboratory Animal Resource Center, IU School of MedicinePeriparturient manipulation of mice is a valuable tool for modern research facilities. Although fostering and Caesarian section frequently are used to eradicate pathogens, an often overlooked use is to rescue poorly breeding strains of mice. Here we characterized the weaning success rates after fostering outbred pups of variable ages (younger than 24 h; 5 to 7 d; 10 to 12 d) with full or partial replacement of litters and multiparous dams. There were no significant differences between most groups when analyzed by full or partial replacement or age of donor pups as compared with control groups, in which pups were manipulated but returned to the birth dam or the birth dam was not disturbed. However, significant differences were associated with fostering of 10- to 12-d-old pups in combination with younger pups. Overall, these findings suggest that limiting fostering to pups that are within 48 h of age and age-matching litters when fostering are unnecessary.Item Effects of daily restraint with and without injections on skeletal properties in C57BL/6NHsd mice(Nature, 2017-06) Larsen, Rachel A.; Peveler, Jessica L.; Klutzke, Joshuah B.; Hickman, Debra L.; Aref, Mohammad W.; Wallace, Joseph M.; Brown, Drew M.; Allen, Matthew R.; Anatomy and Cell Biology, School of MedicineItem Effects of Music Enrichment on Individually Housed Male New Zealand White Rabbits(American Association for Laboratory Animal Science, 2018-10-25) Peveler, Jessica L.; Hickman, Debra L.; Laboratory Animal Resources, IU School of MedicineThe beneficial effect of music has been demonstrated in many species. Although commercially available music CDs intended for use with rabbits are available, these enrichments have not been critically evaluated to determine whether they reduce distress. In this study, we used an aging colony of male rabbits to evaluate how the provision of music enrichment affected the wellbeing of the colony. After 6 mo of music enrichment, the rabbits in the colony demonstrated a significant decrease in fecal cortisol, suggesting that their stress was reduced. Six months after removal of the music enrichment, the rabbits demonstrated a significant increase in fecal cortisol and the heterophil:lymphocyte ratio, suggesting that they werestressed. These findings suggest that music enrichment with a commercially available music discs for rabbits can be used toimprove the wellbeing of animals used in biomedical research.Item Effects of Various Commercially Available Enrichment Options on Handling and Chronic Stress Markers in Female ICR Mice(American Association for Laboratory Animal Sciences, 2019-03) Peveler, Jessica L.; Swan, Melissa P.; Wheeler, R'nld R.; Boehm, Christine A.; Hickman, Debra L.; Medicine, School of MedicineAlthough social housing of mice generally is preferred, mice must be individually housed in some situations. In these cases, enhanced attention to environmental enrichment is encouraged, but few studies assess the wellbeing of mice provided various enrichments. In this study, we used female ICR mice to evaluate enrichment strategies that encouraged natural behaviors including foraging, exercise, sheltering, and socialization. After 3 mo of exposure to the assigned enrichment strategy, wellbeing was assessed by evaluating behavioral and physiologic differences between groups. The results suggested that the use of red-tinted igloos may decrease markers of mouse wellbeing. However, none of the selected strategies yielded measures of wellbeing indicating improvement as compared to individually housed mice with no enrichment (negative control). Furthermore, measures were not significantly different between paired mice and individually housed mice with no enrichment.Item Endpoints for Mouse Abdominal Tumor Models: Refinement of Current Criteria(American Association for Laboratory Animal Science, 2009-06) Paster, Eden V.; Villines, Kimberly A.; Hickman, Debra L.; Laboratory Animal Resource Center, IU School of MedicineAccurate, rapid, and noninvasive health assessments are required to establish more appropriate endpoints in mouse cancer models where tumor size is not easily measured. We evaluated potential endpoints in mice with experimentally induced peritoneal lymphoma, an abdominal tumor model, by comparing body weight, body condition, and behavior with those of a control group of mice not developing lymphoma. Our hypothesis was that body weight would increase or plateau, whereas body condition and behavioral scores would decrease, as disease progressed. Results indicated that body weight did not differ significantly between the control and experimental groups, but the experimental group experienced significant decreases in both body condition and behavioral scores. Our results support the use of body condition and behavioral scoring as adjunctive assessment methods for mice involved in abdominal lymphoma tumor studies in which health may decline despite an increase or plateau in body weight.
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