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 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.

Role of a synthetic pyrimidine compound, MS-818, in reduction of infarct size and amelioration of sensorimotor dysfunction following permanent focal cerebral ischemia in rats

2002 ◽  
Vol 96 (6) ◽  
pp. 1072-1076 ◽  
Author(s):  
Tetsuryu Mitsuyama ◽  
Takakazu Kawamata ◽  
Fumitaka Yamane ◽  
Akira Awaya ◽  
Tomokatsu Hori
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Biological Activities ◽  
Infarct Volume ◽  
Saline Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Content Type ◽  
Fine Print

Object. A synthetic heterocyclic pyrimidine compound, MS-818 (2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is reported to have a variety of biological activities including neurite outgrowth, astrocyte differentiation, suppression of neuronal apoptosis, regeneration of injured peripheral nerves, fracture repairs, angiogenesis, and superovulation. To be able to explicate the neurotrophic effects of MS-818, the authors evaluated its effect on the reduction of infarct volume and amelioration of sensorimotor dysfunction in a rat model of focal ischemia. Methods. Forty male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion and assigned to one of four treatment groups (10 animals in each group). The MS-818 (1, 5, or 10 mg/kg) or phosphate-buffered saline (control group) was administered intraperitoneally at onset of ischemia and again 24 hours later. The rats were killed 48 hours after they underwent surgery to induce stroke, and infarct volume was determined using an image-analysis computer software program following staining with 2,3,5-triphenyltetrazolium chloride. Postischemic neurological deficit and body weight were also assessed. Conclusions. Significant reductions in infarct volume (total and cortical infarction) were found in all the MS-818—treated groups compared with the control group. Furthermore, MS-818 induced significant amelioration of sensorimotor dysfunction, as indicated by the results of forelimb and hindlimb placing tests. The present findings suggest that MS-818, which has a much smaller molecular weight than neurotrophic peptides, represents a new approach to the treatment of focal cerebral ischemia.

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 Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

2018 ◽  
Vol 125 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Chun Li ◽  
Hong Sun ◽  
Guodong Xu ◽  
Kimberly D. McCarter ◽  
Jiyu Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Ischemic Brain Damage ◽  
Mitochondrial Oxidative Stress ◽  
Ischemic Brain

Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg−1·day−1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg−1·day−1ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloproteinase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation.NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

scholarly journals Effect of combined therapy with hyperbaric oxygen and an antioxidant on infarct volume after permanent focal cerebral ischemia

2007 ◽  
pp. 369-373
Author(s):  
G Acka ◽  
A Sen ◽  
Z Canakci ◽  
S Yildiz ◽  
A Akin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Hyperbaric Oxygen ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Combined Therapy ◽  
Artery Occlusion ◽  
Control Group ◽  
Male Wistar Rats ◽  
Cerebral Artery Occlusion ◽  
Reduce Infarct Volume

The aim of the present study was to evaluate the efficiency of combination of hyperbaric oxygen (HBO) and an antioxidant on permanent focal cerebral ischemia. Male Wistar rats underwent permanent middle cerebral artery occlusion (MCAO). Then, animals were randomly assigned to one of four groups: the control group (n=9) received no treatment, HBO group (n=9) was treated for 90 min at 2.5 absolute atmosphere for 3 days, the U-74389G group (n=8) received single U-74389G injection (3 mg/kg), the HBO + U-74389G group (n=8) received both HBO and U-74389G treatments. Treatments were initiated within the first 10 min after MCAO. After 3 days, the infarct volumes in rat brains were measured. The infarct ratios were 25.6+/-6.5 % for the control group, 21.9+/-6.4 % for the HBO group, 15.7+/-5.7 % for U-74389G group and 12.5+/-3.8 % for HBO + U74389G group. The infarct volumes were significantly reduced in rats treated with U-74389G (p<0.05) and combination therapy (p<0.05). HBO failed to reduce infarct volume significantly. We concluded that 1) U-74389G is more beneficial than HBO on permanent MCAO in rats, and 2) a combined therapy failed to significantly improve infarct volume more than either single treatment.

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 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.

scholarly journals Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

1995 ◽  
Vol 15 (6) ◽  
pp. 953-959 ◽  
Author(s):  
Marc Fisher ◽  
Mary-Ellen Meadows ◽  
Tuyen Do ◽  
Jens Weise ◽  
Vladimir Trubetskoy ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Focal Cerebral Ischemia ◽  
Brain Temperature ◽  
Infarct Volume ◽  
Fibroblast Growth ◽  
Sprague Dawley ◽  
Arterial Blood

Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 μg/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague–Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 ± 1.0 in vehicle-treated and 1.5 ± 1.3 in bFGF-treated rats (mean ± SD; TV = 12 vs. 11; p = 0.009). Infarct volume was 297 ± 65 mm3 in vehicle- and 143 ± 135 mm3 in bFGF-treated animals ( p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood–brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

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