Cell Culture Studies of the Role of Elevated Extracellular Glutamate and K+ in Neuronal Cell Death During and After Anoxia/Ischemia

Huang, Rong; Sochocka, Elzbieta; Hertz, Leif

doi:10.1016/s0149-7634(96)00002-4

Cited by 31 publications

(19 citation statements)

References 24 publications

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“…Indeed, interfering with the production of ATP by astrocytes results in pathophysiological changes similar to that seen in the ischemic penumbra, leading to the thesis that astrocyte dysfunction is the ultimate cause of neuronal death in the stroke penumbra (Largo et al, 1996). If one considers that a given volume of blood has five times as much glucose in it as there is oxygen for the oxidative metabolism of glucose (Huang et al, 1997), when astrocytes experience hypoxia or hypoxemia, the ability to upregulate the capacity to perform glycolysis might be the deciding factor determining whether astrocytes can perform their neuroprotective functions. It is .…”

Section: Resultsmentioning

confidence: 99%

Astrocytes respond to hypoxia by increasing glycolytic capacity

Marrif

Juurlink

1999

J. Neurosci. Res.

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Astrocytes cope more readily with hypoxic insults than do neurons. We hypothesized that astrocytes can upregulate their glycolytic capacity, allowing anaerobic glycolysis to provide sufficient ATP for cell survival as well as for carrying out critical functions such as taking up glutamate. To test this hypothesis, astrocytes were subjected to hypoxia for 5 hr. Lactate dehydrogenase (LDH) and pyruvate kinase activities increased 3- to 4-fold. Examination of LDH isoenzyme patterns determined that it was the anaerobic isoenzymes that were upregulated. To determine whether increase in enzyme activity translates into increased glycolytic capacity, astrocytes were subjected to varying time periods of hypoxia, and glucose uptake was measured under conditions where astrocytes were forced to consume more ATP. This demonstrated that 8 hr of hypoxia resulted in a doubling of glycolytic capacity. We suggest that how quickly astrocytes upregulate glycolytic capacity may determine whether or not neurons within the stroke penumbra survive.

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Section: Resultsmentioning

confidence: 99%

Astrocytes respond to hypoxia by increasing glycolytic capacity

Marrif

Juurlink

1999

J. Neurosci. Res.

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“…8 For example, ICH-induced elevation in TNF-␣ may impair the ability of astrocytes to remove extracellular glutamate through dysregulation of calcium homeostasis, as shown for other neurological diseases, including HIV 31,32 or ischemia. 33 TNF-␣ may also act on microglia and macrophages to increase proinflammatory cytokine production via activation of nuclear factor-B. 34,35 This would enhance reactive oxygen species, including nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

Antisense Oligodeoxynucleotide Inhibition of Tumor Necrosis Factor-α Expression Is Neuroprotective After Intracerebral Hemorrhage

Mayne

Yan

et al. 2001

Stroke

147

112

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Background and Purpose-Tumor necrosis factor-␣ (TNF-␣) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in intracerebral hemorrhage (ICH). A TNF-␣-specific antisense oligodeoxynucleotide (ORF4-PE) was used to study the extent to which TNF-␣ expression influenced neurobehavioral outcomes and brain damage in a collagenase-induced ICH model in rat. Methods-Male Sprague-Dawley rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Immediately before or 3 hours after ICH induction, ORF4-PE was administered directly into the site of ICH. TNF-␣ mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and immunoblot analyses. Cell death was measured by terminal deoxynucleotidyl transferase-mediated uridine 5Јtriphosphate-biotin nick end labeling (TUNEL). Neurobehavioral deficits were measured for 4 weeks after ICH. Results-ICH induction (nϭ6) elevated TNF-␣ mRNA and protein levels (PϽ0.01) at 24 hours after the onset of injury compared with sham controls (nϭ6). Immunohistochemical labeling indicated that ICH was accompanied by elevated expression of TNF-␣ in neutrophils, macrophages, and microglia. Administration of ORF4-PE (2.0 nmol) directly into striatal parenchyma, 15 minutes before (nϭ4) or 3 hours after (nϭ6) ICH, decreased levels of TNF-␣ mRNA (PϽ0.001) and protein (PϽ0.01) in the brain tissue surrounding the hematoma compared with animals treated with saline alone (nϭ6). MeanϮSEM striatal cell death (cells per high-powered field) was also reduced in animals receiving ORF4-PE (34.1Ϯ5.0) compared with the saline-treated ICH group (80.3Ϯ7.50) (PϽ0.001). ORF4-PE treatment improved neurobehavioral deficits observed at 24 hours (PϽ0.001) after induction of ICH (nϭ6) compared with the untreated ICH group (nϭ6). This improvement was maintained at 28 days after hemorrhage induction (PϽ0.001). Conclusions-These

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“…Inhibition of glutamate and glucose uptake by LPA is mediated through PTXinsensitive pathways [Keller et al, 1996[Keller et al, , 1997. The impairment of glutamate uptake could result in an increase in the extracellular glutamate level, which might exert neuronal toxicity [Huang et al, 1997].…”

Section: Astrocytesmentioning

confidence: 99%

LPA in neural cell development

Fukushima

2004

J of Cellular Biochemistry

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Lysophosphatidic acid (LPA) elicits diverse cellular responses through cell surface LPA receptors in nervous system-derived cells and cell lines. The developing nervous system is one of the major loci for LPA receptor expression. Recent studies have also revealed that metabolic pathways of LPA are present in the nervous system. A growing body of literature suggests a crucial role for LPA in neuronal development processes, including neurogenesis, neuronal migration, neuritogenesis, and myelination.

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Cell Culture Studies of the Role of Elevated Extracellular Glutamate and K+ in Neuronal Cell Death During and After Anoxia/Ischemia

Cited by 31 publications

References 24 publications

Astrocytes respond to hypoxia by increasing glycolytic capacity

Astrocytes respond to hypoxia by increasing glycolytic capacity

Antisense Oligodeoxynucleotide Inhibition of Tumor Necrosis Factor-α Expression Is Neuroprotective After Intracerebral Hemorrhage

LPA in neural cell development

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