Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease

Ryu, Jae K.; Kim, Seung Up; McLarnon, James G.

doi:10.1016/j.expneurol.2004.01.006

Cited by 53 publications

(51 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The four immunostained sections (AP, ϩ1.4, ϩ1.2, ϩ1.0, and ϩ0.8) were digitized and analyzed using image analysis program NIH version 1.57 (Wayne Rasband, National Institutes of Health, Bethesda, MD) as described previously (Ryu et al, 2004 …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Choi

Ryu²,

Kim³

et al. 2007

J. Neurosci.

153

119

View full text Add to dashboard Cite

We investigated the involvement and roles of the ionotropic purinergic receptor P2X 7 R in microglia in mediating lipopolysaccharide (LPS)-induced inflammatory responses and neuronal damage in rat striatum. A detailed in vivo study showed that LPS injection into striatum markedly increased the expression of P2X 7 R in microglia compared with control (saline)-injected animals. Additionally, LPS injection upregulated a broad spectrum of proinflammatory mediators, including inducible nitric oxide synthase (nitric oxide production marker), 3-nitrotyrosine (peroxynitrite-mediated nitration marker), 4-hydroxynonenal (lipid peroxidation marker), and 8-hydroxy-2Ј-deoxyguanosine (oxidative DNA damage marker), and reduced neuronal viability. The P2X 7 R antagonist oxidized ATP (oxATP) was effective in attenuating expressions of all inflammatory mediators and in addition inhibited LPS-induced activation of the cellular signaling factors p38 mitogen-activated protein kinase and transcriptional factor nuclear factor B.

show abstract

Section: Methodsmentioning

confidence: 99%

“…We studied this point by measuring neuronal viability in LPS-injected striatum (5 g for 3 d) in the absence and presence of oxATP. Neuronal viability was assessed by counting immunostained neurons using NeuN antibody (Dou et al, 2003;Ryu et al, 2004). A typical result is shown in Figure 7A.…”

Section: Effects Of Oxatp On Lps-induced Neuronal Loss and Caspase-3 mentioning

confidence: 99%

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Choi

Ryu²,

Kim³

et al. 2007

J. Neurosci.

153

119

View full text Add to dashboard Cite

show abstract

“…after onset of reperfusion significantly decreased mortality, neuronal zinc accumulation, and neuronal cell death in a rat model of transient global ischemia (Lee et al, 2001). Although a subsequent study found no benefits of SP treatment after permanent middle cerebral artery occlusion (Gonzalez-Falcon et al, 2003), significant neurological improvements or neuroprotective effects after one SP treatment have been reported in rodent models of transient or permanent ischemia (Yoo et al, 2004;Yi et al, 2007), quinolinic acid-induced injuries (Ryu et al, 2003(Ryu et al, , 2004, kainic acid-induced epilepsy , and hypoglycemia (Suh et al, 2005).…”

mentioning

confidence: 97%

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

Fukushima

Lee

Moro

et al. 2009

Journal of Neurotrauma

View full text Add to dashboard Cite

This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD glc ), lactate (MD lac ), and pyruvate (MD pyr ), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg=kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate ( p < 0.005) and lactate ( p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats ( p < 0.05), but not in Sham-SP rats. MD pyr was not altered after CCI-Sal, whereas MD lac levels within the cerebral cortex significantly increased bilaterally ( p < 0.05) and those for MD glc decreased bilaterally ( p < 0.05). MD pyr levels increased significantly in both Sham-SP and CCI-SP rats ( p < 0.05 vs. CCI-Sal) and were higher in left=injured cortex of the CCI-SP group ( p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD lac decreased below CCI-Sal levels ( p < 0.05) and the ipsilateral MD glc levels exceeded those of CCI-Sal rats ( p < 0.05). Rats with a single low (500 mg=kg) or high dose (1000 mg=kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats ( p < 0.05), but three hourly injections of SP (1000 mg=kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI.

show abstract

“…Increasing mitochondrial antioxidant activities by elevating mitochondrial reducing power is considered as an important mechanism of neuroprotection by several naturally occurring compounds, including ketone bodies, pyruvate, and acyl-carnitines (Ryu et al, 2004;Zanelli et al, 2005;Gasior et al, 2006;Zhao et al, 2006b;Jarrett et al, 2008;Rosca et al, 2009;Alves et al, 2009;Jones et al, 2010;Zhang et al, 2010). This mechanism of action might be particularly important during reperfusion after cerebral ischemia, when the mitochondrial redox state is hyperoxidized, ROS production is elevated, and there are increased markers of oxidative molecular modification (Perez-Pinzon et al, 1999;Fiskum et al, 2004).…”

Section: Protection Against Mitochondrial Oxidative Stressmentioning

confidence: 99%

Novel Mitochondrial Targets for Neuroprotection

Pérez-Pinzón

Stetler

Fiskum

2012

J Cereb Blood Flow Metab

130

108

View full text Add to dashboard Cite

Mitochondrial dysfunction contributes to the pathophysiology of acute neurologic disorders and neurodegenerative diseases. Bioenergetic failure is the primary cause of acute neuronal necrosis, and involves excitotoxicity-associated mitochondrial Ca 2 + overload, resulting in opening of the inner membrane permeability transition pore and inhibition of oxidative phosphorylation. Mitochondrial energy metabolism is also very sensitive to inhibition by reactive O 2 and nitrogen species, which modify many mitochondrial proteins, lipids, and DNA/RNA, thus impairing energy transduction and exacerbating free radical production. Oxidative stress and Ca 2 + -activated calpain protease activities also promote apoptosis and other forms of programmed cell death, primarily through modification of proteins and lipids present at the outer membrane, causing release of proapoptotic mitochondrial proteins, which initiate caspase-dependent and caspase-independent forms of cell death. This review focuses on three classifications of mitochondrial targets for neuroprotection. The first is mitochondrial quality control, maintained by the dynamic processes of mitochondrial fission and fusion and autophagy of abnormal mitochondria. The second includes targets amenable to ischemic preconditioning, e.g., electron transport chain components, ion channels, uncoupling proteins, and mitochondrial biogenesis. The third includes mitochondrial proteins and other molecules that defend against oxidative stress. Each class of targets exhibits excellent potential for translation to clinical neuroprotection.

show abstract

Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease

Cited by 53 publications

References 38 publications

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

Novel Mitochondrial Targets for Neuroprotection

Contact Info

Product

Resources

About

Blockade of quinolinic acid-induced neurotoxicity by pyruvate is associated with inhibition of glial activation in a model of Huntington's disease

Cited by 53 publications

References 38 publications

Modulation of the Purinergic P2X7Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Modulation of the Purinergic P2X7Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Metabolic and Histologic Effects of Sodium Pyruvate Treatment in the Rat after Cortical Contusion Injury

Novel Mitochondrial Targets for Neuroprotection

Contact Info

Product

Resources

About

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain

Modulation of the Purinergic P2X₇Receptor Attenuates Lipopolysaccharide-Mediated Microglial Activation and Neuronal Damage in Inflamed Brain