• Development of respiratory centers in the bullfrog tadpole brainstem

      Reed, Mitchell D.; O'Brien, Kristin; Taylor, Barbara; Harris, Michael; Drew, Kelly; Iceman, Kimberly (2017-08)
      Among vertebrates, rhythmic motor behaviors such as breathing, swallowing, and sucking are controlled by rhythm generators or neural oscillators located at various sites in the medulla of the brainstem. That all vertebrates exhibit these behaviors, leads investigators to hypothesize common ancestry for the cellular networks responsible for homeostatic rhythm generation in the brainstem. While the locations and functions of rhythm generating sites controlling some of these behaviors have been well investigated, details regarding the development of these sites remain largely unknown. Recent work has suggested that neural oscillators in the rostral and caudal medulla, which contribute to ventilation in amphibians, may be homologous with those controlling breathing in mammals. I first investigated the developmental contributions of these regions to CO₂ sensitivity and rhythm generation in bullfrog tadpoles at different stages of metamorphosis. I then characterized the function and structure of a neural oscillator essential for lung rhythmogenesis in the tadpoles and compared it to similar oscillators in mammals. To investigate functional aspects of brainstem, I used a combination of single-unit and whole-nerve electrophysiology in the presence of pharmacological agents (neuronal receptor agonists and antagonists) or following removal of portions of the isolated brainstem of bullfrog tadpoles at different stages of metamorphosis. Structural studies were accomplished using immunohistochemistry, staining for phenotypic markers common to mammalian rhythmogenic sites, and assessing the difference between early and late metamorphic bullfrog tadpoles. Taken together, my results suggest that amphibians may indeed have a rhythmogenic site in the rostral medulla that is homologous to a mammalian rhythmogenic site; it is both structurally and functionally similar to the mammalian parafacial respiratory group/retrotrapezoid nucleus complex. This region undergoes structural and functional changes as tadpoles develop through metamorphosis. Understanding the development of respiration in amphibians may provide clues into the evolution and development of breathing in mammals.
    • Methods of temperature & metabolism reduction in rats and possible influence on human health

      Bailey, Isaac R.; Drew, Kelly L.; Kuhn, Thomas B.; Rasley, Brian T. (2017-10)
      Spaceflight poses unique and significant hazards; the maintenance of human health remains a large part of the National Aeronautic and Space Administration (NASA) strategic goals and work remains to be done if we wish to maintain a long-term presence in space. The effects of ionizing radiation and bone density loss are some of the primary health related problems which need to be addressed. One of the main purposes of this research is to translate aspects of thermoregulation and metabolism reduction in hibernating species to a non-hibernating species in- order to devise alternative methods of preventing DNA damage and loss of bone density in astronauts. A second purpose for this research applies the same approach in emergency medicine, having potential as conjunctive therapy for cardiac arrest victims. Targeted temperature management (TTM; formerly known as therapeutic hypothermia) is the standard of care for these patients and is applied to increase survival rates and reduces neurological deficit. Stimulating Central Nervous System (CNS) A1 adenosine receptors inhibits shivering and non-shivering thermogenesis, inducing a hibernation-like response in hibernating species. A similar phenomenon occurs when using this technique in non-hibernating species such as rats. The adenosine A1 agonist, N6-cyclohexyladenosine (CHA) was utilized in all 3 of the experiments to determine how dose, diet, ambient temperature, and finally surface temperature affects the thermoregulatory response in Sprague-dawley rats. In addition to CHA, the partial agonist capadenoson was also tested for thermolytic efficacy (that is, the efficacy to abolish thermogenesis). Surface temperature control using a temperature controlled cage designed and built by myself in combination with IV CHA was found to be most effective in maintaining a target temperature of 32°C without risk of over-cooling. Results from these experiments suggests that the new standard technique in studying TTM using small animals should be similar to what is currently used in clinics; surface temperature modulation.