Progression of ischaemic stroke and excitotoxic aminoacids

Castillo, José; Dávalos, Antoni; Noya, M

doi:10.1016/s0140-6736(96)04453-4

Cited by 297 publications

(237 citation statements)

References 28 publications

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“…Several studies have described increases in brain (McBride et al, 1976;Gilad et al, 1990;Moghaddam, 1993) and plasma EAA levels (Milakofsky et al, 1985;De Cristóbal et al, 2002) following exposure to restraint or immobilization. Although glutamate concentration in this report has been determined in plasma, its increase after stress very likely reflects the profile of this EAA in the brain, as has been shown to be the case after cerebral ischemia (Baker et al, 1995;Castillo et al, 1997;De Cristóbal et al, 2001). It is well known that one of the main mechanisms of glutamate toxicity in neurodegenerative diseases is the oxidation of transporters which account for inhibition of EAA reuptake (Trotti et al, 1996).…”

Section: Discussionmentioning

confidence: 82%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

136

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Cyclooxygenase (COX) is the rate-limiting enzyme in the metabolism of arachidonic acid into prostanoids. Although it is constitutively expressed in brain neurons, the inducible isoform (COX-2) is also upregulated in pathological conditions such as seizures, ischemia or some degenerative diseases. To assess whether COX-2 is regulated after stress, we have used adult male Wistar rats, some of which were immobilized during 6 h. An increase in PGE 2 concentration occurs in brain cortex after 2-6 h of the onset of stress as well as an enhancement of COX-2 protein. Immunohistochemical studies indicate that COX-2 is expressed in the cortex and hippocampus after stress in cells with morphology of neurons. Administration of PDTC (150 mg/kg), an inhibitor of the transcription factor NF-kB or MK-801 (0.2 mg/kg), an N-methyl-D-aspartate receptor blocker, prevents both stress-induced increase in COX-2 activity and protein levels, suggesting an implication of these factors in the mechanism by which stress induces COX-2 in brain. To assess if COX-2 accounts for the oxidative status seen in brain after stress, a group of animals were i.p. injected with NS-398, a specific COX-2 inhibitor 1 h prior to the onset of stress. NS-398 (5 mg/kg) decreases stress-induced malondialdehyde accumulation in cortex as well as prevents the stressinduced oxidation of glutathione. Finally, NS-398 reduced Ca 2+ -independent inducible nitric oxide synthase (iNOS, NOS-2) activity and lowered the stress-induced accumulation of NO metabolite levels in cortex. These effects of NS-398 seem to be due to the specific inhibition of COX-2, since it has no effect on stress-induced corticosterone release, glutamate release, and NF-kB activation. These findings are discussed as possible damaging and/or adaptive roles for stress-induced COX-2 in the brain.

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Section: Discussionmentioning

confidence: 82%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

136

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“…In fact, previous studies by our group have shown that neurologic deterioration and infarct growth in acute ischemic stroke is associated with higher glutamate levels in blood (Castellanos et al, 2006;Castillo et al, 1996Castillo et al, , 1997.…”

Section: Discussionmentioning

confidence: 83%

“…It is a well-established fact that during brain ischemia, glutamate acts as an important mediator of neuronal degeneration; in fact, studies conducted by our group have shown that neurologic deterioration of patients with ischemic stroke is associated with higher glutamate levels in blood and cerebrospinal fluid (Castillo et al, 1996(Castillo et al, , 1997.…”

Section: Introductionmentioning

confidence: 94%

“…As ischemic stroke is associated with an excessive release of glutamate into the brain parenchyma (Castillo et al, 1996(Castillo et al, , 1997, a decrease in blood glutamate levels provides a mechanism to increase the gradient concentration and to remove this neurotransmitter from the brain at early times, with possible therapeutic implications after an ischemic insult (Gottlieb et al, 2003;Teichberg et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke

Campos

Sobrino

Blanco

et al. 2011

J Cereb Blood Flow Metab

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The capacity of the blood enzyme glutamate oxaloacetate transaminase (GOT) to remove glutamate from the brain by means of blood glutamate degradation has been shown in experimental models to be an efficient and novel neuroprotective tool against ischemic stroke; however, the beneficial effects of this enzyme should be tested in patients with stroke to validate these results. This study aims to investigate the association of GOT levels in blood with clinical outcome in patients with acute ischemic stroke. In two clinical independent studies, we found that patients with poor outcome show higher glutamate and lower GOT levels in blood at the time of admission. Lower GOT levels and higher glutamate levels were independently associated with poorer functional outcome at 3 months and higher infarct volume. These findings show a clear association between high blood glutamate levels and worse outcome and vice versa for GOT, presumably explained by the capacity of this enzyme to metabolize blood glutamate.

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“…Both plasma and CSF glutamate levels are elevated in patients who experience END [67,68]. Patients with hemispheric strokes with levels of glutamate in plasma >200 umol/l and CSF >8.2 umol/l predicted END with a probability of 92 and 93% respectively [69].…”

Section: Biomarkers To Predict Early Neurological Deteriorationmentioning

confidence: 99%

Blood Biomarkers of Ischemic Stroke

2011

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This review provides a summary of the protein and RNA biomarkers that have been studied for the diagnosis and assessment of ischemic stroke. Many of the biomarkers identified relate to the pathophysiology of ischemic stroke, including ischemia of CNS tissue, acute thrombosis and inflammatory response. These biomarkers are summarized by their intended clinical application in ischemic stroke including diagnosis, prediction of stroke severity and outcome, and stratification of patients for stroke therapy. Among the biomarkers discussed are recent whole genome studies using RNA expression profiles to diagnose ischemic stroke and stroke etiology. Though many candidate blood based biomarkers for ischemic stroke have been identified, none are currently used in clinical practice. With further well designed study and careful validation, the development of blood biomarkers to improve the care of patients with ischemic stroke may be achieved.

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Progression of ischaemic stroke and excitotoxic aminoacids

Cited by 297 publications

References 28 publications

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke

Blood Biomarkers of Ischemic Stroke

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