Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Monin, Philippe; Aranda, J. V.; Bansal, Reeta; Trippenbach, Teresa

doi:10.1159/000014156

Cited by 5 publications

(4 citation statements)

References 46 publications

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“…This administration method may supress not only the medulla oblongata but also higher brainstem and other brain regions. It was reported that supramedullary brain regions are involved in hypoxic ventilatory depression (Monin et al 1999) and send inhibitory signals to the medulla oblongata during hypoxic exposure due to release and local accumulation of inhibitory neurotransmitters (GABA, dopamine, adenosine). Under these conditions, injection of GABA into the lateral ventricle may suppress hypoxia-induced ventilatory inhibitory mechanisms of the midbrain and pons; this suppression may reverse hypoxic ventilatory depression and even increase ventilation during hypoxia.…”

Section: Discussionmentioning

confidence: 99%

“…3). Therefore, the increased ventilation following exogenous ICV GABA administration may be attributed either to GABA-evoked block of the cerebellar inhibitory input during hypoxia (Monin et al 1999) or to the releasing of the glutamate by the effect of both exogenous GABA and hypoxia, independent of the stimulation of peripheral chemoreceptor afferents. On the other hand, the response of BP was found to be significantly decreased, as expected.…”

Section: Discussionmentioning

confidence: 99%

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The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Yelmen

2004

Tohoku J. Exp. Med.

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Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed by a decrease in ventilation. Hypoxia causes changes in brain neurotransmitters depending on its severity and durations. The purpose of this study was to investigate the role of gamma-aminobutyric acid (GABA) and glutamate for hypoxic ventilatory response in rabbits. The experiments were performed in peripheral chemoreceptors intact and denervated rabbits anesthetized with Na-pentobarbitate. For intracerebroventricular (ICV) injections of reagents in each animal, cannula was placed in left lateral cerebral ventricle by stereotaxic method. After ICV injection of GABA (0.48 mg/kg), air breathing in both groups caused a depression of respiratory activity. On the other hand, after ICV injection of GABA, breathing of hypoxic gas mixture (8% O 2 -92% N 2 ) in both groups produced the hypoxic hyperventilation. After ICV injection of GABA, blockade of GABA A receptors with bicuculline (0.2 mg/kg) did not prevent the hypoxic hyperventilation. In contrast, after ICV GABA injection, blockade of glutamate NMDA receptors with MK-801 (0.09 mg/kg) completely abolished the hypoxic hyperventilation observed while the animals were breathing hypoxic gas mixture. Our findings suggest that ICV injection of GABA causes respiratory depression in normoxic conditions, and that it increases ventilation in hypoxic conditions with or without peripheral chemoreceptor impulses by increasing glutamate.GABA; hypoxia; control of breathing; bicuculline; MK-801

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Yelmen

2004

Tohoku J. Exp. Med.

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“…The following pharmaceutics agents can be classified in this group: (1) beta-adrenomimetics [82][83][84]; (2) gutiminebased [82] and (3) GABA-and taurin-based agents [85][86][87][88][89][90], L-carnitine [91].…”

Section: Paas That Decrease Cellular Metabolismmentioning

confidence: 99%

Remediation of Cellular Hypoxic Damage by Pharmacological Agents

Minko¹,

Wang²,

Pozharov³

2005

CPD

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Many known pathological conditions lead to decreases in oxygen supply to various cells. When secondary cellular hypoxia becomes severe, it causes additional cellular damage, aggravating the primary disorder and leading to cell death. Therefore, remediation of secondary hypoxic damage should significantly increase the efficacy of the treatment of primary disease and prevent extensive cellular damage. Analysis of the literature and our experimental data show that the main mechanisms of secondary hypoxic cellular damage include lactate acidosis (lactic acidosis), the boost in free radical processes and the activation of apoptosis and necrosis. These factors result in damage to cellular membranes which in turn further limits oxygen supply leading to augmented hypoxic cellular damage. Therefore, to effectively break this vicious cycle of cellular hypoxia, antihypoxic therapy should simultaneously: (1) mitigate existing cellular hypoxic damage; (2) increase cellular ability to utilize available oxygen; (3) amplify the power of cellular antioxidant defense and (4) prevent hypoxic activation of apoptosis and necrosis. It is clear that such complex task cannot be fulfilled by a single pharmacological agent. Therefore, a complex multi component antihypoxic drug delivery system should be designed to address all the four desiderata indicated above. This review will examine existing pharmaceutical antihypoxic preparations and evaluate the new methods for the pharmacological remediation of cellular hypoxic damage and propose future directions for the design of the needed drug delivery systems.

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“…Cerebellar outflow processes, consisting of GABAergic neurons, affect a range of somatomotor, autonomic motor (Lutherer et al, 1983; Zhu et al, 2006) and cognitive functions (Schmahmann et al, 2007; Tavano et al, 2007), and serve chemosensing (Xu and Frazier, 1997) and coordination of breathing (Monin et al, 1999) roles. Extensive evidence indicates that adult cerebellar neurons, including Purkinje cells, are predominantly GABAergic (Takayama, 2005) and are inhibitory in function.…”

Section: Introductionmentioning

confidence: 99%

Perinatal intermittent hypoxia alters γ‐aminobutyric acid: a receptor levels in rat cerebellum

Pae¹,

Yoon²,

Ahuja³

et al. 2011

Intl J of Devlp Neuroscience

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Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits.

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Effect of Increased Brain GABA Concentrations on Breathing in Unanesthetized Newborn Rabbits

Cited by 5 publications

References 46 publications

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

Remediation of Cellular Hypoxic Damage by Pharmacological Agents

Perinatal intermittent hypoxia alters γ‐aminobutyric acid: a receptor levels in rat cerebellum

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