scholarly journals A Selective N-Type Calcium Channel Antagonist Reduces Extracellular Glutamate Release and Infarct Volume in Focal Cerebral Ischemia

1995 ◽  
Vol 15 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Shunya Takizawa ◽  
Kazushi Matsushima ◽  
Hitoshi Fujita ◽  
Kazunori Nanri ◽  
Saori Ogawa ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Glutamate Release ◽  
Extracellular Glutamate ◽  
Neuroprotective Effects ◽  
Significant Difference ◽  
The Right

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-d-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 ± 15.8 μ M (mean ± SD) to 21.4 ± 11.4 μ M (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 ± 5.8 to 19.9 ± 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.

Effect of One Week Treatment with Ginkgo biloba Extract (EGb761) on Ischemia-Induced Infarct Volume in Gerbils

2003 ◽  
Vol 31 (04) ◽  
pp. 533-542 ◽  
Author(s):  
Shu-Ying Chung ◽  
Ming-Fu Wang ◽  
Jing-Ying Lin ◽  
Ming-Cheng Lin ◽  
Hui-Ming Liu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ginkgo Biloba ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Control Group ◽  
Tetrazolium Chloride ◽  
The Right

The present study was designed to evaluate the neuroprotective effects of Ginkgo biloba leaf extract (EGb761) in male gerbils subjected to focal cerebral ischemia produced by permanent occlusion of the right middle cerebral artery. In this study, gerbils were fed standard chow with or without EGb761 (100 mg/kg/day, i.g.) prior to cerebral ischemia for 1 week. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation. Infarct volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining 24 hours after initiation of cerebral ischemia. Results showed that the EGb761 group had significant reduction of infarct volume 4 and 6 mm from the frontal pole by 40% and 30%, respectively when compared to the control group ( p < 0.05). Mean locomotor activity of gerbils was reduced 24 hours after the occlusion of the MCA in both groups. However, there was no difference in locomotor activity between groups either 30 minutes before or 24 hours after the occlusion ( p < 0.05).

scholarly journals Sevoflurane Preconditioning against Focal Cerebral Ischemia

2009 ◽  
Vol 110 (6) ◽  
pp. 1271-1278 ◽  
Author(s):  
Jean-Laurent Codaccioni ◽  
Lionel J. Velly ◽  
Chahrazad Moubarik ◽  
Nicolas J. Bruder ◽  
Pascale S. Pisano ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Cerebral Injury ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Sprague Dawley ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Sevoflurane Preconditioning

Background Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n = 44) and preconditioned group (n = 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0 vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 = no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm(3)) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury.

scholarly journals Relationship between Extracellular Glutamate Concentration and Voltage-Sensitive Calcium Channel Function in Focal Cerebral Ischemia in the Rat

1996 ◽  
Vol 16 (4) ◽  
pp. 629-636 ◽  
Author(s):  
Hitoshi Osuga ◽  
Antoine M. Hakim
Keyword(s):  
Cerebral Ischemia ◽  
Calcium Channel ◽  
Focal Cerebral Ischemia ◽  
Focal Ischemia ◽  
Extracellular Glutamate ◽  
Molecular Responses ◽  
Control Value ◽  
Glutamate Concentration ◽  
Ischemic Depolarization

Ischemic cell death occurs when extracellular glutamate levels increase, causing tissue depolarization and an excessive rise in intracellular calcium concentrations. The relative occurrence of the depolarization events and the changes in glutamate concentration in ischemia have not been studied. In a model of focal cerebral ischemia in the rat, three measurements were made simultaneously in vivo: cerebral blood flow (CBF) by the H2-clearance method, extracellular glutamate concentration by microdialysis, and activation of the voltage-sensitive calcium channel (VSCC) by its binding to [3H]nimodipine. Effects of probe implantation on these measurements were accounted for. The CBF to control ratio obtained during the experiments spanned the range of 1.08 to 0.07. Binding to [3H]nimodipine became significantly activated when CBF fell to ∼0.49 of its control value while extracellular glutamate concentrations increased significantly only at a CBF ratio of <0.33. Activation of the VSCC at this high CBF ratio may be due to ischemic depolarization, which has been shown to activate the binding to [3H]nimodipine. It may be useful to define a CBF threshold of 50% of normal in focal ischemia for opening of the VSCC. The same threshold has been linked to an overall depression of protein synthesis and to activation of a number of molecular responses.

scholarly journals Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats

2018 ◽  
Vol 45 (2) ◽  
pp. 537-546 ◽  
Author(s):  
Yong Wang ◽  
Qianyao Ren ◽  
Xing Zhang ◽  
Huiling Lu ◽  
Jian Chen
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Brca1 Gene ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion ◽  
Tnf Α

Background/Aims: Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways. Methods: A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-α in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses. Results: The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-α significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-α. Conclusions: All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its anti-autophagic, anti-apoptotic and anti-inflammatory action.

scholarly journals Neuroprotective Effects of Inhibiting Poly(ADP-Ribose) Synthetase on Focal Cerebral Ischemia in Rats

1997 ◽  
Vol 17 (11) ◽  
pp. 1137-1142 ◽  
Author(s):  
Kazushi Takahashi ◽  
Joel H. Greenberg ◽  
Paul Jackson ◽  
Keith Maclin ◽  
Jie Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Substantial Reduction ◽  
Treated Group ◽  
Control Group ◽  
Triphenyltetrazolium Chloride ◽  
Neuroprotective Effects ◽  
Mca Occlusion

Poly(adenosine 5′-diphosphoribose) synthetase (PARS) has been described as an important candidate for mediation of neurotoxicity by nitric oxide. In the current study, we demonstrate for the first time that in vivo administration of a potent PARS inhibitor, 3,4-dihydro 5-[4-1(1-piperidinyl) butoxy]-1(2H)-isoquinolinone, leads to a significant reduction of infarct volume in a focal cerebral ischemia model in the rat. Focal cerebral ischemia was produced by cauterization of the right distal middle cerebral artery (MCA) with bilateral temporary common carotid artery occlusion for 90 minutes. 3,4-Dihydro 5[4-(1-piperidinyl) butoxy]-1(2H)-isoquinolinone was dissolved in dimethyl sulfoxide and injected intraperitoneally. Animals were treated 2 hours before MCA occlusion (control, n = 14; 5 mg/kg, n = 7; 10 mg/kg, n = 7; 20 mg/kg, n = 7; 40 mg/kg, n = 7), and 2 hours after MCA occlusion (same doses as before treatment). Twenty-four hours after MCA occlusion, the total infarct volume was measured using 2,3,5-triphenyltetrazolium chloride. Inhibition of PARS leads to a significant decrease in the damaged volume in the 5 mg/kg–treated group (106.7 ± 23.2 mm3; mean ± SD, P < 0.002), the 10 mg/kg–treated group (76.4 ± 16.8 mm3, P < 0.001), and the 20 mg/kg–treated group (110.2 ± 42.0 mm3, P < 0.02) compared with the control group (165.2 ± 34.0 mm3). The substantial reduction in infarct volume indicates that the activation of PARS may play an important role in the pathogenesis of brain damage in cerebral ischemia through intracellular energy depletion.

scholarly journals Neuroprotective Effects of the CRF1 Antagonist R121920 after Permanent Focal Ischemia in the Rat

2001 ◽  
Vol 21 (10) ◽  
pp. 1208-1214 ◽  
Author(s):  
Kenneth B. Mackay ◽  
Haig Bozigian ◽  
Dimitri E. Grigoriadis ◽  
Sarah A. Loddick ◽  
Gail Verge ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Experimental Models ◽  
Suture Technique ◽  
Bolus Administration ◽  
Neuroprotective Effects ◽  
Crf1 Antagonist ◽  
Hemispheric Infarct

The neuroprotective effects of a systemically active, highly selective, corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7-(dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a] pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia, where the middle cerebral artery (MCA) was occluded either through the subtemporal approach or using the intraluminal suture technique. R121920 rapidly crossed the blood–brain barrier after intravenous (IV) bolus administration (10 mg/kg), with peak brain concentrations at 5 minutes (2.26 ± 0.40 μg/mL), which were approximately 2-fold greater than those in plasma (0.98 ± 0.24 μg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg subcutaneously at hourly intervals for 4 hours) significantly ( P < 0.001) reduced total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal ischemia, significant reduction ( P < 0.05) in both outcome measures was obtained when R121920 administration was delayed up to 1 hour after MCAO. These results further define the antiischemic properties of selective CRF1 antagonists in two experimental models of permanent focal cerebral ischemia.

SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits

1997 ◽  
Vol 153 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Miguel A Perez-Pinzon ◽  
Midori A Yenari ◽  
Guo H Sun ◽  
David M Kunis ◽  
Gary K Steinberg
Keyword(s):  
Cerebral Ischemia ◽  
Calcium Channel ◽  
Calcium Channel Antagonist ◽  
Focal Cerebral Ischemia

scholarly journals Liraglutide Activates the Nrf2/HO-1 Antioxidant Pathway and Protects Brain Nerve Cells against Cerebral Ischemia in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Caihong Deng ◽  
Jun Cao ◽  
Jiangquan Han ◽  
Jianguo Li ◽  
Zhaohun Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Diabetic Rats ◽  
Neurological Deficits ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sprague Dawley ◽  
Significant Difference

This study aimed to determine the effect of liraglutide pretreatment and to elucidate the mechanism of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) signaling after focal cerebral ischemia injury in diabetic rats model. Adult male Sprague-Dawley rats were randomly divided into the sham-operated (S) group, diabetes mellitus ischemia (DM + MCAO) group, liraglutide pretreatment normal blood glucose ischemia (NDM+MCAO+L) group, and liraglutide pretreatment diabetes ischemia (DM + MCAO + L) group. At 48 h after middle cerebral artery occlusion (MCAO), neurological deficits and infarct volume of brain were measured. Oxidative stress brain tissue was determined by superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. The expression levels of Nrf2 and HO-1 of brain tissue were analyzed by western blotting. In the DM + MCAO + L group, neurological deficits scores and cerebral infarct volume seemed to decrease at 48 h after MCAO cerebral ischemia compared with those in DM + MCAO group (P<0.05). In addition, the expression of Nrf2 and HO-1 increased in 48 h at liraglutide pretreatment groups after MCAO cerebral ischemia if compared with those in the DM + MCAO group (P<0.05). Furthermore, the DM + MCAO + L group has no significant difference compared with the NDM + MCAO + L group (P>0.05). To sum up, alleviating effects of liraglutide on diabetes complicated with cerebral ischemia injury rats would be related to Nrf2/HO-1 signaling pathway.

Protective Effect of Vitamin E in a Rat Model of Focal Cerebral Ischemia

1998 ◽  
Vol 53 (3-4) ◽  
pp. 273-278 ◽  
Author(s):  
M. Stohrer ◽  
Andrea Eichinger ◽  
M. Schlachter ◽  
M. Stangassinger
Keyword(s):  
Vitamin E ◽  
Cerebral Ischemia ◽  
Rat Model ◽  
Oxygen Radicals ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Brain Infarction ◽  
Pathophysiological Mechanism ◽  
Cerebral Ischemia And Reperfusion ◽  
The Right

Abstract Under certain pathological conditions such as cerebral ischemia and reperfusion the occur­rence of free radicals is remarkably increased. However, only very little information is avail­ able on their quantitative relevance for the pathophysiology and final outcome of diseases. The aim of the present study was to evaluate the contribution of oxygen radicals in the pathogenesis of a stroke. For this purpose a rat model for stroke was used. Two of three vitamin E deficient groups were repleted with different dosages of DL-a-tocopherylacetate. N o signs of vitamin E deficiency could be observed. However, the weight gain during reple­tion was increased in the vitamin E repleted groups. Brain infarction was created by occlusion of the right middle cerebral artery (MCAO) for two hours. After 24 hours the measurements of infarct volumes were taken. The infarct volume of the group with the highest repletion dosage was significantly reduced by 81%. This was also expressed in a higher rate of gait disturbances after MCAO of the deficient animals. The control of vitamin E status exhibited a similar repletion-dependent level in plasma and brain. These results strongly support the hypothesis that the generation of oxygen radicals occurring during reperfusion is an impor­tant aspect of the pathophysiological mechanism in brain infarction.

scholarly journals Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hui Hu ◽  
Xiao ou Sun ◽  
Fang Tian ◽  
Hao Zhang ◽  
Qing Liu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Window ◽  
Vehicle Group ◽  
Neuroprotective Effects ◽  
Therapeutic Benefits ◽  
Neurobehavioral Deficits ◽  
Cerebral Artery Occlusion

Previous report has indicated that isosteviol has neuroprotective effects. However, isosteviol was administered preventively before ischemia and the inclusion criteria were limited. In the present study, a more soluble and injectable form of isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg·kg−1can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group. All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury.

Sign in / Sign up

Export Citation Format

Share Document