Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen species

Boldyrev, Alexander A.; Song, R.; Lawrence, David A.; Carpenter, David O.

doi:10.1016/s0306-4522(99)00273-0

Cited by 92 publications

(42 citation statements)

References 45 publications

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“…In vitro and in vivo studies have revealed that carnosine can exert neuroprotective effects through various mechanisms such as cytosolic buffering capabilities, broad antioxidant activity, antiglutamatergic excitotoxicity, and metal ion-chelating properties. [5][6][7][8] Therefore, carnosine, through its diverse pharmacological activities, could have potential neuroprotective benefits against cerebral ischemia.…”

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confidence: 99%

Carnosine Is Neuroprotective Against Permanent Focal Cerebral Ischemia in Mice

Rajanikant

Zemke

Senut

et al. 2007

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120

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Background and Purpose-Carnosine is a naturally occurring dipeptide with multiple neuroprotective properties. In addition, it is well tolerated in high doses with minimal side effects. The purposes of this study were to determine whether carnosine is neuroprotective in permanent focal cerebral ischemia and to determine potential mechanisms of neuroprotection. Methods-We investigated the efficacy of carnosine in a mouse model of permanent focal cerebral ischemia. The effects of carnosine were investigated with respect to neuronal damage and infarct formation, endogenous antioxidant status, and matrix metalloproteinase activity. Results-Carnosine significantly decreased infarct size and neuronal damage when administered at time points both before and after the induction of ischemia. Carnosine also decreased reactive oxygen species levels in the ischemic brain, preserved normal glutathione levels, and decreased matrix metalloproteinase protein levels and activity. Conclusions-Carnosine is neuroprotective in focal cerebral ischemia and appears to influence deleterious pathological processes that are activated after the onset of ischemia.

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confidence: 99%

Carnosine Is Neuroprotective Against Permanent Focal Cerebral Ischemia in Mice

Rajanikant

Zemke

Senut

et al. 2007

Stroke

120

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“…6 Because apoptosis is a multistep process, with the lag phase lasting a significant amount of time, it is possible that agents that block the apoptotic cascade may inhibit the completion of programmed cell death, potentially saving injured cells. [5][6][7][8] To determine whether such therapy is warranted, an in vivo noninvasive imaging marker that identifies cells committed to apoptosis is necessary.…”

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confidence: 99%

^99m Tc Annexin V Imaging of Neonatal Hypoxic Brain Injury

D’Arceuil

Rhine

Crespigny

et al. 2000

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Background and Purpose: -Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII. Methods-Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (nϭ17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with 99m Tc annexin V. Radionuclide images were recorded 2 hours later. Results-Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier. Conclusions-Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

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“…So, it protects the tissues from these damaging 'second-wave' chemicals. For example, it blocks a highly reactive lipid peroxidation end-product called malondialdehyde (MDA) (Kohen et al, 1988;Aruoma et al, 1989;Hipkiss et al, 1997;Boldyrev, Song et al, 1999). MDA, if left uncontrolled, can cause damage to lipids, enzymes and DNA, and plays a part in the process of atherosclerosis, joint inflammation, cataract formation, and aging in general.…”

Section: General Effects Of Carnosinementioning

confidence: 99%

“…It also prevents the cross-linking of the macromolecules and promotes modification in enzyme-mediated protein degradation. Carnosine is widely believed to be an antioxidant which stabilizes and protects the cell membrane, and an oxygen free radical-scavenger (Kohen et al, 1988;Aruoma, Laughton et al, 1989;Boldyrev, Song et al, 1999). Specifically, as a water-soluble free radical scavenger it prevents lipid peroxidation within the cell membrane (Tamba & Torreggiani, 1999).…”

Section: General Effects Of Carnosinementioning

confidence: 99%