Neuroprotective Effect of Low-dose Lidocaine in a Rat Model of Transient Focal Cerebral Ischemia

2001 ◽  
Vol 95 (2) ◽  
pp. 445-451 ◽  
Author(s):  
Baiping Lei ◽  
James E. Cottrell ◽  
Ira S. Kass
Keyword(s):  
Weight Loss ◽  
Infarct Size ◽  
Low Dose ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Body Weight Loss ◽  
Neurologic Outcome ◽  
Triphenyltetrazolium Chloride ◽  
Lidocaine Group

Background A low concentration of lidocaine (10 microM) has been shown to reduce anoxic damage in vitro. The current study examined the effect of low-dose lidocaine on infarct size in rats when administered before transient focal cerebral isehemia. Methods Male Wistar rats (weight, 280-340 g) were anesthetized with isoflurane, intubated, and mechanically ventilated. After surgical preparation, animals were assigned to lidocaine 2-day (n = 10), vehicle 2-day (n 12), lidocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5-mg/kg bolus dose of ildocaine was injected intravenously 30 mm before isehemia in the lidocaine 2-day and 7-day groups. Thereafter, an infusion was initiated at a rate of 2 mg x kg(-1) x h(-1) until 60 min of reperfusion after isehemia. Rats were subjected to 90 min of focal cerebral isehemia using the intraluminal suture method. Infarct size was determined by image analysis of 2,3,5-triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin and eosin-stained sections 7 days after reperfusion. Neurologic outcome and body weight loss were also evaluated. Results The infarct size was significantly smaller in the lidocaine 2-day group (185.0+/-43.7 mm3) than in the vehicle 2-day group (261.3+/-45.8 mm3, P < 0.01). The reduction in the size of the infarct in the lidocaine 7-day group (130.4+/-62.9 mm3) was also significant compared with the vehicle 7-day group (216.6+/-73.6 mm3, P < 0.01). After 7 days of reperfusion, the rats in the lidocaine group demonstrated better neurologic outcomes and less weight loss. Conclusions The current study demonstrated that a clinical anriarrhythmic dose of lidocaine, when given before and during transient focal cerebral isehemia, significantly reduced infaret size, improved neurologic outcome, and inhibited postisehemic weight loss.

scholarly journals Therapeutic Activity of Intramuscular Peramivir in Mice Infected with a Recombinant Influenza A/WSN/33 (H1N1) Virus Containing the H275Y Neuraminidase Mutation

2012 ◽  
Vol 56 (8) ◽  
pp. 4375-4380 ◽  
Author(s):  
Yacine Abed ◽  
Andrés Pizzorno ◽  
Guy Boivin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Influenza A ◽  
Low Dose ◽  
Body Weight Loss ◽  
High Dose ◽  
Therapeutic Activity ◽  
Enzymatic Assays ◽  
Oseltamivir Resistance

ABSTRACTThe therapeutic activity of intramuscular (IM) peramivir was evaluated in mice infected with a recombinant influenza A/WSN/33 virus containing the H275Y neuraminidase (NA) mutation known to confer oseltamivir resistance. Regimens consisted of single (90 mg/kg of body weight) or multiple (45 mg/kg daily for 5 days) IM peramivir doses that were initiated 24 h or 48 h postinfection (p.i.). An oral oseltamivir regimen (1 or 10 mg/kg daily for 5 days) was used for comparison. Untreated animals had a mortality rate of 75% and showed a mean weight loss of 16.9% on day 5 p.i. When started at 24 h p.i., both peramivir regimens prevented mortality and significantly reduced weight loss (P< 0.001) and lung viral titers (LVT) (P< 0.001). A high dose (10 mg/kg) of oseltamivir initiated at 24 h p.i. also prevented mortality and significantly decreased weight loss (P< 0.05) and LVT (P< 0.001) compared to the untreated group results. In contrast, a low dose (1 mg/kg) of oseltamivir did not show any benefits. When started at 48 h p.i., both peramivir regimens prevented mortality and significantly reduced weight loss (P< 0.01) and LVT (P< 0.001) whereas low-dose or high-dose oseltamivir regimens had no effect on mortality rates, body weight loss, and LVT. Our results show that single-dose and multiple-dose IM peramivir regimens retain clinical and virological activities against the A/H1N1 H275Y variant despite some reduction in susceptibility when assessedin vitrousing enzymatic assays. IM peramivir could constitute an alternative for treatment of oseltamivir-resistant A/H1N1 infections, although additional studies are warranted to support such a recommendation.

Abstract W MP89: Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment after Experimental Focal Cerebral Ischemia

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Sahar Soliman ◽  
Tauheed Ishrat ◽  
Bindu Pillai ◽  
Adviye Ergul ◽  
Susan C Fagan
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Critical Role ◽  
Hemoglobin Content

Background & Objective: The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we tested the hypothesis that VEGF-B expression contributes to candesartan-mediated recovery. Methods: Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injection of lentiviral particles containing short hairpin RNA against VEGF-B (KD) or vehicle (NTC). Middle cerebral artery (MCA) was occluded for 90 minutes. At reperfusion, animals received either intravenous saline or candesartan. Neurobehavioral outcome was assessed 24, 48 and 72 hours after the insult and infarct size was measured at 72 hours. In an additional set of experiment, middle cerebral artery was occluded for 3h followed by 21h reperfusion. Rats were sacrificed at 24h post-MCAO and brains perfused for evaluation of vascular markers (edema and hemoglobin content). Results (Table): Candesartan-treated animals showed a significant reduction in the infarct size and edema accompanied by functional recovery in Bederson, beam walk, paw grasp and grip strength performance only in the presence of VEGF-B. In addition, candesartan-treated animals showed significantly reduction of hemoglobin content, a marker for hemorrhage and edema at 24 h after MCAO. Conclusion: Our results suggest VEGF-B plays a critical role in mediating candesartan’s neuronal and vascular protective effect after stroke. Identifying growth factors that mediate recovery after ischemic stroke presents possible targets for stroke therapeutics.

scholarly journals DJ-1 Protects against Neurodegeneration Caused by Focal Cerebral Ischemia and Reperfusion in Rats

2007 ◽  
Vol 28 (3) ◽  
pp. 563-578 ◽  
Author(s):  
Daijiro Yanagisawa ◽  
Yoshihisa Kitamura ◽  
Masatoshi Inden ◽  
Kazuyuki Takata ◽  
Takashi Taniguchi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia And Reperfusion

Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H2O2-mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.

Abstract 437: A Novel Variant Cell Cycle Related Kinase Protect Heart Against Ischemia by Promoting Cardiomyocytes Survival

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Lo Lai ◽  
Hongyu Qiu
Keyword(s):  
Cell Cycle ◽  
Infarct Size ◽  
Cardiac Myocytes ◽  
Mitogen Activated Protein Kinase ◽  
Adjacent Area ◽  
Potential Candidate ◽  
Triphenyltetrazolium Chloride ◽  
Novel Variant ◽  
Ischemic Stress

Background and objects: Our previous studies identified a novel variant of cell cycle-related kinase in heart (cardiac CCRK or cCCRK) which is different from generic CCRK found in other tissues in terms of its amino acid sequence, substrates, protein-protein interaction and tissue distribution. cCCRK has been found dramatically decreased in the failed heart tissues, while overexpress of cCCRK in cardiac myocytes in vitro protected the cells against induced cell death. Therefore, we tested the hypothesis here that cCCRK acts as a potential candidate of cell survival promotor providing cardiaoprotection in vivo upon cardiac ischemic stress. Methods and results: A cardiac specific transgenic (TG) mouse was generated with an alpha- MHC premotor in which cCCRK was overexpressed by 3.5 folds compared to wild type mice (WT). Both cCCRK TG and the litter-mated WT mice were subjected to an 45 minutes myocardial ischemia followed by an 24 hours reperfusion (IR), and the infarct size was measured by 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We found that despite the similar risk area, infarct size was significantly reduced by 50% in the TG mice verse WT mice (p<0.05). The apoptosis in the adjacent area of the heart tissues measured by TUNEL was reduced by 30% in TG mice vs WT (p<0.05). Mechanistically, the survival-promoting signaling pathway, including phosphorylated extracellular-signal-regulated kinase (p-ERK), phosphorylated Mitogen-activated protein kinase/ERK kinase (p-MEK), and P21, was activated in the heart tissues from TG vs WT mice (p<0.05 vs WT). Overexpression of cCCRK in cardiac myocytes in vitro reduced chelerythrine-induced apoptosis reflected by a reduction of caspase 3 activity, this protection was abolished by the Inhibition of MEK with the treatment of its inhibitor U1206 vs vehicle controls (p<0.05 vs vehicle). Conclusion: This study demonstrated that overexpression of a variant of CCRK in heart provides protection against ischemic stress by activating survival signaling.

scholarly journals The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3195
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Dae Hwan Yoon ◽  
Byung-Min Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Uncoupling Protein ◽  
Body Weight Loss ◽  
In Vivo Experiments ◽  
Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

scholarly journals 11β-Hydroxysteroid Dehydrogenase Type II Inhibition Causes Cerebrovascular Remodeling and Increases Infarct Size after Cerebral Ischemia

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 713-719 ◽  
Author(s):  
Jessica M. Osmond ◽  
Anne M. Dorrance
Keyword(s):  
Blood Pressure ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Hydroxysteroid Dehydrogenase ◽  
Enzyme Inactivation ◽  
Type Ii ◽  
Cerebral Vasculature ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Vessel

Direct mineralocorticoid receptor (MR) activation with deoxycorticosterone acetate has deleterious effects on the cerebral vasculature. Inhibition of 11β-hydroxysteroid dehydrogenase type II (11βHSD2) mimics the detrimental effects of elevated mineralocorticoids in the heart, but the effect of enzyme inactivation on the cerebral vasculature is unknown. Therefore, we hypothesized that systemic 11βHSD2 inhibition with carbenoxolone (CBX) would cause remodeling of the middle cerebral artery (MCA) and increase the damage caused by cerebral ischemia. Six-week-old male Sprague Dawley rats were divided into control and CBX (2.5 mg/d) + 0.9% NaCl treated. After 4 wk treatment, rats were used to assess either structure and reactivity of the MCA or the response to cerebral ischemia using the MCA occlusion technique. Cerebral damage was assessed by 2,3,5-triphenyltetrazolium chloride staining and expressed as a percentage of the hemisphere infarcted. CBX treatment increased systolic blood pressure (153.2 ± 7.3 vs. 122.1 ± 4.4 mm Hg; P &lt; 0.05) compared with control rats. MCAs from CBX treated rats were smaller and stiffer than control MCAs over a range of intralumenal pressures, indicating inward remodeling of the vessel. CBX treatment significantly increased ischemic cerebral infarct size compared with control rats (27.1 ± 5.4% vs. 14.8 ± 4.2%; P &lt; 0.05). These data indicate that inhibition of 11βHSD2, and, thus, disproportionate glucocorticoid activation of the MR, results in remodeling of the MCA and worsens the outcome of cerebral ischemia, further underscoring the importance of understanding the mechanism by which MR activation leads to cerebrovascular disease. 11β-Hydroxysteroid dehydrogenase inhibition increases blood pressure, altering cerebral vessel structure in a manner that increases the damaged caused by focal cerebral ischemia in rats.

IL-37: Novel neuroprotective effects after brain ischemia and reperfusion

2019 ◽  
Vol 7 (4) ◽  
pp. 310-321
Author(s):  
Huang Xiang ◽  
Stampf Wael
Keyword(s):  
Infarct Size ◽  
Brain Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Brain Inflammation ◽  
Mice Model ◽  
Triphenyltetrazolium Chloride ◽  
Nissl Staining ◽  
Neuroprotective Effects

Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. IL-37 (IL-37), a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. The purpose of the present study was to determine the effects of interleukin-37 on neuron cells and on brain inflammation induced by brain ischemia/reperfusion (I/R). A transgenic mouse strain was generated to express human IL-37 (hIL-37Tg) and WT mice were subjected to (60 min) brain ischemia and followed by reperfusion (24 h), by using a mice model of transient focal cerebral ischemia induced by advancing a nylon mono-filament to occlude the middle cerebral artery (MCA). Infarct size was determined by triphenyltetrazolium chloride staining. The morphology of neurons in brain sections were examined by Nissl staining and cytokines/chemokines measured by ELIZA. IL-37Tg significantly reduced infarct size by 65.4% (P<0.05) compared with WT after I/R. Reduced inflammation was associated with decreased leukocyte recruitment, and reduced release of IL-1β and TNFα, macrophage inflammatory protein-2 (MIP-2), MCP-1 and keratinocyte chemokine (KC) compared with WT (P<0.05), whereas IL-10 was increased eight fold (P<0.05). IL-37 significantly reduced cell death and increased Bcl-2 expression in neurons. Thus, IL-37 emerges as a key modulator of brain inflammation and has important translational implications for both the prevention and treatment of patients suffering from brain ischemia.

scholarly journals Neuroprotective Effect of Smilacis chinae Rhizome on NMDA-Induced Neurotoxicity In Vitro and Focal Cerebral Ischemia In Vivo

2008 ◽  
Vol 106 (1) ◽  
pp. 68-77 ◽  
Author(s):  
Ju Yeon Ban ◽  
Soon Ock Cho ◽  
Sun-Ha Choi ◽  
Hyun Soo Ju ◽  
Ju Yeon Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect

Rat and rabbit heart infarction: effects of anesthesia, perfusate, risk zone, and method of infarct sizing

1994 ◽  
Vol 267 (6) ◽  
pp. H2383-H2390 ◽  
Author(s):  
K. Ytrehus ◽  
Y. Liu ◽  
A. Tsuchida ◽  
T. Miura ◽  
G. S. Liu ◽  
...  
Keyword(s):  
Infarct Size ◽  
Regression Line ◽  
Rabbit Heart ◽  
Zone Size ◽  
Triphenyltetrazolium Chloride ◽  
Risk Zone ◽  
Heart Infarction ◽  
Rat Hearts ◽  
Experimental Variability

Rabbits and rats are becoming popular models for in vitro as well as in situ studies of myocardial infarction. In the present analysis we evaluated the results of several of our completed investigations and tested whether blood-free perfusate, anesthesia, or risk zone size affects infarction in these species. In addition, the influence of the method used for determining infarct size (histology or histochemistry) was examined in rabbits. All hearts experienced 30 min of regional ischemia followed by either 2-3 h of reperfusion in animals in which infarct size was assessed by staining with triphenyltetrazolium chloride or 72 h in those in which histological methods were used to measure infarct size. Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open-chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious rabbits were studied. Risk zone size measured with fluorescent particles was plotted against infarct size. Infarct size was linearly correlated with risk zone size and did not differ among models for each species. In rat hearts the regression line passed through the origin so that zero infarction occurred with zero risk zone size. However, in the rabbit heart there was no apparent infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk zone and infarction was found to be remarkably independent of the model chosen, the nonzero intercept for the rabbit heart can be an important, previously unrecognized source of experimental variability when infarct size is expressed as a percentage of the risk zone.

scholarly journals Active Compounds of Rhubarb Root and Rhizome in Animal Model Experiments of Focal Cerebral Ischemia

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Ai-ju Liu ◽  
Liang Song ◽  
Yan Li ◽  
Xiao-guang Zhang ◽  
Zi-xian Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Model Group ◽  
Active Compounds ◽  
Modern Times ◽  
Item Checklist ◽  
Included Article

Rhubarb root and rhizome (RRR) has been clinically used for stroke at least 2000 years and is still used in modern times in both China and elsewhere worldwide. The objective of present study was to evaluate the efficacy of active compounds of RRR (ACRRR) for experimental ischemic stroke. Studies of ACRRR in animal models of ischemic stroke were identified from 5 databases until April 2014. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit score and infarct size. All the data were analyzed using RevMan 5.1 software. As a result, 20 studies were identified describing procedures involving 577 animals. The quality score of studies ranges from 2 to 6, and the median was 3.4. Six studies showed significant effects of ACRRR for improving infarct size compared with model group (P<0.01). Six studies indicated significant effects of ACRRR for improving the neurological deficit scores according to Zea longa criterion or eight-point criterion (P<0.01). In conclusion, these findings demonstrated a possible efficacy of ACRRR that have potential neuroprotective effect for experimental ischemic stroke. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

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