‘Ischemic tolerance’ phenomenon found in the brain

Kitagawa, Kazuo; Matsumoto, Masayasu; Tagaya, Masayoshi; Hata, Ryuji; Ueda, Hirokazu; Niinobe, Michio; Handa, Nobuo; Fukunaga, Ryuzo; Kimura, Kazufumi; Mikoshiba, Katsuhiko; Kamada, Takenobu

doi:10.1016/0006-8993(90)90189-i

Cited by 1,026 publications

(559 citation statements)

References 25 publications

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“…It was discovered in the early 1990s (Kitagawa et al, 1990) that exposing the brain to sublethal injury increases its tolerance for subsequent insults (Gidday, 2006). Among the stimuli investigated for induction of tolerance are sublethal ischemia and proinflammatory mediators (Stagliano et al, 1999;Dawson and Dawson, 2000;Dirnagl et al, 2003;Kunz et al, 2007).…”

Section: Nitric Oxide-role In Cerebral Ischemic Preconditioningmentioning

confidence: 99%

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

Terpolilli¹,

Moskowitz

Plesnila³

2012

J Cereb Blood Flow Metab

128

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Some 40 years ago it was recognized by Furchgott and colleagues that the endothelium releases a vasodilator, endothelium-derived relaxing factor (EDRF). Later on, several groups identified EDRF to be a gas, nitric oxide (NO). Since then, NO was identified as one of the most versatile and unique molecules in animal and human biology. Nitric oxide mediates a plethora of physiological functions, for example, maintenance of vascular tone and inflammation. Apart from these physiological functions, NO is also involved in the pathophysiology of various disorders, specifically those in which regulation of blood flow and inflammation has a key role. The aim of the current review is to summarize the role of NO in cerebral ischemia, the most common cause of stroke.

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Section: Nitric Oxide-role In Cerebral Ischemic Preconditioningmentioning

confidence: 99%

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

Terpolilli¹,

Moskowitz

Plesnila³

2012

J Cereb Blood Flow Metab

128

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“…The concept of ischemic preconditioning shows indeed many parallels to the reduced susceptibility in many HD models: after a relatively mild brain ischemia, neurons are less susceptible to severe brain ischemia. 45 It has been suggested that mild activation of NMDA receptors is a central mechanism of developing ischemic tolerance. [46][47][48] Although several other interesting studies have demonstrated potential neuroprotective properties of different factors investigated in the context of HD, none of these factors have afforded the same dramatic protection against excitotoxicity as is in the transgenic HD mouse models we have described in this review article (see e.g.…”

Section: Possible Mechanisms Involved In Huntingtin-mediated Resistancementioning

confidence: 99%

Mutant huntingtin can paradoxically protect neurons from death

Züchner

Brundin

2007

Cell Death Differ

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Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1. An expansion of this CAG repeat above 35 results in misfolding of Huntingtin, giving rise to protein aggregates and neuronal cell death. There are several transgenic HD mouse models that reproduce most of the features of the human disorder, for example protein inclusions, some neurodegeneration as well as motor and cognitive symptoms. At the same time, a subgroup of the HD transgenic mouse models exhibit dramatically reduced susceptibility to excitotoxicity. The mechanism behind this is unknown. Here, we review the literature regarding this phenomenon, attempt to explain what protein domains are crucial for this phenomenon and point toward a putative mechanism. We suggest, that the C-terminal domain of exon 1 Huntingtin, namely the proline rich domain, is responsible for mediating a neuroprotective effect against excitotoxicity. Furthermore, we point out the possible importance of this mechanism for future therapies in neurological disorders that have been suggested to be associated with excitotoxicity, for example Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

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“…In the brain, Kitagawa et al (2) first reported that gerbils subjected to sublethal transient global ischemia exhibited reduced hippocampal neuronal death after a severe ischemic insult 24-28 h later. We have recently demonstrated in mixed neuron/astrocyte cultures that the ischemia-induced rise in the extracellular concentration of L-glutamate (Glu) is significantly suppressed by prior PC treatment, and this suppression during ischemia primarily contributes to the PC-induced ischemic tolerance of neurons (3).…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Produced During Sublethal Ischemia Is Crucial for the Preconditioning-Induced Down-Regulation of Glutamate Transporter GLT-1 in Neuron/Astrocyte Co-Cultures

et al. 2006

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Running head: nitric oxide and preconditioning-induced ischemic tolerance ------------------------------------------------------------------- AbstractIn the brain, prior sublethal ischemia (preconditioning, PC) produces tolerance of neurons to subsequent lethal ischemia. This study aims at elucidating whether and how nitric oxide (NO) produced during PC is involved in the PC-induced ischemic tolerance of neurons in neuron/astrocyte co-cultures. The rise in the extracellular concentration of glutamate during ischemia caused by the reversed uptake of glutamate (Glu) by the astrocytic Glu transporter GLT-1 was markedly suppressed by the prior PC treatment, but the suppression was reversed by treatment with an inhibitor of nitric oxide synthase (NOS) during PC. Immunocytochemical and Western blot analyses demonstrated that the expression of GLT-1 was down-regulated after the PC insult, and this down-regulation was also antagonized by treatment with NOS inhibitors during PC.Here we show that nNOS-derived NO produced during PC was crucial for the down-regulation of astrocytic GLT-1, and this down-regulation coincided with an increased survival rate of neurons.

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‘Ischemic tolerance’ phenomenon found in the brain

Cited by 1,026 publications

References 25 publications

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

Mutant huntingtin can paradoxically protect neurons from death

Nitric Oxide Produced During Sublethal Ischemia Is Crucial for the Preconditioning-Induced Down-Regulation of Glutamate Transporter GLT-1 in Neuron/Astrocyte Co-Cultures

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