Necrosis, apoptosis and hybrid death in the cortex and thalamus after barrel cortex ischemia in rats

Wei, Ling; Ying, Dajun; Cui, Lin; Langsdorf, Jennifer; Yu, Shan Ping

doi:10.1016/j.brainres.2004.06.080

Cited by 97 publications

(92 citation statements)

References 38 publications

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“…A delayed apoptotic cell death occurs in the thalamus in experimental stroke models after cortical stroke that is distant to the thalamus [87], and similarly in the substantia nigra after striatal stroke that is distant from the substantia nigra [81]. After white matter stroke, connected cortical areas suffer a delayed damage that is seen as cortical thinning in magnetic resonance imaging [88], and as an overall brain atrophy [89].…”

Section: Relayed Stroke: Effects Of Ischemia On Distant Connected Bramentioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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Section: Relayed Stroke: Effects Of Ischemia On Distant Connected Bramentioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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“…In ischemic brain, the generation of NO contributes to neuronal cell death, and NO production is mediated, at least in part, by excessive stimulation of NMDA-type glutamate receptors (35,36). Within 24 h of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO), cell death occurs by necrotic and apoptotic mechanisms (37). We surmised that the difference observed between the ischemic core (subcortex, including striatum) and penumbra (cortex) might be partly dependent on Akt/PTEN inactivation through S-nitrosylation.…”

Section: Sno-pten Inhibits Neuronal Apoptosismentioning

confidence: 99%

On–off system for PI3-kinase–Akt signaling through S -nitrosylation of phosphatase with sequence homology to tensin (PTEN)

Numajiri¹,

Takasawa²,

Nishiya

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

154

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Nitric oxide (NO) physiologically regulates numerous cellular responses through S-nitrosylation of protein cysteine residues. We performed antibody-array screening in conjunction with biotin-switch assays to look for S-nitrosylated proteins. Using this combination of techniques, we found that phosphatase with sequence homology to tensin (PTEN) is selectively S-nitrosylated by low concentrations of NO at a specific cysteine residue (Cys-83). S-nitrosylation of PTEN (forming SNO-PTEN) inhibits enzymatic activity and consequently stimulates the downstream Akt cascade, indicating that Cys-83 is a critical site for redox regulation of PTEN function. In ischemic mouse brain, we observed SNO-PTEN in the core and penumbra regions but found SNO-Akt, which is known to inhibit Akt activity, only in the ischemic core. These findings suggest that low concentrations of NO, as found in the penumbra, preferentially S-nitrosylate PTEN, whereas higher concentrations of NO, known to exist in the ischemic core, also S-nitrosylate Akt. In the penumbra, inhibition of PTEN (but not Akt) activity by S-nitrosylation would be expected to contribute to cell survival by means of enhanced Akt signaling. In contrast, in the ischemic core, SNO-Akt formation would inhibit this neuroprotective pathway. In vitro model systems support this notion. Thus, we identify unique sites of PTEN and Akt regulation by means of S-nitrosylation, resulting in an "on-off" pattern of control of Akt signaling.apoptosis | ischemia | oxidation N itric oxide (NO) exerts pleiotropic cellular responses on proliferation, apoptosis, neurotransmission, and neurotoxicity in several types of cells by means of protein S-nitrosylation. This modification occurs by means of oxidative reaction between NO and cysteine (Cys) thiol in the presence of an electron acceptor (such as O 2 or a transition metal) or through transnitrosylation from S-nitrosothiol to another Cys thiol (1-3). Several methods have been published to detect S-nitrosylated proteins (SNO-Ps) by using antibodies, photolysis, and mercury affinity (4). In particular, the biotin-switch assay is a modified immunoblot developed by Jaffrey and Snyder that has been commonly used to detect endogenous SNO-Ps; this method has greatly advanced the field (5). Subsequently, other methods have been developed to detect SNO-Ps (6), but some of them involve samples treated with high concentrations of NO donor. In the presence of high concentrations of NO, however, it is possible that some Cys residues are artifactually S-nitrosylated.Antibody arrays have been used to profile protein expression levels with high sensitivity. Each spotted antibody can be validated for its ability to bind proteins in the assay. Samples hybridizing to each antibody on the array can be easily detected. Although a number of proteins have been identified as substrates for S-nitrosylation in the past several years (3-6), we hypothesized that many more candidates modified by physiological levels of NO might still remain to be identified. We therefore teste...

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“…In addition, both apoptotic and necrotic death pathways occur in the same cell or appear in discrete cell groups, e.g. large chromatin clump, nuclear condensation/fragmentation, and swollen cytoplasm, damaged organelles and deteriorated membranes co-exist in the same neuron after transient and pMCAO models in rats [18][19][20] .…”

Section: Ischemic Neuronal Death: Necrosis and Apoptosismentioning

confidence: 99%

Mechanisms of lysosomal proteases participating in cerebral ischemia-induced neuronal death

2008

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Abstract:There are three different types of cell death, including apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). Ischemic neuronal death influences stroke development and progression. Lysosomes are important organelles having an acidic milieu to maintain cellular metabolism by degrading unneeded extra-and intracellular substances. Lysosomal enzymes, including cathepsins and some lipid hydrolases, when secreted following rupture of the lysosomal membrane, can be very harmful to their environment, which results in pathological destruction of cellular structures. Since lysosomes contain catalytic enzymes for degrading proteins, carbohydrates and lipids, it seems natural that they should participate in cellular death and dismantling. In this review, we discuss the recent developments in ischemic neuronal death, and present the possible molecular mechanisms that the lysosomal enzymes participate in the three different types of cell death in ischemic brain damage. Moreover, the research related to the selective cathepsin inhibitors may provide a novel therapeutic target for treating stroke and promoting recovery.

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Necrosis, apoptosis and hybrid death in the cortex and thalamus after barrel cortex ischemia in rats

Cited by 97 publications

References 38 publications

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

On–off system for PI3-kinase–Akt signaling through S -nitrosylation of phosphatase with sequence homology to tensin (PTEN)

Mechanisms of lysosomal proteases participating in cerebral ischemia-induced neuronal death

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