Glutamate antagonism fails to reverse mitochondrial dysfunction in late phase of experimental neonatal asphyxia in rats

Reddy, Nagannathahalli Ranga; Krishnamurthy, Sairam; Chourasia, T.K.; Kumar, Ashok; Joy, K.P.

doi:10.1016/j.neuint.2011.01.021

Cited by 7 publications

(4 citation statements)

References 88 publications

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“…* P<0.05 compared to control [two tailed unpaired Student-t test] complex-II to anoxia. Previous experimental studies have shown compromised complex-II after anoxic exposure (Bolaños et al 1998;Reddy et al 2011). RCR is the ratio of state III to state IV respiration and is a measure of mitochondrial integrity (Gilmer et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, mitochondria may be an important target for the progression of primary anoxic injury into secondary injury. Therefore, energy deficiency due to mitochondrial dysfunction plays a key role in post anoxic brain damage in newborns (Bolaños et al 1998;Reddy et al 2011;Rosenberg et al 1989). …”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we have used the non-invasive two episodic model of anoxia in neonatal rats to study the role of mitochondrial bioenergetics in asphyxia (Reddy et al 2011). This method is better optimized than other similar anoxic models as it uses two subsequent episodes of anoxia rather than a single prolonged episode.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats

Samaiya

Krishnamurthy

2015

J Bioenerg Biomembr

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Neonatal anoxia at the time of birth can lead to mitochondrial dysfunction and further neurodevelopmental abnormalities. The present study investigated the mitochondrial bioenergetics and associated sensorimotor changes in the anoxic neonatal rats. Rat pups after 30 h to birth (2 days) were subjected to anoxia of two episodes (10 min in each) at a time interval of 24 h by passing 100 % N2 into an enclosed chamber. Brain mitochondrial respiration was measured using clark type oxygen electrode. A significant decrease in brain respiratory control ratio (RCR; State III/IV respiration) at all-time points, complex I (24 h) and complex II (30 min, 6 and 24 h) enzyme activities indicated loss of mitochondrial integrity and function A significant increase in levels of nitric oxide was observed after second anoxic episode at all-time points. A significant change in sensorimotor activity in terms of increased reflex latency was observed 24 h after second episode in this model, which is an indication of loss of subcortical maturation. All the above changes were observed after second but not after the first anoxic exposure. Therefore, this anoxic model shows significant changes in mitochondrial bioenergetics, nitric oxide levels and sensorimotor effects after second episode of anoxia. This model may be helpful to evaluate mitochondrial targeted pharmacological intervention for the treatment of anoxia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats

Samaiya

Krishnamurthy

2015

J Bioenerg Biomembr

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“…An estimated 23% of worldwide deaths per year during the first four weeks of life are due to NA and the consequences of hypoxic-ischemic insults affect 2-4 newborns (NB) per 1,000 live births. Among premature babies, the death rate due to NA increases to about 60% ( 7 ) and can cause necrotizing enterocolitis (NEC) in 6% of them ( 8 - 10 ).…”

Section: Introductionmentioning

confidence: 99%

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

Figueira

Gonçalves

Simões

et al. 2016

Braz J Med Biol Res

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Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

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Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses

et al. 2018

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Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses' brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.

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Glutamate antagonism fails to reverse mitochondrial dysfunction in late phase of experimental neonatal asphyxia in rats

Cited by 7 publications

References 88 publications

Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats

Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses

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