Characterization and Developmental Aspects of Anoxia-Induced Gasping in the Rat

Gozal, David; Torres, José E.; Gozal, Yair M.; Nuckton, Thomas J.

doi:10.1159/000244377

Cited by 47 publications

(50 citation statements)

References 25 publications

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“…The gasping variables quantitated included gasp latency, i.e., the period of time from onset of primary apnea and animal immobility to the first gasp, the number and type of gasps, the duration of gasps, and the gasping frequency. In addition, the gasping stage was divided into three major phases (P1-P3) as previously characterized for developing rat pups [26]. In brief, P1 consists of relatively frequent type I gasps (1 2 min -1 ) which display a prominent initial expiratory component followed by inspiratory and expiratory elements ( fig.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Modulates Anoxia-Induced Gasping in the Developing Rat

Gozal

Torres²,

Gozal³

et al. 1998

Neonatology

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Gasping is an important mechanism for survival. Nitric oxide (NO) plays an excitatory role in brainstem regions mediating respiratory responses to hypoxia. We hypothesized that neural structures mediating anoxia-induced gasping would display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures with 100% N₂ in a plethysmograph following administration of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg), a NO precursor, or normal saline. In general, gasp latencies were significantly shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition prolonged gasping duration and reduced gasping frequency at all postnatal ages, although this effect was particularly increased with advancing postnatal age. NADPH-diaphorase staining and Western blots of protein lysates from the lateral tegmental field, the putative neural center underlying gasp generation, revealed progressively increased neuronal NOS abundance with animal maturation. We conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms in neonatal pups. We postulate that higher NO brainstem concentrations may favor early autoresuscitation but be detrimental to overall survival during prolonged asphyxia.

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Section: Discussionmentioning

confidence: 99%

Nitric Oxide Modulates Anoxia-Induced Gasping in the Developing Rat

Gozal

Torres²,

Gozal³

et al. 1998

Neonatology

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“…The duration of hyperpnea, primary apnea, and gasping as well as the gasping frequency were determined manually. The gasping period of animals examined using flow plethysmography was further divided into three phases as described previously (25). The duration and gasping frequency of each phase were calculated manually.…”

Section: Il-1␤ Inhibits Breathing Via Prostaglandinmentioning

confidence: 99%

IL-1β Depresses Respiration and Anoxic Survival via a Prostaglandin-Dependent Pathway in Neonatal Rats

et al. 2003

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IL-1␤ has been proposed to be an important mediator linking infection, apnea, and sudden infant death syndrome. We hypothesized that IL-1␤ acts in this capacity by depressing brainstem respiratory neurons via a prostaglandin-dependent pathway. For studying the effects of IL-1␤ on respiration as well as the mechanism underlying its actions, 7-d-old rats received an initial injection (i.p.) of NaCl or a cyclooxygenase inhibitor (indomethacin, 10 mg/kg) followed by a second injection (i.p.) at 30 min of NaCl, recombinant rat IL-1␤ (10 g/kg), or lipopolysaccharide (LPS; 100 g/kg). Respiration during normoxia and in response to anoxia (100% N 2 ) was examined at 60 min after the second injection using flow and barometric plethysmography. Animals given IL-1␤ breathed more slowly and died more often after anoxia. LPS also reduced the rats' ability to autoresuscitate and survive an anoxic challenge. Indomethacin prevented the depressive effects during normoxia and the adverse effects on survival. For investigating drug-induced changes in central respiratory activity, IL-1␤ (1.0 or 1.25 ng/mL) and prostaglandin E 2 (5 or 20 g/L) was applied to the brainstem-spinal cord preparation of 0-to 4-d-old rats. Whereas IL-1␤ exerted no effect on respiration measured at the C4 ventral root during a 60-min period, prostaglandin E 2 reversibly inhibited respiratory activity. These findings suggest that IL-1␤ does not inhibit respiratory neurons directly but may depress breathing and hypoxic defense via a prostaglandin-mediated mechanism. Abbreviations BBB, blood-brain barrier COX-2, cyclooxygenase-2 f R , respiratory frequency LPS, lipopolysaccharide NTS, nucleus of the solitary tract PGE 2 , prostaglandin E 2 RVLM, rostral ventrolateral medulla Infection, hypoxia, and apnea each have been implicated in the pathogenesis of sudden infant death syndrome, and it has been postulated that the proinflammatory cytokine IL-1␤ may serve as the critical link between them (1, 2). IL-1␤ is released during an acute-phase immune response and subsequently induces multiple effects within the CNS, including the initiation of fever, sleep, and neuropeptide release [for review, see (3)]. Previous studies indicated that this immunomodulator may also alter respiration and autoresuscitation, yet the mechanism underlying such effects must be further elucidated (4 -7). Systemic administration of IL-1␤ has been shown to induce time-and dose-dependent expression of early immediate genes in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), both of which contain neurons important for respiratory control and the latter houses the central pattern generator for breathing (8,9). Because of its size and lipophilic properties, IL-1␤ does not diffuse readily across the blood-brain barrier (BBB) (10). However, IL-1␤ may still communicate with the brain across the BBB via active transport passage, through circumventricular organs, vagal afferent stimulation, and via second messenger induction at the BBB [for review, see (11)].We propose ...

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“…1b) such that the three previously described gasping phases coincided with changes in NO tissue levels ( fig. 1b) [2]. Initial gasping efforts were accompanied by increasing NO tissue levels and were followed by a second phase during which the gasping frequency declined and which was associated with decreases in NO concentrations.…”

Section: Resultsmentioning

confidence: 97%

“…The gasping variables quantitated included gasp latency, i.e., the period of time from onset of primary apnea and animal immobility to the first gasp, the duration Gozal/Torres of gasps, and the gasping frequency as previously described [2]. Gasps were recognized from the plethysmographic recording and confirmed from the observer's notes.…”

Section: Statisticsmentioning

confidence: 99%

“…The latter is then followed within a variable period of time by gasping respiratory efforts which will finally cease, as terminal apnea emerges [1]. In developing rats, a triphasic gasping response occurs in response to anoxia, and such response becomes monophasic at approximately 20 days postnatally [2]. We have previously shown that generation of the initial gasping efforts is critically dependent on activation of N-methyl-D-aspartate (NMDA) glutamate receptors [3].…”

Section: Introductionmentioning

confidence: 99%

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Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

Gozal

Torres²

2001

Neonatology

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Gasping is an important mechanism for survival that appears to be developmentally modulated by the glutamate-nitric oxide (NO) pathway. However, the temporal characteristics of NO brain tissue levels during gasping are unknown. We hypothesized that during anoxia-induced gasping, the gasping frequency would be closely correlated with caudal brainstem tissue NO concentrations in developing rats. Brainstem and cortical tissue NO levels were measured during anoxia using a voltammetric electrode in adult rats and 5-day-old pups during control conditions and following pretreatment with the NMDA receptor antagonist MK-801 (1 mg/kg) or the neuronal NO synthase inhibitor 7-nitro-indazole (7-NI; 100 mg/kg). In young animals, NO tissue levels followed a triphasic trajectory coincident with gasp frequency which was markedly altered by MK-801 and 7-NI, albeit with preservation of gasp frequency-NO tissue level relationships. In adult rats, 40-fold higher NO tissue levels occurred and followed a monophasic trajectory coincident with gasp patterning. In the cortex, monophasic increases in NO levels occurred at all ages. We conclude that anoxia-induced gasping neurogenesis is modulated via NMDA-NO mechanisms in the developing rat. We postulate that higher NO brainstem concentrations may favor early autoresuscitation, but limit anoxic tolerance.

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Characterization and Developmental Aspects of Anoxia-Induced Gasping in the Rat

Cited by 47 publications

References 25 publications

Nitric Oxide Modulates Anoxia-Induced Gasping in the Developing Rat

Nitric Oxide Modulates Anoxia-Induced Gasping in the Developing Rat

IL-1β Depresses Respiration and Anoxic Survival via a Prostaglandin-Dependent Pathway in Neonatal Rats

Brainstem Nitric Oxide Tissue Levels Correlate with Anoxia-Induced Gasping Activity in the Developing Rat

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