Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1085-1093 ◽  
Author(s):  
E-Jian Lee ◽  
Ming-Yang Lee ◽  
Guan-Liang Chang ◽  
Li-Hsuan Chen ◽  
Yu-Ling Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Content Type ◽  
Delayed Treatment ◽  
Cerebral Ischemia Reperfusion ◽  
Fine Print

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion. Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died. Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively. Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.

scholarly journals Electroacupuncture Could Regulate the NF-κB Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Wen-yi Qin ◽  
Yong Luo ◽  
Ling Chen ◽  
Tao Tao ◽  
Yang Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Inflammatory Injury ◽  
Cerebral Ischemia Reperfusion

The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF-κB signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1βand IL-13 were detected. NF-κB p65, IκBα, IKKα, and IKKβwere analyzed and the ability of NF-κB binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1βand IL-13. The treatment reduced the expression of IKKαand IKKβand altered the expression of NF-κB p65 and IκBαin the cytoplasm and nucleus; the activity of NF-κB was effectively reduced. We conclude that EA treatment might interfere with the process of NF-κB nuclear translocation. And it also could suppress the activity of NF-κB signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion.

scholarly journals Hemorrhagic Transformation and Microvascular Integrity during Focal Cerebral Ischemia/Reperfusion

1996 ◽  
Vol 16 (6) ◽  
pp. 1373-1378 ◽  
Author(s):  
Gerhard F. Hamann ◽  
Yasushi Okada ◽  
Gregory J. del Zoppo
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Hemorrhagic Transformation ◽  
Artery Occlusion ◽  
Time Dependent ◽  
Adolescent Male ◽  
Blood Components ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Artery Occlusion

Hemorrhagic transformation after cerebral ischemia is a well known clinical concern. The frequency of intact basal lamina (BL), identified by laminin antigen, in hemorrhagic and nonhemorrhagic zones after middle cerebral artery occlusion (MCA:O) and 3-h MCA:O with reperfusion in adolescent male baboons was assessed. Parenchymal hemoglobin was not detected prior to 24-h reperfusion. A significant decrease in the density of laminin (BL) in hemorrhagic zones (6.2 ± 2.4) compared with nonhemorrhagic ischemic zones (10.5 ± 2.4) (p < 0.05) and nonischemic basal ganglia (17.0 ± 2.7) (p < 0.01) was observed. Time-dependent changes in BL integrity appear linked to the extravasation of blood components.

scholarly journals Guhong Injection Alleviates Cerebral Ischemia–Reperfusion Injury via the PKC/HIF-1α Pathway in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Yu ◽  
Yangyang Zhang ◽  
Xixi Zhao ◽  
Haitong Wan ◽  
Yu He ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Positive Control ◽  
Artery Occlusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion

Guhong injection (GHI) is a drug for ischemic stroke created by combining safflower, a traditional Chinese medicine, and aceglutamide, a Western medicine. In this study, we investigated the curative effect of GHI on cerebral ischemia–reperfusion (I/R) injury via the PKC/HIF-1α pathway in rats. Adult male Sprague Dawley rats were randomly divided into seven groups: sham-operated, middle cerebral artery occlusion (MCAO), GHI, nimodipine injection (NMDP), MCAO + LY317615 (PKC inhibitor), GHI + LY317615, and NMDP + LY317615. After establishing an MCAO rat model, we performed neurological deficit testing, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay, Western blotting, and q-PCR to detect the brain damage in rats. Compared with the MCAO group, the GHI and GHI + LY317615 group showed neurological damage amelioration as well as decreases in serum hypoxia-inducible factor-1α (HIF-1α), protein kinase C (PKC), and erythropoietin levels; brain HIF-1α and inducible nitric oxide synthase protein expression; and brain HIF-1α and NOX-4 mRNA expression. These effects were similar to those in the positive control groups NMDP and NMDP + LY317615. Thus, our results confirmed GHI can ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway.

scholarly journals Electroacupuncture Pretreatment against Cerebral Ischemia/Reperfusion Injury through Mitophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Chenlu Mao ◽  
Cheng Hu ◽  
Yudi Zhou ◽  
Rong Zou ◽  
Sha Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Volume Number ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Artery Occlusion

Cerebral ischemia/reperfusion (I/R) injury can induce the mitophagy of neurons in the ischemic brain. Electroacupuncture (EA) pretreatment has a protective effect on cerebral ischemia/reperfusion injury. However, its internal mechanism still needs to be further studied. The present study’s purpose is to investigate whether mitophagy is involved in neuroprotection elicited by EA pretreatment in a rat model of cerebral ischemia/reperfusion injury. The rats were pretreated with vehicle, EA at the Baihui (GV20) and Shuigou (GV26) acupoints 30 min daily, for 5 days consecutively prior to the focal cerebral ischemia injury induced by the middle cerebral artery occlusion (MCAO) model. Compared to the sham group, the neurological scores, infarction volume, number of autophagosomes, FUNDC1, p62, and the ratio of LC3-II/I were significantly increased but mitochondrial membrane potential and autophagy-related protein p-mTORC1 significantly decreased in the I/R group. However, EA pretreatment significantly reversed these trends. Overall, the results of this study demonstrated that EA pretreatment protected the cerebral ischemia/reperfusion injury which maybe correlated with mitophagy.

Neuroprotective effect of peroxynitrite decomposition catalyst and poly(adenosine diphosphate—ribose) polymerase inhibitor alone and in combination in rats with focal ischemia

2004 ◽  
Vol 101 (4) ◽  
pp. 669-675 ◽  
Author(s):  
Shyam S. Sharma ◽  
Shankar Munusamy ◽  
Meenakshisundaram Thiyagarajan ◽  
Chaman L. Kaul
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Parp Inhibitor ◽  
Adenosine Diphosphate ◽  
Neurological Deficits ◽  
Content Type ◽  
Fine Print

Object. The authors evaluated the neuroprotective effect of 5,10,15,20-tetrakis(N-methyl-4′-pyridyl)porphyrinatoiron(III) (FeTMPyP), a peroxynitrite decomposition catalyst, and 1,5-isoquinolinediol (ISO), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, alone and in combination in rats with focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Methods. Male Sprague—Dawley rats were subjected to 2 hours of MCAO followed by 22 hours of reperfusion. Cerebral infarction and neurological deficits were estimated after ischemia. Intraperitoneal injections of FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) were administered alone or in combination in ischemic animals. The PARP activity in vehicle- and drug-treated groups was estimated using anti—poly(ADP-ribose) antibody in immunofluorescence and immunoblotting studies. Two hours of MCAO and 22 hours of reperfusion produced significant cerebral infarction and neurological deficits. Treatment with FeTMPyP (1 and 2 mg/kg) and ISO (0.05 and 0.1 mg/kg) produced a significant reduction in cerebral infarction and neurological deficits. Combination therapy (2 mg/kg FeTMPyP and 0.1 mg/kg ISO) enhanced the inhibition of ischemic volume (77.81 ± 0.86%) compared with monotherapies (FeTMPyP 54.07 ± 5.6% and ISO 53.06 ± 3.88%). Immunoblotting and immunofluorescence studies showed PARP activation after ischemia, which was reduced by drug treatment. Conclusions. Neuroprotection observed with FeTMPyP and ISO alone and in combination may be attributed to inhibition of the peroxynitrite—PARP cascade of cerebral ischemia/reperfusion injury.

scholarly journals A20-Binding Inhibitor of NF-κB 1 Ameliorates Neuroinflammation and Mediates Antineuroinflammatory Effect of Electroacupuncture in Cerebral Ischemia/Reperfusion Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xueling Zhou ◽  
Wenhao Lu ◽  
You Wang ◽  
Jiani Li ◽  
Yong Luo
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Cerebral Ischemia Reperfusion ◽  
Neuroprotective Strategy

A20-binding inhibitor of NF-κB 1 (ABIN1) is an inhibitor of NF-κB and exerts anti-inflammatory effect. Electroacupuncture (EA) is considered as a neuroprotective strategy by inhibiting neuroinflammatory damage after cerebral ischemia. This study was performed to explore the role of ABIN1 and investigate whether the ABIN1 is involved in the mechanism of EA in cerebral ischemia/reperfusion (I/R) rats. Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and received EA after reperfusion once a day. Lentivirus-mediated ABIN1 gene knockdown was used to detect the role of ABIN1 in neuroinflammation after I/R. ABIN1 expression, proinflammatory cytokine levels, microglial activation, neurological function, infarct volumes, and NF-κB activation were assessed. ABIN1 expression was elevated in the peri-infarct cortex and was further upregulated by EA. ABIN1 knockdown increased the levels of proinflammatory cytokines and activation of microglia, worsened neurological deficits, and enlarged the infarct volume. Moreover, ABIN1 was blocked to partially reverse the neuroprotective effect of EA, and this treatment weakened the ability of EA to suppress NF-κB activity. Based on these findings, ABIN1 is a potential suppressor of neuroinflammation and ABIN1 mediates the antineuroinflammatory effect of EA in cerebral I/R rats.

scholarly journals Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094619
Author(s):  
Liru Li ◽  
Jie Huang
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion ◽  
Y Maze

Although rapamycin can attenuate cerebral ischemia/reperfusion (I/R) injury, the potential roles of rapamycin on cerebral I/R injury remain largely controversial. The present work aims to evaluate underlying molecular mechanisms of rapamycin pretreatment on I/R injury. In total, 34 Sprague-Dawley rats were randomly grouped to 3 groups: sham group (n = 2), vehicle group (n = 16), and rapamycin-pretreatment group (n = 16). Before the focal cerebral ischemia was induced, those rats in the pretreatment group were intraperitoneally injected rapamycin (1 mg/kg body) for 20 hours, while rats in the vehicle group received same-volume saline. Then, rats in these 2 groups received focal cerebral ischemia for 3 and 6 hours, respectively (n = 8 in each group), which was followed by the application of reperfusion for 4, 24, 72 hours, and 1 week (n = 2 in each group). The results showed that the rapamycin pretreatment improved the memory functions of rats after I/R injury, which was evaluated using a Y-maze test. Rapamycin pretreatment significantly reduced the size of triphenyltetrazolium chloride infarction and decreased the expression of I/R injury markers. Moreover, the expression of LC-3 and NFκB was also significantly reduced after rapamycin pretreatment. Taken together, rapamycin pretreatment may alleviate cerebral I/R injury partly through inhibiting autophagic activities and NFκB pathways in rats.

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.

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