Intraischemic Hypothermia Decreases the Release of Glutamate in the Cores of Permanent Focal Cerebral Infarcts

Baker, C.J.; Fiore, Amory J.; Frazzini, Vincent I.; Choudhri, Tanvir F.; Zubay, Geoffrey P.; Solomon, Robert A.

doi:10.1097/00006123-199505000-00016

Cited by 19 publications

(23 citation statements)

References 59 publications

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“…Later, Benveniste et al 8 observed an increase in glutamate in the hippocampus of rats after ischemia. Baker et al 28 detected slower, less intense and shorter lasting elevation of glutamate in the ischemic hemisphere of hypothermic animals, in agreement with fi ndings of lower histological injury. A recent study from our institution using permanent focal CI in rats demonstrated a progressive reduction in total glutamate levels on the injured side after 30 and 45 minutes, which was not infl uenced by previous ketoprofen administration 13 .…”

Section: Discussionsupporting

confidence: 61%

Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia

Silva

Colli

Coimbra

et al. 2007

Arq. Neuro-Psiquiatr.

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-Objective: To study the neurobehavioral, biochemical and histopathological consequences of permanent focal brain ischemia, and the putative neuroprotective action of ketoprofen. Method: Onehundred-and-three Wistar rats divided into groups A and B were respectively submitted to 48 hours and 15 days of ischemia. Each group was divided into 4 subgroups: ischemic not treated, ischemic treated, sham not treated, and sham treated. Ischemic animals had the left middle cerebral artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes before arterial coagulation (manipulation in the sham group). Results: Exploratory activity and defecation were reduced in all ischemic animals in the first postoperative days and constant histopathological changes were observed in each group. The total brain glutamate levels were higher in treated animals 48 hours after surgery. Conclusion: No clear parallelism among behavioral, biochemical and histopathological findings was observed. Ketoprofen demonstrated no neuroprotective effect on the behavioral or histopathological aspects of focal permanent brain ischemia.KEY WORDS: focal brain ischemia, rat, open field, glutamate, histopathology, neuroprotection, ketoprofen. Avaliação do efeito neuroprotetor do cetoprofeno em ratos submetidos à isquemia cerebral focal permanenteRESUMO -Objetivo: Estudar as conseqüências comportamentais, bioquímicas e histopatológicas da isquemia cerebral focal permanente e o possível efeito neuroprotetor do cetoprofeno. Método: Foram utilizados 103 ratos Wistar, divididos em grupos A e B, submetidos, respectivamente, a 48 horas e a 15 dias de isquemia. Cada grupo foi dividido em 4 subgrupos: isquêmico não tratado; isquêmico tratado; sham não tratado; sham tratado. Nos animais isquêmicos foi coagulada a artéria cerebral média esquerda. Os subgrupos tratados receberam cetoprofeno 15 minutos antes da oclusão ou manipulação arterial. Resultados: Os animais isquêmicos reduziram a atividade exploratória e as evacuações nos primeiros dias pós-operatórios e mostraram alterações histopatológicas constantes em cada grupo. As concentrações do glutamato total 48 horas após a cirurgia foram maiores nos animais tratados. Conclusão: Não houve um paralelismo entre os achados comportamentais, bioquímicos e histopatológicos. O cetoprofeno não apresentou efeito protetor contra isquemia cerebral focal permanente, nos aspectos comportamentais e histopatológicos.

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Section: Discussionsupporting

confidence: 61%

Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia

Silva

Colli

Coimbra

et al. 2007

Arq. Neuro-Psiquiatr.

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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: 79%

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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“…27 We and others have previously shown that glutamate increases in brain after cerebral ischemia in this permanent MCAO model [28][29][30] and that strategies that diminish extracellular glutamate levels could ameliorate the symptoms in rats. [31][32][33] In this context, glutamate uptake by glutamate transporters play a major role; specifically, EAAT2 or GLT1, that is predominantly located in astrocytes, has been reported to account for ≈95% of glutamate uptake in the adult central nervous system.…”

Section: Discussionmentioning

confidence: 82%

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

Hernández-Jiménez

Martínez-López

Gabandé‐Rodríguez

et al. 2016

Stroke

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Background and Purpose-3β-Hydroxysteroid-Δ24 reductase (DHCR24) or selective alzheimer disease indicator 1 (seladin-1), an enzyme of cholesterol biosynthetic pathway, has been implicated in neuroprotection, oxidative stress, and inflammation. However, its role in ischemic stroke remains unexplored. The aim of this study was to characterize the effect of seladin-1/DHCR24 using an experimental stroke model in mice. Methods-Dhcr24+/− and wild-type (WT) mice were subjected to permanent middle cerebral artery occlusion. In another set of experiments, WT mice were treated intraperitoneally either with vehicle or U18666A (seladin-1/DHCR24 inhibitor, 10 mg/kg) 30 minutes after middle cerebral artery occlusion. Brains were removed 48 h after middle cerebral artery occlusion for infarct volume determination. For protein expression determination, peri-infarct region was obtained 24 h after ischemia, and Western blot or cytometric bead array was performed. Results-Dhcr24+/− mice displayed larger infarct volumes after middle cerebral artery occlusion than their WT littermates. Treatment of WT mice with the seladin-1/DHCR24 inhibitor U18666A also increased ischemic lesion. Inflammationrelated mediators were increased after ischemia in Dhcr24 +/− mice compared with WT counterparts. Consistent with a role of cholesterol in proper function of glutamate transporter EAAT2 in membrane lipid rafts, we found a decreased association of EAAT2 with lipid rafts after ischemia when DHCR24 is genetically deleted or pharmacologically inhibited. Accordingly, treatment with U18666A decreases

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Intraischemic Hypothermia Decreases the Release of Glutamate in the Cores of Permanent Focal Cerebral Infarcts

Cited by 19 publications

References 59 publications

Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia

Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia

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

Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke

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