Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses

Crépel, Valérie; Hammond, Constance; Krnjević, K.; Chinestra, Patrick; Ben‐Ari, Yehezkel

doi:10.1152/jn.1993.69.5.1774

Cited by 82 publications

(33 citation statements)

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“…Such long-term OGD is known to cause significant neuronal damage. Quite brief episodes of OGD are usually used to induce long-term potentiation-like events in CA1 pyramidal neurons of acute hippocampal slices [21,22] and are not considered to be destructive. Recently, brief transient periods of OGD (up to 10 min) have been shown to cause rapid ultrastructural changes in synaptic apparatus in hippocampal slice cultures [3], presumably presenting morphological substrate for post-ischemic long-term potentiation [23].…”

Section: Discussionmentioning

confidence: 99%

Morphological and functional changes in rat hippocampal slice cultures after short‐term oxygen‐glucose deprivation

Lushnikova

Воронин

Malyarevskyy

et al. 2004

J Cellular Molecular Medi

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To study effects of short‐term cerebral ischemia, hippocampal slice cultures were subjected to oxygen and glucose deprivation (OGD) followed by a period of normoxic reoxygenation. Propidium iodide staining, and MTT/formazanassay were used to evaluate cell viability and metabolic activity. CA1 pyramidal cells were analyzed at the light‐and electron microscopic levels. Cell damage was found to be insignificant during the first hour after 10 min OGD but profound following 4 h, showing delayed neuronal cell damage caused by short‐term OGD. Our model can be used to characterize the mechanisms of cell damage caused by mild cerebral ischemia. These data might apply to further development of neuroprotective tools for the treatment of brain diseases.

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Section: Discussionmentioning

confidence: 99%

Morphological and functional changes in rat hippocampal slice cultures after short‐term oxygen‐glucose deprivation

Lushnikova

Воронин

Malyarevskyy

et al. 2004

J Cellular Molecular Medi

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“…Mild ischemia causes overactivation associated with unregulated calcium inflow and consequent delayed neuronal death, whereas severe ischemia causes inactivation with transmission failure. 79 Synaptic failure as a result of NMDA receptor inactivation has been shown repeatedly in vitro 80,40 and in vivo, 79 and it has been associated with increased phosphorylation of the receptor. 81,82 However, coexisting damage of presynaptic functions and neuronal damage were not unequivocally refuted in any of the studies examining postsynaptic effects.…”

Section: Evidence Of Postsynaptic Failurementioning

confidence: 99%

Ischemic Cerebral Damage

Hofmeijer¹,

Putten²

2012

Stroke

231

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Abstract-In the human brain, Ϸ30% of the energy is spent on synaptic transmission. Disappearance of synaptic activity is the earliest consequence of cerebral ischemia. The changes of synaptic function are generally assumed to be reversible and persistent damage is associated with membrane failure and neuronal death. However, there is overwhelming experimental evidence of isolated, but persistent, synaptic failure resulting from mild or moderate cerebral ischemia. Early failure results from presynaptic damage with impaired transmitter release. Proposed mechanisms include dysfunction of adenosine triphosphate-dependent calcium channels and a disturbed docking of glutamate-containing vesicles resulting from impaired phosphorylation. We review energy distribution among neuronal functions, focusing on energy usage of synaptic transmission. We summarize the effect of ischemia on neurotransmission and the evidence of long-lasting synaptic failure as a cause of persistent symptoms in patients with cerebral ischemia. Finally, we discuss the implications of synaptic failure in the diagnosis of cerebral ischemia, including the limited sensitivity of diffusion-weighted MRI in those cases in which damage is presumably limited to the synapses. (Stroke. 2012;43:607-615.)Key Words: brain metabolism Ⅲ cerebral ischemia Ⅲ synaptic failure T he human brain is metabolically expensive. Although it represents only 2% of the body weight, it accounts for 20% of oxygen consumption and 25% of glucose utilization. 1,2 Cerebral ischemia is a pathological condition in which blood flow to the brain is insufficient to meet these metabolic demands, causing a loss of neuronal function and viability. Ischemia may be focal if a brain artery is occluded or global, for example, after cardiac arrest.In the 1950s, the concept of perfusion thresholds was introduced. 3 It was shown that functional activity became impaired with moderately reduced perfusion (14 -35 mL/100 g/min), along with electroencephalographic and evoked potential disturbances, whereas loss of ion gradients across the plasma membrane and subsequent cell swelling occur at lower perfusion levels Ϸ4.8 to 8.4 mL/100 g/min (Figure 1). [3][4][5] In focal brain ischemia, the brain tissue that is perfused in the flow range between these 2 levels is now called the penumbra. 6 The penumbra is considered structurally intact and viable, but functionally silent. The dysfunction is, in principle, reversible by restoration of blood flow. However, if oxygen and glucose are not resupplied in time, irreversible damage occurs.Knowledge on the distribution of energy usage among different neuronal activities may contribute to understanding the successive loss of cell function and cell damage in cerebral ischemia. In the human brain, Ϸ30% of the energy is spent on synaptic transmission. 7 Disappearance of synaptic activity is the earliest consequence of cerebral ischemia 8 and failure of synaptic transmission has been proposed to account for electric silence in the penumbra. 3,6,8 -10 The changes of syna...

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“…Previous work has shown that application of a brief OGD to hippocampal slices results in a lasting increase of excitatory synaptic strength, mimicking theta burst-induced LTP and without effects on immediate cell survival (Crepel et al, 1993;Hammond et al, 1994;Hsu and Huang, 1997;Jourdain et al, 2002). This lasting synaptic potentiation was therefore called anoxic LTP.…”

Section: Axo-somatic Inhibitory Synapsesmentioning

confidence: 99%

Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

et al. 2011

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygeneglucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Threedimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatoryeinhibitory balance. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

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Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses

Cited by 82 publications

References 0 publications

Morphological and functional changes in rat hippocampal slice cultures after short‐term oxygen‐glucose deprivation

Morphological and functional changes in rat hippocampal slice cultures after short‐term oxygen‐glucose deprivation

Ischemic Cerebral Damage

Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells

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