Mitochondrial function and cerebral blood flow variable responses to middle cerebral artery occlusion

Livnat, Amir; Barbiro-Michaely, Efrat; Mayevsky, Avraham

doi:10.1016/j.jneumeth.2010.01.022

Cited by 10 publications

(3 citation statements)

References 39 publications

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“…Ischemia-induced cerebral injury leads to cerebral infarction and, ultimately, brain dysfunction (16,17). In the present study, it was observed that ischemia exacerbated neurological deficits and increased cerebral infarction.…”

Section: Discussionsupporting

confidence: 54%

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

Sun

et al. 2017

Mol Med Report

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The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low‑myricetin (1 mg/kg), medium‑myricetin (5 mg/kg) and high‑myricetin (25 mg/kg) groups. Neurological deficit scores were evaluated by an examiner blinded to the experimental groups. Brain infarct size was estimated macroscopically using 2,3,5‑triphenyltetrazolium chloride staining. The levels of inflammatory factors tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β, and oxidative stress index superoxide dismutase (SOD), malondiadehyde (MDA), and the glutathione/glutathione disulfide (GSH/GSSG) ratio were measured by ELISA. The degree of brain cell apoptosis was determined using a terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. Protein expression levels of total or phosphorylated p38 mitogen activated protein kinase (MAPK), nuclear factor (NF)‑κB/p65 and protein kinase B (AKT) were determined using a western blotting assay. The neurological deficit score and infarct area induced by pMCAO decreased in a dose‑dependent manner following myricetin treatment. Furthermore, myricetin reduced the expression levels of IL‑1β, IL‑6, TNF‑α, and MDA, and increased GSH/GSSG ratio and SOD activity. A significant decrease in cell apoptosis was observed in response to myricetin. In addition, myricetin significantly increased the level of phosphorylated AKT protein, and decreased the phosphorylation of p38 MAPK and the level of NF‑κB/p65. Overall, the results of the present study suggested that myricetin exhibits a therapeutic effect by reducing ischemic cerebral injury, and the protective effect of myricetin may be associated with the p38 MAPK, NF‑κB/p65 and AKT signaling pathways.

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Section: Discussionsupporting

confidence: 54%

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

Sun

et al. 2017

Mol Med Report

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“…Variability in infarct volume or functional outcome attributable to these concerns could decrease reliability of this model. There are methods for confirmation of ischemia during intraluminal MCAO including positron emission tomography (Martin et al, 2012), magnetic resonance imaging (Bihel et al, 2010), laser speckle imaging (Akamatsu et al, 2012), hydrogen clearance (Laing et al, 1993), and fluorometric measurement of mitochondrial NADH (Livnat et al, 2010). While these monitors have important roles in certain experimental paradigms, LDF has been advocated because the LDF system is compact, easy to use, and does not require complex surgery or radionuclide use.…”

Section: Discussionmentioning

confidence: 99%

A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat

Taninishi

Jung

Izutsu

et al. 2015

Journal of Neuroscience Methods

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“…The impact of ischemia -to some degree-can be described by neurological deficits using neurological severit y assessment scores (Bederson, Pitts et al 1986, Garcia, Wagner et al 1995 or behavioral tests (Schallert 2006, Encarnacion, Horie et al 2011). However, one major drawback of the intraluminal method is the occurrence of model-immanent confounding pathologies and complications: incomplete MCAO (Zausinger, Baethmann et al 2002), early, late or missing reperfusion (Livnat, Barbiro-Michaely et al 2010), and subarachnoid hemorrhage (Longa, Weinstein et al 1989, Schmid-Elsaesser, Zausinger et al 1998. Particularly with regard to time-and labour-consuming long-term experiments a reliable and prompt surveillance of the desired vessel occlusion excluding any secondary damages is of great importance because MRI is not always available or feasible and the additional lesions at the time of sacrifice may no longer be recognizable and therefore results may be biased.…”

Section: Introductionmentioning

confidence: 99%

Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke

Liebenstund

Coburn

Fitzner

et al. 2020

Disease Models &Amp; Mechanisms

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The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies).The tMCAO monitoring data (bilateral cerebral blood flow - CBF, heart rate - HR, mean arterial pressure - MAP) of 16 animals with an “ideal” outcome (MCA-ischemia) and 48 animals with additional or other pathologies (subdural hematoma or subarachnoid hemorrhage) were checked for their prognostic performance (receiver operating characteristic curve and area under the curve - AUC).Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP in addition to baseline HR (AUC 0.83, 95% CI 0.68 to 0.97) increased prognostic relevance (AUC 0.89, 95% CI 0.79 to 0.98). Prediction performance improved when two additional predictors referring differences in left and right CBF were considered (AUC 1.00, 95% CI 1.0 to 1.0).Our data underline the importance of periinterventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

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Mitochondrial function and cerebral blood flow variable responses to middle cerebral artery occlusion

Cited by 10 publications

References 39 publications

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

Myricetin against ischemic cerebral injury in rat middle cerebral artery occlusion model

A blinded randomized assessment of laser Doppler flowmetry efficacy in standardizing outcome from intraluminal filament MCAO in the rat

Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke

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