Neuronal Death in Newborn Striatum after Hypoxia-Ischemia Is Necrosis and Evolves with Oxidative Stress

Martin, Lee J.; Brambrink, Ansgar M.; Price, Angie; Kaiser, Adeel; Agnew, Dawn Mueller; Ichord, Rebecca; Traystman, Richard J.

doi:10.1006/nbdi.2000.0282

Cited by 126 publications

(157 citation statements)

References 72 publications

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“…The disturbance in this balance damages the lipids, proteins, and DNA resulting in their oxidation and causing cell death by necrosis or apoptosis. It is well documented that hypoxia induces oxidative stress that plays a pivotal role in damaging the neurons in the adult and developing neural tissues [116][117][118][119][120]. ROS has been reported to be involved in signaling RGC death by acting as a second messenger and/or modulating protein function in conditions such as glaucoma [121][122][123] and ischemic injuries of the retina [107,124].…”

Section: Hypoxia and Oxidative Stressmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries

Kaur¹,

Rathnasamy²,

Foulds³

et al. 2015

J Neurol Exp Neurosci

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Loss of retinal ganglion cells (RGCs) occurs in retinal degenerative diseases, such as glaucoma, age-related macular degeneration, diabetic retinopathy, central retinal artery occlusion and ischemic central retinal vein thrombosis in adults and in retinopathy of prematurity in infants. A critical role of hypoxia, which underlies most of the above disorders, has been reported in causing RGC death. Disruption of blood-retinal barrier (BRB) occurs due to increased production of vascular endothelial growth factor and nitric oxide in response to hypoxia resulting in extravasation of serum derived substances and retinal edema and this may be one of important factors mediating RGC death. Activation of microglial cells in response to hypoxia and subsequent increased release of proinflammatory cytokines by them such as tumor-necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) target the TNF-receptor 1 and IL-receptor 1 on RGCs. Excess release of glutamate in retinal tissue under hypoxia activates the ionotropic glutamate receptors causing excitotoxicity through increased influx of calcium into the RGCs. Increased production of TNF-α, IL-1β and enhanced intracellular calcium results in RGC death through activating several pathways such as caspase signaling, mitochondrial dysfunction and oxidative stress. In our investigations, melatonin, an antioxidant, was shown to reduce RGC death in the adult and neonatal hypoxic retina, through suppression of TNF-α, IL-1β and glutamate levels as well as oxidative stress. Moreover, the function and structure of BRB was well preserved in these animals along with reduction in retinal edema. In view of our observations, we suggest that melatonin could be considered as a therapeutic agent to reduce RGC death in various retinal pathologies, in addition to other potential drugs/molecules of therapeutic interest that could render protection to RGCs. However, future in-depth research on the effects of melatonin on the retina under hypoxic conditions needs to be undertaken to explore its full potential in preventing/ameliorating RGC death. Factors Mediating RGC DeathSeveral factors induced or upregulated by hypoxia may be involved in causing RGC death. These factors include, among others, disruption of the blood-retinal barrier, activation of microglial cells and the accompanying enhanced release of inflammatory cytokines and excess release and accumulation of glutamate in the retinal tissues. Hypoxia and the blood-retinal barrierThe BRB regulates the passage of molecules from blood into the retina [11,12]. It consists of an inner BRB formed by the tight junctions (TJ) between capillary endothelial cells and an outer barrier formed by TJ between retinal pigment epithelial cells [12][13][14][15][16]. The TJ are made up of transmembrane proteins such as occludin, claudin-5 and cytoplasmic proteins such as zona occludens (ZO)-1 that are structurally and functionally important for maintaining the integrity of the BRB. The proper functioning of the inner BRB also requires the collective co...

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Section: Hypoxia and Oxidative Stressmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries

Kaur¹,

Rathnasamy²,

Foulds³

et al. 2015

J Neurol Exp Neurosci

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“…Then, just after birth, the newborn child is exposed to oxidative stress because of acute reoxygenation when breathing begins. It is known that acute reoxygenation after hypoxia may produce an extensive oxidative damage through the same mechanisms that also produce ischemia-reperfusion injury (IRI) and asphyxia-reventilation injury (Martin et al, 2000). Thus, returning to Hamlet's metaphor, we may add that humans &&su+er the slings and arrows of outrageous fortune'' and have &&a sea of troubles'' from the very beginning of their lives.…”

Section: Reliability Theory Of Aging For Highly Redundant Systems Repmentioning

confidence: 99%

“…This standard assumption may be justi"ed for technical devices manufactured from pre-tested components, but it is not justi"ed for living organisms, presumably replete with defects, for the reasons described earlier [see previous discussion of relevant publications (Dobzhansky, 1962;Finger et al, 1988;Mo!ett et al, 1993;Gri$ths et al, 1996;Handyside & Delhanty, 1997;McLaren, 1998;Martin et al, 2000) and Figs 1 and 2]. It is therefore worthwhile to examine another particular case of the model in which initially functional elements occur very rarely with a low probability q.…”

Section: Reliability Theory Of Aging For Highly Redundant Systems Repmentioning

confidence: 99%

Reliability Theory of Aging and Longevity

Gavrilov

Gavrilova

2005

Handbook of the Biology of Aging

167

262

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Reliability theory is a general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems that are entirely composed of non-aging elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Aging, therefore, is a direct consequence of systems redundancy. Reliability theory also predicts the late-life mortality deceleration with subsequent leveling-o!, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial -aws (defects) in newly formed systems. It also explains why organisms &&prefer'' to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Theoretical conditions are speci"ed when organisms die according to the Weibull law: organisms should be relatively free of initial #aws and defects. The theory makes it possible to "nd a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative di!erences in mortality rates of compared populations (within a given species) vanish with age, and mortality convergence is observed due to the exhaustion of initial di!erences in redundancy levels. Overall, reliability theory has an amazing predictive and explanatory power with a few, very general and realistic assumptions. Therefore, reliability theory seems to be a promising approach for developing a comprehensive theory of aging and longevity integrating mathematical methods with speci"c biological knowledge. Academic Press

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“…Corpus striatum becomes selectively vulnerable in the hypoxic term piglet model. In a piglet model of hypoxic-ischemic brain injury in newborns, striatal neuron necrosis evolves rapidly (33). We have investigated changes in corpus striatum in a global hypoxia piglet model, imitating birth asphyxia, as in several of our earlier studies (34,35).…”

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confidence: 99%

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

Munkeby

Børke

Björnland³

et al. 2004

Pediatr Res

120

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Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O 2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O 2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O 2 compared with 21% O 2 . Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p ϭ 0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O 2 (p ϭ 0.003) and 100% O 2 (p ϭ 0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O 2 as compared with 21% O 2 (p Ͻ 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O 2 were considerably reduced compared with both baseline (p ϭ 0.001) and piglets that were resuscitated with 21% O 2 (p ϭ 0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Traditionally, asphyxiated newborn infants have been resuscitated using 100% oxygen in the delivery room (1). However, clinical trials have shown that room air is as efficient as pure oxygen in securing the survival of asphyxiated newborn infants (2-5). Therefore there is an ongoing debate whether to use ambient air or 100% O 2 in neonatal resuscitation (6 -9).Hyperoxia followed by reoxygenation is thought to increase the production of reactive oxygen species and disrupt the antioxidant mechanisms (10). Elevated oxidative stress can directly influence the cell cycle and additionally alter a number of significant cell functions, such as signal transduction, DNA and RNA synthesis, protein synthesis, and enzyme activation (11,12). Furthermore, hypoxic-ischemic injury and reactive oxygen species are found to trigger inflammation in the immature brain (13).Interstitial glycerol is a sensitive and reliable marker of cell damage in experimental cerebral ischemia (14 -16). Degradation of membrane phospholipids is a well-known phenomenon in acute brain injuries and is thought to underlie the disturbance of vital cellular membrane functions.Matrix metalloproteinases (MMPs) are a family of Ͼ20 zinc-and calcium-dependent endopeptidases that are involved in the remodeling of the extracellular matrix (ECM) in a variety of physiologic and pathologic conditions (17

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Neuronal Death in Newborn Striatum after Hypoxia-Ischemia Is Necrosis and Evolves with Oxidative Stress

Cited by 126 publications

References 72 publications

Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries

Cellular and Molecular Mechanisms of Retinal Ganglion Cell Death in Hypoxic-Ischemic Injuries

Reliability Theory of Aging and Longevity

Resuscitation with 100% O2 Increases Cerebral Injury in Hypoxemic Piglets

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