Stephen Johnson, MD / PhD
Department of Comparative Biosciences
Titles and Education
- M.D., Medicine, 1990 University of Iowa
- Ph.D., Physiology 1990 University of Iowa
- M.S., Biochemistry 1982 University of California at Riverside
- B.A., Biochemistry 1981 University of California at Riverside
Gestational intermittent hypoxia (GIH) alters breathing of neonatal offspring
Sleep disordered breathing (SDB) and obstructive sleep apnea (OSA) during pregnancy are growing health concerns because these conditions are associated with adverse outcomes for newborn infants. SDB/OSA during pregnancy exposes the mother and the fetus to intermittent hypoxia. Direct exposure of adults and neonates to intermittent hypoxia causes neuroinflammation and neuronal apoptosis, and exposure to intermittent hypoxia during gestation (GIH) causes long-term deficits in offspring respiratory function. However, the role of neuroinflammation in CNS respiratory control centers of GIH offspring has not been investigated. To address this question, pregnant rats are exposed to daily intermittent hypoxia during gestation (G10-G21). Neuroinflammation in brainstem and cervical spinal cord is evaluated in P0-P3 pups that are injected with saline or lipopolysaccharide (LPS; 0.1 mg/kg, 3 h). In CNS respiratory control centers, GIH attenuates the normal CNS immune response to LPS challenge in a gene-, sex-, and CNS region-specific manner. GIH also alters normal respiratory motor responses to LPS in newborn offspring brainstem-spinal cord preparations. These data underscore the need for further study of the long-term consequences of maternal SDB on the relationship between inflammation and the respiratory control system, in both neonatal and adult offspring.
• Johnson SM, Randhawa KS, Epstein JJ, Gustafson E, Hocker AD, Huxtable AG, Baker TL, Watters JJ. Gestational intermittent hypoxia increases susceptibility to neuroinflammation and alters respiratory motor control in neonatal rats. Respir Physiol Neurobiol Epub ahead of print, 2017.
Respiratory Rhythm Generation and Neuroplasticity – How does neuroinflammation alter breathing?
Breathing is a rhythmic motor behavior produced throughout our entire lifetime, but how neurons in the brainstem generate this behavior is not known. Also, breathing is highly modulated and can undergo long-lasting changes in rhythm frequency and motor output following activation of specific neurotransmitter receptors (respiratory neuroplasticity). We study isolated brainstems from neonatal rats and induce long-lasting increases in respiratory frequency (frequency plasticity) and long-lasting increases in spinal motor output (long-term facilitation). To test whether neuroinflammation alters respiratory neuroplasticity, neonatal rat pups are injected with lipopolysaccharide (LPS) to induce inflammation, and then isolated brainstems are tested to determine if respiratory neuroplasticity is altered.
Reptile Analgesia Without Respiratory Depression
In collaboration with Dr. Kurt Sladky (Surgical Sciences, UW School of Vet Med), our goal is to test and develop pharmacological approaches for providing pain relief in reptiles with minimal or no respiratory depression. To test for analgesic effects of drugs, noxious thermal stimuli are applied to the hindlimbs of awake turtles or to the ventral surface of snakes before and after drug administration. Breathing in awake turtles and snakes is measured to quantify any respiratory depression. Our major findings are that tramadol given orally produces long-lasting analgesia (up to 3 days after drug administration) with only modest respiratory depression in turtles. Surprising, snakes (corn snakes, ball pythons) are remarkably resistant to opioid drugs with respect to analgesia and possibly respiration. Snakes show no increase in noxious thermal withdrawal latencies with high dosages of morphine (40 mg/kg). When fentanyl patches were used to provide long-lasting therapeutic fentanyl levels, there was no increase in thermal withdrawal latencies, but modest respiratory depression was observed. Fortunately, dexmedetomidine (alpha2-adrenergic agonist) increases thermal withdrawal latencies without obvious anesthetic effects (several python behaviors were not altered by dexmedetomidine). However, dexmedetomidine also caused respiratory depression. Current studies are focused on testing whether co-administration of respiratory stimulant drugs with dexmedetomidine can induce analgesia without respiratory depression in snakes.
•Baker BB, Sladky KK, Johnson SM. Tramadol produces long-lasting analgesia with only mild respiratory depression in red-eared slide turtles (Trachemys scripta). J Am Vet Med Assoc 238: 220-227, 2011.
•Sladky KK, Kinney ME, Johnson SM. Analgesic efficacy of butorphanol and morphine in bearded dragons (Pogona vitticeps) and corn snakes (Elaphe guttata). J Am Vet Med Assoc 233: 267-273, 2008.
• Kharbush RJ, Gutwillig A, Hartzler KE; Kimyon RS, Gardner AN, Abbott AD, Cox SK, Watters JJ, Sladky KK, Johnson SM. Antinociceptive and respiratory effects following application of transdermal fentanyl patches and assessment of brain µ-opioid receptor mRNA expression in ball pythons. Am J Vet Res 78: 785-795, 2017.
• Bunke LG, Sladky KK, Johnson SM. Antinociceptive efficacy and respiratory effects of dexmedetomidine in ball pythons (Python regius). Am J Vet Res (in press).
- Veterinary Physiology A (fall semester)
- Veterinary Neuroanatomy-Neurophysiology (spring semester)
- Comparative Biomedical Sciences Training Program
- Neuroscience Training Program
Johnson SM, Randhawa KS, Epstein JJ, Gustafson E, Hocker AD, Huxtable AG, Baker TL, Watters JJ. Gestational intermittent hypoxia increases susceptibility to neuroinflammation and alters respiratory motor control in neonatal rats. Respir Physiol Neurobiol Epub ahead of print, 2017.
Kharbush RJ, Gutwillig A, Hartzler KE; Kimyon RS, Gardner AN, Abbott AD, Cox SK, Watters JJ, Sladky KK, Johnson SM. Antinociceptive and respiratory effects following application of transdermal fentanyl patches and assessment of brain µ-opioid receptor mRNA expression in ball pythons. Am J Vet Res 78: 785-795, 2017.
Bunke LG, Sladky KK, Johnson SM. Antinociceptive efficacy and respiratory effects of dexmedetomidine in ball pythons (Python regius). Am J Vet Res (in press).
- Johnson SM, Turner SM, Huxtable AG, Ben-Mabrouk F. Isolated in vitro brainstem-spinal cords are still useful tools in respiratory neurobiology. Respir Physiol Neurobiol 180: 1-7, 2012.