Attenuation of Glutamate-induced Neuronal Swelling and Toxicity in Transgenic Mice Overexpressing Human CuZn-Superoxide Dismutase

Chan, Pak H.; Chu, Luke L. H.; Chen, S. F.; Carlson, Elaine J.; Epstein, Charles J.

doi:10.1007/978-3-7091-9115-6_82

Cited by 52 publications

(52 citation statements)

References 11 publications

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“…Transgenic mice overexpressing human copper-zinc superoxide dismutase have been of great value in demonstrating a relation between glutamate toxicity and reactive oxygen species. Glutamate-induced swelling and death are significantly reduced in cultures of primary cortical neurons of these mice, relative to normal non-transgenic littermates 11 • A recent report has found kainic acid administered in vivo, to elevate rates of lipid peroxidation in both cerebellum and hippocampus 41 . While there is a correlation between excitotoxicity and free radical generation, an unequivocal causal relation remains to be uncovered. Transient ischemia elevates cerebral levels of both excitatory amino acids and rates of hydroxyl radical formation 15 .…”

Section: Discussionmentioning

confidence: 90%

Oxidative stress induced by glutamate receptor agonists

Bondy¹,

Lee²

1993

Brain Research

198

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The effect of various selective glutamate agonists upon the rate of generation of reactive oxygen species (ROS), was examined in an isolated synaptoneurosomal (microsac) fraction derived from rat cerebral cortex. The rates of ROS generation were determined by a fluorescent probe. Agonists specific for each of the three major glutamate inotropic receptor sites (NMDA, kainic acid, a-amino-3-hydroxy-5-methyl-4-isoxalolpropionic acid, AMPA), were able to enhance rates of ROS generation. The metabotropic glutamate agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid, (ACPD), was inactive in this regard. Stimulation of ROS was most pronounced in the case of kainate. Such results could not be replicated by use of ion-channel active agents, veratridine and A23817. Pretreatment with the kainate antagonist, 6-cyano-7-quinoxaline-2,3-dione (CNQX), was not able to block the kainate-induced elvation of ROS. Domoic acid, a kainate agonist, also enhanced microsac ROS generation. Neurological damage may result from generation of excess free radicals, and this may be effected by glutamate agonists acting by means independent of their ionotropic properties.

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Section: Discussionmentioning

confidence: 90%

Oxidative stress induced by glutamate receptor agonists

Bondy¹,

Lee²

1993

Brain Research

198

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“…Increased levels of CuZn-SOD coupled with the presence of glutathione peroxidase may have eliminated the precursors needed for the Haber-Weiss reaction. 39 It is also possible that chronic oxidative stress, having developed in mice that overexpress CuZn-SOD, may have protected the cells paradoxically through preconditioning. 15 Another possible route to cell death is through the formation of peroxynitrite from nitric oxide and superoxide.…”

Section: Cell Death and Cuzn-sodmentioning

confidence: 99%

“…Overexpression of CuZn-SOD has been shown to protect against glutamate neurotoxicity. 39 The specific mechanism by which CuZn-SOD protects against hemolysate-induced cell damage will form the basis for further studies in these mutant mice.…”

Section: Cell Death and Cuzn-sodmentioning

confidence: 99%

Cell Death After Exposure to Subarachnoid Hemolysate Correlates Inversely With Expression of CuZn–Superoxide Dismutase

Matz

Copin

Chan

2000

Stroke

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Background and Purpose-Subarachnoid hemolysate (SAH) has been associated with oxidative brain injury, cell death, and apoptosis. We hypothesized that over-expression of CuZn-superoxide dismutase (CuZn-SOD) would protect against injury after SAH, whereas reduction of its expression would exacerbate injury. Methods-Saline (nϭ16) or hemolysate (nϭ50) was injected into transgenic mice overexpressing CuZn-SOD (SOD1-Tg), CuZn-SOD heterozygous knockout mutants (SOD1ϩ/Ϫ), and wild-type littermates (Wt

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“…Although several antioxidant enzymes (including superoxide dismutases [SODs], glutathione peroxidases, and catalase) process these oxygen radicals, when they are overproduced, they generally exceed the capacity of the endogenous antioxidant enzymes, causing oxidative stress or injury of brain cells during reperfusion after an ischemic insult. We have demonstrated that overexpression of cytosolic copper zinc (CuZn) SOD in transgenic (Tg) mice plays a protective role in several types of brain injury, including cold-injury-induced brain edema , transient focal cerebral ischemia (Kondo et al, 1997b), traumatic brain injury (Mikawa et al, 1996), and hypoxic and excitotoxic neuronal injury in cultures (Chan et al, 1990;Copin et al, 1996). Although reperfusion after transient global cerebral ischemia resulting from cardiac arrest is known to produce oxygen radicals that damage selective vulnerable neurons, it is not clear whether increased CuZn SOD activity will provide neuroprotection against this ischemic insult.…”

mentioning

confidence: 99%

Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion

et al. 1998

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Transient global cerebral ischemia resulting from cardiac arrest is known to cause selective death in vulnerable neurons, including hippocampal CA 1 pyramidal neurons. It is postulated that oxygen radicals, superoxide in particular, are involved in cell death processes. To test this hypothesis, we first used in situ imaging of superoxide radical distribution by hydroethidine oxidation in vulnerable neurons. We then generated SOD1 transgenic (Tg) rats with a five-fold increase in copper zinc superoxide dismutase activity. The Tg rats and their non-Tg wild-type littermates were subjected to 10 min of global ischemia followed by 1 and 3 d of reperfusion. Neuronal damage, as assessed by cresyl violet staining and DNA fragmentation analysis, was significantly reduced in the hippocampal CA 1 region, cortex, striatum, and thalamus in SOD1 Tg rats at 3 d, as compared with the non-Tg littermates. There were no changes in the hippocampal CA 3 subregion and dentate gyrus, resistant areas in both SOD1 Tg and non-Tg rats. Quantitative analysis of the damaged CA 1 subregion showed marked neuroprotection against transient global cerebral ischemia in SOD1 Tg rats. These results suggest that superoxide radicals play a role in the delayed ischemic death of hippocampal CA 1 neurons. Our data also indicate that SOD1 Tg rats are useful tools for studying the role of oxygen radicals in the pathogenesis of neuronal death after transient global cerebral ischemia.

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Attenuation of Glutamate-induced Neuronal Swelling and Toxicity in Transgenic Mice Overexpressing Human CuZn-Superoxide Dismutase

Cited by 52 publications

References 11 publications

Oxidative stress induced by glutamate receptor agonists

Oxidative stress induced by glutamate receptor agonists

Cell Death After Exposure to Subarachnoid Hemolysate Correlates Inversely With Expression of CuZn–Superoxide Dismutase

Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion

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