Cerebral ischemia/repefusion injury: From bench space to bedside

Nagy, Zoltán; Nardai, Sándor

doi:10.1016/j.brainresbull.2017.06.011

Cited by 58 publications

(38 citation statements)

References 113 publications

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“…The pathophysiological mechanism in stroke mainly involves excitotoxicity, altered energy metabolism, oxidative stress, inflammation and apoptosis . These mechanisms have been linked to altered brain metabolites qualitatively and quantitatively are now being the platform of interest in metabolomics.…”

Section: Discussionsupporting

confidence: 57%

“…Stroke is a second leading cause of death contributing to 11.8% of total deaths globally . Energy crisis because of stroke triggers a cascade of events involving excitotoxicity, mitochondrial dysfunction, elevated intracellular calcium levels and activation of apoptotic genes . Revascularisation with recombinant tissue plasminogen activator is the only available treatment option for stroke.…”

Section: Introductionmentioning

confidence: 99%

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1H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats

Gupta

Sharma

Jagannathan

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Stroke is a leading cause of death and disability worldwide with limited therapeutic interventions. The current study explored proton nuclear magnetic resonance spectroscopy ( 1 H NMR)-based metabolomic approach to elucidate the effect of lercanidipine on neurometabolic alterations in transient model of ischaemic stroke in rats. Methods In the present investigation, male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) for 2 h followed by reperfusion using intraluminal filament method. Rats were randomly divided into three groups as vehicle-treated sham control, vehicle-treated MCAo control and lercanidipine-treated MCAo. Vehicle or lercanidipine (0.5 mg/kg, i.p.) was administered 120 min post-reperfusion. The rat brain cortex tissues were isolated 24 h post-MCAo and were investigated by 1 H NMR spectroscopy through perchloric extraction method. Key findings A total of 23 metabolites were altered significantly after cerebral ischaemic-reperfusion injury in MCAo control as compared to sham control rats. Lercanidipine significantly reduced the levels of valine, alanine, lactate, acetate and tyrosine, while N-acetylaspartate, glutamate, glutamine, aspartate, creatine/phosphocreatine, choline, glycerophosphorylcholine, taurine, myo-inositol and adenosine di-phosphate were elevated as compared to MCAo control. Conclusions Present study illustrates effect of lercanidipine on neurometabolic alterations which might be mediated through its antioxidant, anti-inflammatory, vasodilatory and anti-apoptotic property in MCAo model of stroke.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

1H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats

Gupta

Sharma

Jagannathan

et al. 2020

Journal of Pharmacy and Pharmacology

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“…Stroke is a leading cause of disability in adults, resulting in social and economic burdens worldwide [81,82]. Numerous attempts [1,2,13,[83][84][85][86][87][88][89][90][91][92][93][94] have been made to reveal the pathological mechanisms underlying cerebral ischemia and to design new drugs [2,[95][96][97][98][99] that reduce the effects of complications due to stroke [100][101][102]. Because all of the pharmacological interventions that have been tested to date have failed, new targets for novel therapies are needed.…”

Section: Discussionmentioning

confidence: 99%

“…Ischemic stroke is the leading cause of brain dysfunction. However, because the mechanism of stroke pathogenesis has not been clarified to date, no effective medical treatments for reversing sensory, motor and cognitive impairments due to stroke have been devised [1,2]. Stroke is the second most prevalent cause of death and is the most common cause of permanent disability in adults [3].…”

Section: Introductionmentioning

confidence: 99%

Roles Played by the Na+/Ca2+ Exchanger and Hypothermia in the Prevention of Ischemia-Induced Carrier-Mediated Efflux of Catecholamines into the Extracellular Space: Implications for Stroke Therapy

et al. 2019

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The release of [ 3 H]dopamine ([ 3 H]DA) and [ 3 H]noradrenaline ([ 3 H]NA) in acutely perfused rat striatal and cortical slice preparations was measured at 37 °C and 17 °C under ischemic conditions. The ischemia was simulated by the removal of oxygen and glucose from the Krebs solution. At 37 °C, resting release rates in response to ischemia were increased; in contrast, at 17 °C, resting release rates were significantly reduced, or resting release was completely prevented. The removal of extracellular Ca 2+ further increased the release rates of [ 3 H]DA and [ 3 H]NA induced by ischemic conditions. This finding indicated that the Na + /Ca 2+ exchanger (NCX), working in reverse in the absence of extracellular Ca 2+ , fails to trigger the influx of Ca 2+ in exchange for Na + and fails to counteract ischemia by further increasing the intracellular Na + concentration ([Na + ] i ). KB-R7943, an inhibitor of NCX, significantly reduced the cytoplasmic resting release rate of catecholamines under ischemic conditions and under conditions where Ca 2+ was removed. Hypothermia inhibited the excessive release of [ 3 H] DA in response to ischemia, even in the absence of Ca 2+ . These findings further indicate that the NCX plays an important role in maintaining a high [Na + ] i , a condition that may lead to the reversal of monoamine transporter functions; this effect consequently leads to the excessive cytoplasmic tonic release of monoamines and the reversal of the NCX. Using HPLC combined with scintillation spectrometry, hypothermia, which enhances the stimulation-evoked release of DA, was found to inhibit the efflux of toxic DA metabolites, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL). In slices prepared from human cortical brain tissue removed during elective neurosurgery, the uptake and release values for [ 3 H]NA did not differ from those measured at 37 °C in slices that were previously maintained under hypoxic conditions at 8 °C for 20 h. This result indicates that hypothermia preserves the functions of the transport and release mechanisms, even under hypoxic conditions. Oxidative stress (H 2 O 2 ), a mediator of ischemic brain injury enhanced the striatal resting release of [ 3 H]DA and its toxic metabolites (DOPAL, quinone). The study supports our earlier findings that during ischemia transmitters are released from the cytoplasm. In addition, the major findings of this study that hypothermia of brain slice preparations prevents the extracellular calcium concentration ([Ca 2+ ] o )-independent non-vesicular transmitter release induced by ischemic insults, inhibiting Na + /Cl − -dependent membrane transport of monoamines and their toxic metabolites into the extracellular space, where they can exert toxic effects.

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“…A circulação sanguínea prejudicada produz uma série de efeitos complexos que influenciam os mecanismos apoptóticos (Nagy & Nardai, 2017) e aumentam a atividade da renina (Dong et al, 2011). Nossos resultados sugerem que não há relação importante entre diminuição ou inibição da expressão angII e apoptose celular nas regiões do corpo caloso e no córtex dorsal dos animais hidrocefálicos.…”

Section: Discussão | 69unclassified

O sistema renina-angiotensina como potencial alvo terapêutico na hidrocefalia experimental. Estudo comportamental, histológico e imunoistoquímico

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Cerebral ischemia/repefusion injury: From bench space to bedside

Cited by 58 publications

References 113 publications

1H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats

1H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats

Roles Played by the Na+/Ca2+ Exchanger and Hypothermia in the Prevention of Ischemia-Induced Carrier-Mediated Efflux of Catecholamines into the Extracellular Space: Implications for Stroke Therapy

O sistema renina-angiotensina como potencial alvo terapêutico na hidrocefalia experimental. Estudo comportamental, histológico e imunoistoquímico

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