Anoxic depolarization determines ischemic brain injury

Kaminogo, Makio; Suyama, Kazuhiko; Ichikura, Akio; Onizuka, Masanari; Shibata, Shôbu

doi:10.1080/01616412.1998.11740529

Cited by 50 publications

(37 citation statements)

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“…With regard to the latter, cellular depolarization is clearly detrimental to the ultimate outcome in models of cerebral ischemia. 1) Ischemic neuronal damage subsequent to transient global ischemia or hypoxia correlates closely with the duration of anoxic depolarization (20,187,283,374), and 2) the size of infarct in stroke models increases with the number and total duration of peri-infarct depolarizing events (250,408). In addition, brain cells appear to have the ability to adapt to hypoxia by reducing their energy demand through modulation of ion channels, which delays anoxic depolarization (150,162,419,437).…”

Section: A Cellular Ionic Homeostasis and Energy Metabolismmentioning

confidence: 99%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.

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Section: A Cellular Ionic Homeostasis and Energy Metabolismmentioning

confidence: 99%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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Section: Rvt Attenuates Ogd Induced Neuronal Excitability Impairment mentioning

confidence: 99%

“…As the AD occurs soon after the beginning of severe hypoxia or cerebral ischemia, neuroprotectants that are able to delay this process should be beneficial for rescuing neurons if given very early. Although the mechanism underlying AD is still not fully understood, the massive Ca 2+ influx via activated NMDA receptors leading to irreversible neuronal damage is an essential contributing mechanism (Balestrino et al, 1995;Kaminogo et al, 1998).According to the report by Onitsuka et al (1998) the reversible neuronal Vm depolarization phase can last for 14.4 min at 27 oC. In order to determine RVT neuroprotection, we used room temperature so that the RVT effects on neuronal excitability can be reliably measured in this reversible ischemia in vitro model, which is consistent with our observation that the 15 min.…”

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confidence: 99%

Resveratrol attenuates early pyramidal neuron excitability impairment and death in acute rat hippocampal slices caused by oxygen-glucose deprivation

Zhang

Schools²,

Lei

et al. 2008

Experimental Neurology

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Accumulating evidence indicates that the polyphenol resveratrol (trans-3, 5, 4′-trihydroxystibene, RVT) potently protects against cerebral ischemia neuronal damage due to its oxygen free radicals scavenging and antioxidant properties. However, it is unknown whether RVT can attenuate ischemiainduced early impairment of neuronal excitability. To address this question, we simulated ischemic conditions by applying oxygen-glucose deprivation (OGD) to acute rat hippocampal slices and examined the effect of RVT on OGD-induced pyramidal neuron excitability impairment using wholecell patch clamp recording. 100 μM RVT largely inhibited the 15 min OGD-induced progressive membrane potential (Vm) depolarization and the reduction in evoked action potential frequency and amplitude in pyramidal neurons. In the parallel neuronal viability study using TO-PRO-3 iodide staining, 20 min OGD induced irreversible CA1 pyramidal neuronal death which was significantly reduced by 100 μM RVT. No similar effects were found with PQQ treatment, an antioxidant also showing potent neuroprotection in the rat rMCAO ischemia model. This suggests that antioxidant action per se, is unlikely accounting for the observed early effects of RVT. RVT also markedly reduced the frequency and amplitude of AMPA mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons, which is also an early consequence of OGD. RVT effects on neuronal excitability were inhibited by the large conductance potassium channel (BK channel) inhibitor paxilline. Together, these studies demonstrate that RVT attenuates OGD induced neuronal impairment occurring early in the simulated ischemia slice model by enhancing the activation of BK channel and reducing the OGD-enhanced AMPA/NMDA receptor mediated neuronal EPSCs. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access INTRODUTIONRecent studies have shown that resveratrol (RVT) can protect ischemia damage in a variety of organs, such as brain, kidney and heart (Ray, et al., 1999; Bastianetto et al., 2000;Chander and Chopra, 2006). RVT is one of the primary active polyphenol compounds identified in red wine (Jang et al., 1997; Bastianetto et al., 2000;Oak et al., 2005), which has attracted increasing research interest on how this compound could offer such a miracle protection. Mechanistically, RVT acts as a potent antioxidant and scavenger of hydroperoxyl free radicals (Pace-Asciak et al., 1996; Mokni et al., 2006;Das et al., 2006). These protective actions of RVT in cerebral ischemia have so far been identified from studies in vivo and in cultured n...

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“…Delay of AD may be relevant to neuroprotection in stroke, because AD is a factor in the generation of anoxic damage, and its delay has been associated with better outcome under experimental conditions (Balestrino and Somjen, 1986;Jarvis et al, 2001;Kaminogo et al, 1998;Somjen et al, 1990). The present study indicates that significant delay of AD is obtained at mannitol concentrations greater than 10 mM, 25 mM being the lowest effective dose among those tested.…”

Section: Discussionmentioning

confidence: 99%

“…However, increasing extracellular osmolarity has direct effects on neuronal electrical function (Osehobo and Andrew, 1993;Rudehill et al, 1993), and one of us has previously reported that adding mannitol to the perfusing medium of brain slices delays anoxic depolarization (AD) (Balestrino, 1995a;Balestrino, 1995b). Since the latter is a factor in causing neuronal damage in anoxia and ischemia (Balestrino and Somjen, 1986;Jarvis et al, 2001;Kaminogo et al, 1998;Somjen et al, 1990), this may be another mechanism of brain protection by hyperosmotic agents in stroke. This study investigates whether or not this delay occurs at values of hyperosmolarity that may be obtained in clinical practice.…”

Section: Introductionmentioning

confidence: 99%