Biomedical subjects

David Gozal

Publications and source records attributed to David Gozal.

At least 37 records · Page 2Linked to original sources

PubMed2006

Cerebral oximetry improves detection of sickle cell patients at risk for nocturnal cerebral hypoxia.

We previously used cerebral oximetry to identify low cerebral venous oxygen saturation in waking children with sickle cell disease (SCD). Because arterial oxyhemoglobin desaturation is common during sleep in SCD patients, this study compared both waking and sleeping systemic arterial and cerebral venous oxygenation dynamics in children with and without SCD. Seventeen African-American (AA) children with homozygous SCD [8 (4-15) years; 29% male; normal transcranial Doppler velocities] were compared with a control cohort (CON) comprised of six healthy AA children [9 (4-16) years, 33% male]. Standard all-night polysomnographic recordings were performed, including measurement of arterial oxygen saturation by pulse oximetry (SpO(2)). Regional cerebral oxygen saturation (rSO(2)) was measured non-invasively with cerebral oximetry. Intra-cohort comparisons examined the influence of sleep on SpO(2) and rSO(2) in the subjects. Inter-cohort comparisons of SpO(2), rSO(2,) and the rSO(2)/SpO(2) ratio assessed the impact of SCD on systemic and cerebral oxygenation during wakefulness and sleep. Cohort differences in SpO(2) were not statistically significant in either wakefulness or sleep. However, only in the SCD cohort was the magnitude of SpO(2) change statistically significant (P = 0.002). In contrast, both waking and sleep rSO(2) cohort median values did differ significantly [awake: CON 76 (67-86) vs. SCD 62 (58-71), P = 0.01; sleep: CON 65 (60-77) vs. SCD 55 (48-61), P = 0.01)]. The waking rSO(2)/SpO(2) ratio was also significantly lower in the SCD group [CON 0.78 (0.68-0.88) vs. SCD of 0.66 (0.61-0.72); P = 0.015]. During sleep, the ratio was also significantly lower in the SCD group [CON 0.71 (0.66-0.81) vs. SCD 0.59 (0.52-0.65); P = 0.011]. Our findings suggest that SCD patients may be at increased risk of cerebral hypoxia during both wakefulness and sleep.

Adolescent↗

PubMed2006

Urinary F2-isoprostane metabolite levels in children with sleep-disordered breathing.

Oxidant stress-related mechanisms have been proposed as a major contributor to the increased prevalence of cardiovascular morbidity in adult patients with sleep-disordered breathing. Isoprostanes provide a reliable biomarker of oxidant injury in vivo. The purpose of the present study was to examine the hypothesis that oxidant stress, as evidenced by increased levels of F2-isoprostane metabolites (IsoP-m) in urine, is present in children with a spectrum of sleep-disordered breathing. Assays were performed on urinary samples obtained from each of 47 pediatric patients immediately upon awakening after standard overnight polysomnography. Of the subjects, 15% had mild, 9% had moderate, and 6% had severe sleep-disordered breathing. After controlling for correlations between BMI and IsoP-m and SpO2 values, IsoP-m values were unrelated to any polysomnographic measures. The absence of increased levels of urinary F2-isoprostane metabolites in children with sleep-disordered breathing suggests that oxidative stress is not a significant feature of pediatric sleep-disordered breathing.

Body Mass Index↗

PubMed2006

Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy.

OBJECTIVE: To investigate the relative contribution of various risk factors to the surgical outcome of adenotonsillectomy for obstructive sleep apnea syndrome in children. STUDY DESIGN: Children (n = 110; mean age, 6.4 +/- 3.9 years) underwent two polysomnographic evaluations before and after adenotonsillectomy. In addition, 22 control children were studied. History for allergy and family history of sleep-disordered breathing was taken before each polysomnographic evaluation. RESULTS: Significant changes in sleep stage percentages and sleep fragmentation were found in the postsurgery study compared with the presurgery study; 25% of the children had apnea/hypopnea index (AHI) </=1, 46% had AHI >1 and <5, and 29% had AHI >/=5 in the postsurgery study. The frequency of subjects with AHI </=1 after surgery was significantly lower among obese subjects (P < .05). Comparison between the children who had AHI </=1 after surgery and 22 control children showed complete normalization of sleep architecture after surgery. CONCLUSIONS: Adenotonsillectomy yields improvements in respiratory abnormalities in children with obstructive sleep apnea syndrome. Complete normalization occurs in only 25% of the patients. Obesity and AHI at diagnosis are the major determinant for surgical outcome. When normalization of respiratory measures occurs after surgery, normalization of sleep architecture will also ensue.

Adenoidectomy↗

PubMed2006

Toddler behavior following polysomnography: effects of unintended sleep disturbance.

STUDY OBJECTIVES: Childhood sleep disorders are consistently shown to affect behavior and cognition, but first-night effects on these measures are generally unknown. We sought to examine how sleep in the home versus the laboratory differed among healthy toddlers and how such differences relate to standardized scores on assessments the morning following polysomnography. DESIGN, SETTING, AND PARTICIPANTS: Twenty healthy 14-month-olds wore actigraphs during nighttime sleep at home for 5 nights preceding and during standard overnight laboratory polysomnography. The Bayley Scales of Infant Development (BSID-II) were administered once the morning after polysomnography. MEASUREMENTS AND RESULTS: All subjects had normal polysomnography. Sleep-start times at home and during polysomnography did not differ, whereas, during polysomnography, subjects awoke earlier (p = .008, d = .58), their total sleep time (p <. 001, d = 1.1) and sleep efficiency (p = .004, d = .57) were reduced, and they had shorter sleep-bout lengths (p = .004, d = .03), less immobility (p = .003, d = .62), and greater average activity during sleep (p <. 001, d = .98). Standardized assessments were not affected by differences between home and polysomnography night sleep, but children with greater emotional regulation difficulty had a lower percentage of immobility (r = -0.67, p = .001) and increased sleep fragmentation (r = -0.60, p = .005) during polysomnography. CONCLUSIONS: Although sleep-onset times were preserved, sleep in the laboratory was disrupted, compared with at home. These differences did not affect standardized scores, but the magnitude of the difference was associated with worse emotional regulation. The effects of sleep disturbance during polysomnography, or the influence of poor emotional regulation on sleep in the laboratory, should be considered in studies of young children.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Correlates of sleep and pediatric bipolar disorder.

STUDY OBJECTIVE: To determine, based on a large community sample, the prevalence and associated sleep characteristics of children with a bipolar mood disturbance behavioral profile. METHODS: Participants who fit the pediatric bipolar disorder profile as derived from the Child Behavior Checklist were matched to control participants for age, sex, ethnicity, parentally reported attention-deficit/hyperactivity disorder, psychotropic medication usage, and apnea-hypopnea indexes. Paired comparisons were made between the groups to examine differences on polysomnographic data and parentally reported sleep characteristics. RESULTS: Thirteen (approximately 3%) of 438 participants fit the pediatric bipolar disorder profile. These children demonstrated significant sleep-continuity disturbances with poorer sleep efficiency and more awakenings after sleep onset, less rapid eye movement sleep, and longer periods of slow-wave sleep than their matched counterparts during overnight polysomnography. In addition, responses to a parental-report questionnaire about child sleep behavior suggest these children have significant sleep problems, including more difficulty initiating sleep, restless sleep, nightmares, and morning headaches relative to the control group. CONCLUSIONS: Children with a pediatric bipolar disorder profile display consistent quantitative differences in sleep relative to matched controls. Prevalence rates of pediatric bipolar disorder, as assessed by the Child Behavior Checklist, are consistent with those found in the adult bipolar population.

Aggression↗

PubMed2006

The time structure of the cyclic alternating pattern during sleep.

STUDY OBJECTIVES: To analyze the intervals between A phases of the cyclic alternating pattern (CAP) and to describe their time structure. This might represent an additional aspect to be studied in sleep pathologies that are accompanied by CAP changes. METHODS: Sleep stages and CAP A phases were identified in polysomnographic night recordings of normal adults and children. Intervals between consecutive CAP A phases were measured, counted, and used to draw individual normalized distribution graphs. The intervals during light sleep (stages 1 and 2) were analyzed separately from those occurring during slow-wave sleep (SWS). Subsequently, we performed a Markovian analysis of intervals, in order to describe in detail their time structure. SETTING: N/A. PARTICIPANTS: Twenty-four adults and 28 children. MEASUREMENTS AND RESULTS: In adults, a preponderance of intervals shorter than 60 seconds during SWS was found; light sleep showed a higher number of intervals longer than 60 seconds. A less clear-cut difference between stages was found in children, who showed a shift of the peak in their SWS histogram toward intervals shorter than in adults. Interval sequences were not determined by a random process in both groups. The Markovian analysis showed statistically significant lower values of entropy and higher values of time dependency, mostly in adults during SWS. CONCLUSIONS: The different CAP components of sleep occur in a non-random ordered fashion, and their time structure is characterized by first-order relationships. SIGNIFICANCE: We postulate that CAP components are the expression of a timely ordered process that exhibits specific sleep stage-related features and undergoes age-related modifications.

Child↗

PubMed2006

Leigh syndrome: anesthetic management in complicated endoscopic procedures.

BACKGROUND: Leigh's syndrome, a disorder of infancy and childhood, is characterized by gray matter degeneration and focal brainstem necrosis. It presents with special clinical features such as developmental delay, nervous system dysfunction, respiratory abnormalities, and hypertrophic cardiomyopathy that can be a real challenge to the anesthesiologist. Anesthesia or sedation has rarely been reported in patients with Leigh disease. We report our experience in sedating five children with Leigh syndrome in seven procedures undertaken in the endoscopy suite (outside the operating room). METHODS: Five children with Leigh disease, three girls and two boys, have been referred to us for percutaneous endoscopic gastrostomy (PEG) insertion and or replacement (a total of seven procedures). The average age was 2.6 years with a range of 4 months to 6 years. Informed consent was obtained from the patient's parents or guardian. An anesthesia machine, scavenging system, O(2) source and routine monitoring were available. Sedation was accomplished with propofol intravenous (i.v.) (0.5-1 mg x kg(-1)) maintained with a propofol infusion (50-100 microg x kg(-1) x min(-1)). The spontaneously breathing patients received oxygen through an oxygen facemask during the procedure and afterwards recovery was managed in the gastroenterology unit. RESULTS: All the children underwent the procedure without complications. One patient developed transient desaturation (SpO(2) 80%) for a few seconds. Body temperature, heart rate, arterial blood pressure, O(2) saturation and endtidal CO(2) were stable during the endoscopies. No special post-procedure management was required; the patients woke up at the end of the endoscopy and were able to drink and eat as usual. CONCLUSIONS: This rare mitochondrial disease presents unique management problems to the anesthesiologist when using general anesthesia. Our patients were managed appropriately before endoscopy and underwent the procedure under deep sedation. No complications occurred. We concluded that deep sedation in the endoscopy suite was safe in this small series of patients with this rare disease.

Anesthetics, Intravenous↗

PubMed2006

Neurocognitive dysfunction in children with sleep disorders.

It is well known that adults with sleep disturbances frequently exhibit a wide range of neurocognitive decrements, and that these deficits are potentially reversible with effective treatment. However, the consequences of respiratory sleep disturbances on neurocognitive function in children have only recently been evaluated, and suggest a strong causal association between the episodic hypoxia and sleep fragmentation that characterize the disease and the emergence of reduced memory, attention and intelligence as well as a link to problematic and hyperactive behaviours and mood disturbances. This article takes a critical look at the current literature on these issues, reviews the major findings and discusses such findings in conjunction with those derived from pertinent animal models.

Animals↗

PubMed2006

Serum proteomic patterns associated with sleep-disordered breathing in children.

Obstructive sleep apnea (OSA) is a major public health problem affecting approximately 2% to 3% of children. However, snoring, the cardinal symptom of OSA, affects at least 5-fold more children, such that evaluation by overnight polysomnography (ONP) is required for the diagnosis. ONP is laborious, expensive, and relatively unavailable to children. Proteomic mass spectrometry coupled with bioinformatic tools provide valuable means for discovery of new biomarkers in serum for a variety of human disorders. The possibility exists that snoring children with and without OSA may exhibit different protein expression profiles in serum that could be useful in the development of novel diagnostic tools for this condition. The proteomic patterns of 20 children with OSA and of 20 children with habitual primary snoring but no evidence of OSA (HS) were evaluated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Linear discriminative analysis identified three differentially regulated proteins with molecular masses of 5896, 3306, 6068 Da that were capable of diagnosing OSA with 93% sensitivity and 90% specificity. Thus, the proteomic signatures of sera from children with OSA differ from those of HS who do not fulfill the current criteria for treatment. Identification and sequencing of those differentially expressed proteins discovered through proteomic strategies may lead to future development of serum-based diagnostic tests for OSA in snoring children.

Adolescent↗

PubMed2006

Plasma adhesion molecules in children with sleep-disordered breathing.

STUDY OBJECTIVES: To determine whether childhood sleep-disordered breathing (SDB) is associated with elevated levels of plasma adhesion molecules. DESIGN: Prospective, observational study. SETTING: Sleep Medicine Center of Kosair Children's Hospital. PARTICIPANTS: Thirty-nine children with SDB (apnea-hypopnea index [AHI] > 5/h), 47 children with mild SDB (AHI 1 to 5/h), and 42 healthy control subjects (AHI < 1/h). MEASUREMENTS AND RESULTS: One hundred twenty-eight children underwent a standard polysomnographic assessment with a blood draw the following morning. Plasma levels of CRP and the adhesion molecules intercellular adhesion molecule (ICAM)-1 and P-selectin were measured. No differences were observed in ICAM-1 levels among the groups; however, obese children had higher ICAM-1 levels than nonobese children (425.0 +/- 123.0 ng/mL vs 375.6 +/- 107.1 ng/mL, p = 0.04) [mean +/- SD]. P-selectin levels were significantly higher in the SDB group (84.0 +/- 52.2 ng/mL) and the mild SDB group (89.3 +/- 49.9 ng/mL) when compared to control subjects (49.5 +/- 22.3 ng/mL; p < 0.001 for both groups). Furthermore, P-selectin correlated with AHI (r = 0.32, p < 0.001), respiratory arousal index (r = 0.27, p = 0.002), and nadir of oxygen saturation as measured by pulse oximetry (r = - 0.19, p = 0.038). Plasma CRP levels were found to correlate with P-selectin even after controlling for BMI (r = 0.20, p = 0.05). No correlations were found between CRP and ICAM-1. CONCLUSIONS: Children with SDB have plasma elevations of P-selectin, a marker of platelet activation, lending support to the premise that inflammatory processes are elicited by SDB in children, and may contribute to accelerated risk for cardiovascular morbidity. In contrast, elevations in ICAM-1 are primarily associated with obesity rather than SDB.

Biomarkers↗

PubMed2006

Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome.

BACKGROUND: Upper airway inflammation is now recognized in adults with obstructive sleep apnea (OSA) syndrome. However, the role played by eicosanoids such as leukotrienes and prostaglandins is unclear. OBJECTIVE: To investigate whether eicosanoids are measurable in exhaled breath condensate (EBC), and to determine whether differences in these inflammatory mediators emerge among children with and without sleep-disordered breathing (SDB). METHODS: EBC was collected from 50 consecutive snoring children undergoing overnight polysomnography for suspected SDB, and from 12 nonsnoring control subjects. Prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and cysteinyl leukotrienes (cys-LTs: leukotriene C4 [LTC4]/leukotriene D4 [LTD4]/leukotriene E4 [LTE4]) EBC levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: LTB4 levels were elevated in children with an apnea-hypopnea index (AHI) > 5/h (SDB; 97.6 +/- 6.3 pg/mL) compared to children with an AHI < 5/h (mild SDB; 66.4 +/- 19.1 pg/mL; p < 0.01) and control subjects (27.8 +/- 3.7 pg/mL; p < 0.01). Similarly, cys-LT (LTC4/LTD4/LTE4) concentrations were also increased in SDB (45.1 +/- 10.6 pg/mL in SDB vs 27.6 +/- 8.3 pg/mL in mild SDB, and 15.7 +/- 7.6 pg/mL in control subjects; p < 0.01). In contrast, PGE2 concentrations were similar among the three groups. CONCLUSIONS: Inflammatory mediators such as leukotrienes and prostaglandins can be readily quantified in EBC collected from the upper airway of children. Disease severity-dependent increases in leukotriene concentrations (LTB4 and LTC4/LTD4/LTE4) emerge among children and may serve as a noninvasive tool in the clinical assessment of these children.

Adolescent↗

PubMed2006

Intranasal steroids and oral leukotriene modifier therapy in residual sleep-disordered breathing after tonsillectomy and adenoidectomy in children.

OBJECTIVE: Tonsillectomy and adenoidectomy (T&A) is the primary therapeutic approach for sleep-disordered breathing (SDB) in children. However, residual mild SDB will be found in more than one third of these patients after T&A. We hypothesized that combined therapy with the leukotriene receptor antagonist montelukast and intranasal budesonide would result in normalization of residual SDB after T&A. METHODS: During the period of October 2002 to February 2005, children who underwent T&A for SDB underwent a routine postoperative (second) overnight polysomnographic evaluation (PSG) 10 to 14 weeks after T&A surgery. In children with residual apnea hypopnea index (AHI) >1 and <5/hour of total sleep time (TST), treatment with montelukast and intranasal budesonide aqueous solution was administered for a period of 12 weeks (M/B group), at which time a third PSG was performed. Children who had residual SDB and did not receive M/B therapy from their treating physicians were recruited as control subjects. RESULTS: Twenty-two children received M/B, and 14 children served as control subjects. Mean age, gender distribution, ethnicity, and BMI were similar in the 2 treatment groups. The mean AHI at the second PSG was 3.9 +/- 1.2/hour of TST and 3.6 +/- 1.4/hour of TST in M/B-treated and control patients, respectively. Similar nadir arterial oxygen saturation (87.3 +/- 1.2%) and respiratory arousal index (4.6 +/- 0.7/hour of TST) were recorded for both groups. However, the M/B group demonstrated significant improvements in AHI (0.3 +/- 0.3/hour of TST), in nadir arterial oxygen saturation (92.5 +/- 3.0%), and in respiratory arousal index (0.8 +/- 0.7/hour of TST) on the third PSG, whereas no significant changes occurred over time in control subjects. CONCLUSIONS: Combined anti-inflammatory therapy that consists of oral montelukast and intranasal budesonide effectively improves and/or normalizes respiratory and sleep disturbances in children with residual SDB after T&A.

Acetates↗

PubMed2006

Polysomnographic characteristics in normal preschool and early school-aged children.

OBJECTIVE: The objective of this study was to describe overnight polysomnographic measures in normal children aged 3 to 7 years. We conducted a retrospective analysis of normal polysomnographic evaluations from participants in 2 large community-based studies of sleep-disordered breathing among preschoolers and early school-aged children at Kosair Children's Hospital Sleep Medicine Research Center at the University of Louisville. Participants included 542 healthy children with ages ranging from 3.2 to 8.6 years. RESULTS: Subjects were excluded from analysis if they had documented snoring during polysomnography, an obstructive apnea-hypopnea index of > or =1.0, or a periodic leg-movement index of > or =5.0. Because the greatest differences in polysomnography occurred between ages 5 and 6 years, analyses were performed for children 3 to 5 years and for ages > or =6. Sleep cyclicity was distinct between age groups, with both showing an initial brief rapid-eye-movement period, which lengthened across the night, but only the older group showing a decrease in cycle length across the night. Average obstructive apnea indices were 0.03 per hour of total sleep time (TST) for 3- to 5-year-old children and 0.05 per hour of TST for > or =6-year-old children, whereas central apnea indices were 0.82 and 0.45 per hour of TST, respectively. Older children spent a greater percentage of sleep time supine, and the apnea-hypopnea index differed according to body position. Twenty percent of all subjects had end tidal carbon dioxide values of >45 mm Hg, and 2.2% had recorded values >50 mm Hg during > or =50% TST. High variance was present on all measures. CONCLUSIONS: Developmental changes occur in several polysomnographic measures among normal children from 3 to 7 years of age, particularly during transition from preschool to early school age. Our findings in a large number of healthy community children comprise the most extensive compilation of normative reference values for laboratory-based pediatric polysomnography to date.

Arousal↗

PubMed2006

Snore-associated sleep fragmentation in infancy: mental development effects and contribution of secondhand cigarette smoke exposure.

OBJECTIVE: The link between sleep-disordered breathing and neurocognitive functioning in preschool and school-aged children now has been established clearly. Within these age groups, isolated studies have examined the potential effect of snoring without gas exchange abnormalities on aspects of cognitive competence. The goal of the study was to test the potential association between snoring and decrements in developmental performance among infants. METHODS: Thirty-five healthy community infants (8.2 +/- 0.4 months) were administered the Bayley Scales of Infant Development, including the Mental Development Index (MDI), after standard, overnight research polysomnography. RESULTS: The apnea-hypopnea index for all infants was 0. Respiratory arousal index was significantly correlated with MDI. Snoring-associated arousals accounted exclusively for this relationship; spontaneous arousals and those that were associated with central apnea and oxyhemoglobin desaturation episodes (> or =4%) were not significantly correlated with MDI. Living in a smoking household was not significantly associated with the presence of objectively recorded snoring but was associated with an increase in arousal frequency in snoring infants. CONCLUSIONS: Infants with lower scores on a standardized mental development assessment had higher snoring-arousal indices. Because neither apnea nor hypopnea was present, these findings constitute additional evidence that snoring is not just an innocent noise during sleep in infants but may in fact represent the lower end of the disease spectrum associated with sleep-disordered breathing. Secondhand exposure to cigarette smoke may increase the deleterious effects of infant snoring.

Arousal↗

PubMed2006

NREM sleep instability is reduced in children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: To evaluate non-rapid eye movement sleep instability (NREM), as measured by the cyclic alternating pattern (CAP), in a cohort of children with attention-deficit/hyperactivity disorder (ADHD) and normal controls. DESIGN: Prospective study. SETTINGS: Sleep laboratory. PARTICIPANTS: Twenty consecutive outpatients with ADHD (18 boys and 2 girls; age range 6-13 years, mean age 9.3 years) and 20 normal children matched for age and socioeconomic status underwent polysomnographic recordings for 2 consecutive nights in a standard laboratory setting. Sleep was visually scored for sleep macrostructure and CAP, according to standard criteria. MEASUREMENTS AND RESULTS: Children with ADHD showed significantly reduced sleep duration and increased rate of stage shifts. All children with ADHD had an apnea-hypopnea index less than 1. Those with ADHD presented lower total CAP rates and lower CAP rates during sleep stage 2 than did normal controls. Moreover, in children with ADHD, we found a lower number of CAP sequences and a reduced total A1 index, mainly in light sleep (sleep stages 1 and 2). We did not find differences in A subtype percentages, but there was a longer duration of A1 subtypes in children with ADHD. CONCLUSIONS: Children with ADHD showed a lower CAP rate and a lower number of CAP sequences; this supports the hypothesis of the existence of a hypoarousal state in these patients.

Adolescent↗

PubMed2005

Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice.

Adult neural progenitor cells (NPCs) are an attractive source for functional replacement in neurodegenerative diseases and traumatic injury to the central nervous system (CNS). It has been shown that transplantation of neural stem cells or NPCs into the lesioned region partially restores CNS function. However, the capacity of endogenous NPCs in replacement of neuronal cell loss and functional recovery of spinal cord injury (SCI) is apparently poor. Furthermore, the temporal and spatial response of endogenous adult NPCs to SCI remains largely undefined. To this end, we have analyzed the early organization, distribution, and potential function of NPCs in response to SCI, using nestin enhancer (promoter) controlled LacZ reporter transgenic mice. We showed that there was an increase of NPC proliferation, migration, and neurogenesis in adult spinal cord after traumatic compression SCI. The proliferation of NPCs detected by 5-bromodeoxyuridine incorporation and LacZ staining was restricted to the ependymal zone (EZ) of the central canal. During acute SCI, NPCs in the EZ of the central canal migrated vigorously toward the dorsal direction, where the compression lesion is generated. The optimal NPC migration occurred in the adjacent region close to the epicenter. More significantly, there was an increased de novo neurogenesis from NPCs 24 hours after SCI. The enhanced proliferation, migration, and neurogenesis of (from) endogenous NPCs in the adult spinal cord in response to SCI suggest a potential role for NPCs in attempting to restore SCI-mediated neuronal dysfunction.

Animals↗

PubMed2005

Developmental plasticity of respiratory control following intermittent hypoxia.

During development, windows of increased vulnerability to noxious stimulus occur. These critical periods of maturation represent times at which the maturing animal is uniquely susceptible to external perturbations that may alter the ultimate configuration of neural networks and their associated function(s), thereby inducing persistent (mal)adaptive changes. In contrast, when comparable perturbations are applied to adult animals the associated adaptive changes do not typically persist. This principle has been demonstrated in models of respiratory plasticity in developing mammals including exposure to sustained hypoxia, hyperoxia, and pharmacological agents. Recently, intermittent hypoxia (IH) during development has also been implicated as a potent inducer of respiratory plasticity. Altered ventilatory patterning induced by IH is distinct from other stimuli and elicits markedly different responses in the developing mammal as compared to the adult. Furthermore, adaptations to acute IH (AIH) exposure may involve mechanisms that differ from those invoked by chronic IH exposure (CIH). Thus, critical examination of IH exposure paradigms is also an important consideration. Greater understanding of IH-induced ventilatory plasticity, particularly in the developing animal, will undoubtedly increase our understanding of IH related diseases such as sleep disordered breathing, and perhaps provide future directions for intervention strategies.

Animals↗

PubMed2005

Bradykinin B2 receptors mediate pulmonary sympathetic afferents induced reflexes in rabbits.

Endogenous bradykinin (BK) is an established mediator of pulmonary inflammation, yet its role in lung disease is unclear. In the rabbit, injecting BK into the lung parenchyma elicits reflex hyperpnea, tachypnea, hypotension, and bradycardia by stimulating pulmonary sympathetic afferents. To further explore bradykinin effects, breathing pattern (phrenic nerve and abdominal muscle activities) and hemodynamics (blood pressure and heart rate) were examined in anesthetized, open-chest, and mechanically ventilated rabbits. Three receptor agonists [bradykinin, selective B(1) (des-Arg(9)-BK), and selective B(2) (Tyr(8)-BK)], as well as three B(2) receptor antagonists, B6029 (N alpha-Adamantaneacetyl)-Bradykinin, B(1)650 (D-Arg-[Hyp(3), Thi(5,8), D-Phe(7)]-Bradykinin, or Hoe-140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)] bradykinin), were used to identify the responsible receptor subtype. In both intact and vagotomized rabbits, injecting BK or a selective B(2) agonist into the lung elicited similar cardiopulmonary responses. These reflex responses were greatly attenuated or blocked by pre-injecting B(2) antagonists into the right atrium or into the lung parenchyma. In contrast, the B(1) agonist elicited fewer cardiopulmonary effects in intact rabbits and had no effect in vagotomized rabbits. We conclude that BK stimulates pulmonary sympathetic afferents [Soukhova, G., Wang, Y., Ahmed, M., Walker, J., Yu, J., 2003. Bradykinin stimulates respiratory drive by activating pulmonary sympathetic afferents in the rabbit. J. Appl. Physiol. 95, 241-249.; Wang, Y., Soukhova, G., Proctor, M., Walker, J., Yu, J., 2003. Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit. J. Appl. Physiol. 95, 233-240.], eliciting a characteristic cardiopulmonary reflex via B(2) receptors.

Adamantane↗