Carnosine Is Neuroprotective Against Permanent Focal Cerebral Ischemia in Mice

Rajanikant, G. K.; Zemke, Daniel; Senut, Marie-Claude; Frenkel, Mark B.; Chen, Alex F.; Gupta, Rishi; Majid, Arshad

doi:10.1161/strokeaha.107.488502

Cited by 120 publications

(88 citation statements)

References 17 publications

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“…In the same study, it has also been shown to reduce the accumulation of malondialdehyde, a marker of lipid peroxidation, in the brains of animals subjected to an ischemic episode. Pretreatment with carnosine has also been reported as effective in decreasing infarct size, neuronal damage, and ROS levels in models of permanent cerebral ischemia [14][15][16]. The application of carnosine in vitro has also been reported to be partially effective in protecting neuronal cultures against damage induced by amyloid-␤ (A␤) [17].…”

Section: B Herculano Et Al / Carnosine Rescues Cognitive Declinementioning

confidence: 99%

β-Alanyl-L-Histidine Rescues Cognitive Deficits Caused by Feeding a High Fat Diet in a Transgenic Mouse Model of Alzheimer's Disease

Herculano

Tamura

Ohba

et al. 2013

JAD

113

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Abstract. Our goal in this study was to determine whether or not feeding young (4 months old) Alzheimer's disease model transgenic mice with a high fat diet (HFD), consisting of 32% fat, is capable of causing cognitive decline and whether treatment with ␤-alanyl-L-histidine (carnosine) is capable of reducing these effects. Carnosine is an endogenous antioxidant and antiglycating agent that is abundantly present in the brain and muscle tissues of vertebrates. After 8 weeks of feeding with HFD, we observed a significant decline in the contextual memory in transgenic mice fed with HFD as compared to transgenic mice fed with a normal diet as well as to normal diet-wild type mice. Treatment with carnosine at a dose of 5 mg/day for 6 weeks was effective in preventing cognitive decline, as the transgenic group fed with HFD and treated with carnosine displayed a level of cognition comparable to controls. No differences in senile plaque load were observed between all groups. However, we observed an increase in the expression of RAGE in blood vessels as well as increased microglial activation in the hippocampus of animals fed with HFD, effects that were reversed when treated with carnosine. Given these results, there is a possibility that inflammation and cerebrovascular abnormalities might be the cause of cognitive decline in this model.

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Section: B Herculano Et Al / Carnosine Rescues Cognitive Declinementioning

confidence: 99%

β-Alanyl-L-Histidine Rescues Cognitive Deficits Caused by Feeding a High Fat Diet in a Transgenic Mouse Model of Alzheimer's Disease

Herculano

Tamura

Ohba

et al. 2013

JAD

113

View full text Add to dashboard Cite

show abstract

“…3). Recently, carnosine has been shown to protect cultured neurons from oxygen glucose deprivation and to exhibit neuroprotective properties in animal models of global and cerebral ischemia (17,38,39). Therefore, our data suggest that carnosine and anserine may be attractive candidate for treatment of neurodegenerative disorders.…”

Section: Resultsmentioning

confidence: 65%

Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative modification of neurofilament-L: protection by histidyl dipeptides

Kang¹

2012

BMB Reports

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Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (•OH) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification.

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“…Artery access is achieved by craniotomy and occlusion is verified by laser-Doppler. 5 Controls consist of unligated left MCA and sham operated rats. After 24 h, MCA segments located upstream and downstream to the ligature are investigated for expressional changes of ET, AT and 5-HT receptors at protein (immunohistochemistry) and functional (myograph) level.…”

Section: Discussionmentioning

confidence: 99%

Brain Poster Session: Experimental Cerebral Ischemia—Vascular and Endothelial

2009

J Cereb Blood Flow Metab

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Objective: The objective of this study was to determine whether the long-term administration of an HMG-CoA reductase inhibitor, atorvastatin, confers antioxidative effect in microvessels in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). Method: Atorvastatin (20 mg/kg) or vehicle was orally administered to 8-week-old SHRSPs for 5 weeks. As normal controls, vehicle was orally administered to 8-week-old WKYs over the same period. The animals were decapitated and the brains were removed. The brains were then quickly frozen, and were sliced into horizontal sections of 6-mm-thickness using a cryostat. The markers for oxidative stresses on lipids (4HNE) and DNA (8OHdG) were immunohistochemically detected. The numbers of positive vessels in the 6 randomized 0.25 mm 2 areas in a horizontal section were counted. The ratio of positive vessels for each maker to all vessels (positive for von Wille brand factor) was calculated.Results: The positive ratio of oxidative stress markers was significantly higher in the vehicle group than in the normal controls. Then the positive ratio was significantly lower in the atorvastatin group than in the vehicle group. Atorvastatin significantly reduced immunoreactivities for oxidative stress markers in microvessels. Lipids such as total cholesterol (T-cho), HDL-cholesterol (HDL-cho), LDL-cholesterol (LDL-cho), and triglyceride (TG) did not differ among the vehicle, the statin, and normal control groups. Conclusions:The results suggest that statins may confer the antioxidative properties and have the protective effects in the endothelial cells, even in the brain microvessels.35. Concomitant treatment with medroxyprogesterone and conjugated equine estrogens attenuates estrogen's protective effect on postischemic pial artery vasodilation to acetylcholine C. Miyazaki 1 , E. Zeynalov 1 and M. LIttleton-Kearney 2 1 Anesthesia/Critical Care Medicine; 2 Nursing/Anesthesia Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA Background and aims: Chronic estrogen replacement partially preserves postischemic pial arteriole vasodilation to endothelium-dependent vasodilators. It is unclear if concomitantly administered equine estrogens (EE) and medroxyprogesterone (MP), hormone replacement therapy commonly prescribed for women, alters estrogen's effect on postischemic pial arterial vasodilation. We determined if:(1) EE preserves postischemic pial artery dilation to acetylcholine (Ach), (2) concomitant administration of MP and EE alters the effect of EE alone on postichemic Ach-evoked dilation, (3) natural hormone depletion associated with aging depresses postischemic pial artery Ach-evoked dilation, and (4) concomitantly administered EE and MP has the same effect on postischemic pial artery dilation in young ovariectomized (OVX) and aged reproducively senescent rats (RS).Methods: Young OVX (2 to 3.5 months) or aged RS female rats (20 to 22 months) were used for these studies. The young groups included; OVX, EE-treated (EE) and EE plus MP (EEMP). The aged group...

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Carnosine Is Neuroprotective Against Permanent Focal Cerebral Ischemia in Mice

Cited by 120 publications

References 17 publications

β-Alanyl-L-Histidine Rescues Cognitive Deficits Caused by Feeding a High Fat Diet in a Transgenic Mouse Model of Alzheimer's Disease

β-Alanyl-L-Histidine Rescues Cognitive Deficits Caused by Feeding a High Fat Diet in a Transgenic Mouse Model of Alzheimer's Disease

Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative modification of neurofilament-L: protection by histidyl dipeptides

Brain Poster Session: Experimental Cerebral Ischemia—Vascular and Endothelial

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