The research program will use the latest technology for assessing neural activity, that of intrinsic optical imaging, together with single neuron and surface recording. The research plan will examine how rostral brain areas affect respiratory control during sleep in the development animal so that mechanisms of respiratory failure can be understood in victims of SIDS. State influences modify descending input from rostral brain regions to specific brainstem respiratory areas, and place the developing organism at risk for obstructive sleep apnea by differentially enhancing diaphragmatic over upper airway action.; the extent of rostral influences vary with development. Among rostral brain areas, the anterior hypothalamus/preoptic area exters substantial breathing influence by mediating thermal influences to respiratory sites. Sleep states can diminish or abolish descending thermal drive, thus blunting a large component of arousal-mediated upper airway muscle activation. We will examine the development of anterior hypothalamic neural activity to respiratory patterns at 3 ages in the kitten by 1) examining """"""""spontaneous"""""""" neural activity in the preoptic/anterior hypothalamus and in the motor column of branchial arch muscles during sleet and waking, and relating this activity to upper airway and diaphragmatic pattering, and 2) evoking activity in preoptic/anterior hypothalamic regions by environmental and local warming of the rostral brain site, and examining the resultant influences on local and brain stem neural interactions and overall activity will be assessed with intrinsic optical imaging procedures. Respiratory dependencies will be determined by cross- correlating cell discharge with patterning of the diaphragm and an upper airway dilator (the posterior cricoarytenoid); regression procedures will determine relationships with aspects of the respiratory cycle and with blood pressure. Evoked activity will include warming of the preoptic region to manipulate temperature """"""""drive"""""""" to respiration during each sleep-waking state, graded hypoxic and hypercapnic ventilatory challenges, and pharmacologic pressor stimulation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD001072-03
Application #
2194644
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1994-06-15
Project End
1999-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Tulane University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Gozal, D (2001) Central chemoreceptor function in children. Pediatr Pulmonol Suppl 23:110-3
Simakajornboon, N; Gozal, E; Gozal, Y M et al. (2000) Hypoxia induces activation of a N-methyl-D-aspartate glutamate receptor-protein kinase C pathway in the dorsocaudal brainstem of the conscious rat. Neurosci Lett 278:17-20
Gozal, D; Simakajornboon, N; Czapla, M A et al. (2000) Brainstem activation of platelet-derived growth factor-beta receptor modulates the late phase of the hypoxic ventilatory response. J Neurochem 74:310-9
Whitney, G M; Ohtake, P J; Simakajornboon, N et al. (2000) AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects. Am J Physiol Regul Integr Comp Physiol 278:R520-8
Gozal, D; Gozal, E; Simakajornboon, N (2000) Signaling pathways of the acute hypoxic ventilatory response in the nucleus tractus solitarius. Respir Physiol 121:209-21
Kreisman, N R; Soliman, S; Gozal, D (2000) Regional differences in hypoxic depolarization and swelling in hippocampal slices. J Neurophysiol 83:1031-8
Czapla, M A; Simakajornboon, N; Holt, G A et al. (1999) Tyrosine kinase inhibitors modulate the ventilatory response to hypoxia in the conscious rat. J Appl Physiol 87:363-9
Bandla, H P; Hopkins, R L; Beckerman, R C et al. (1999) Pulmonary risk factors compromising postoperative recovery after surgical repair for congenital heart disease. Chest 116:740-7
Menendez, A A; Nuckton, T J; Torres, J E et al. (1999) Short-term potentiation of ventilation after different levels of hypoxia. J Appl Physiol 86:1478-82
Gozal, E; Simakajornboon, N; Dausman, J D et al. (1999) Hypoxia induces selective SAPK/JNK-2-AP-1 pathway activation in the nucleus tractus solitarii of the conscious rat. J Neurochem 73:665-74

Showing the most recent 10 out of 44 publications