scholarly journals Ornithine Decarboxylase Knockdown Exacerbates Transient Focal Cerebral Ischemia-Induced Neuronal Damage in Rat Brain

2001 ◽  
Vol 21 (8) ◽  
pp. 945-954 ◽  
Author(s):  
Raghavendra Vemuganti L. Rao ◽  
Aclan Dogan ◽  
Kellie K. Bowen ◽  
Robert J. Dempsey
Keyword(s):  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Motor Deficits ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Transient Focal Cerebral Ischemia

Transient cerebral ischemia leads to increased expression of ornithine decarboxylase (ODC). Contradicting studies attributed neuroprotective and neurotoxic roles to ODC after ischemia. Using antisense oligonucleotides (ODNs), the current study evaluated the functional role of ODC in the process of neuronal damage after transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats. Transient MCAO significantly increased the ODC immunoreactive protein levels and catalytic activity in the ipsilateral cortex, which were completely prevented by the infusion of antisense ODN specific for ODC. Transient MCAO in rats infused with ODC antisense ODN increased the infarct volume, motor deficits, and mortality compared with the sense or random ODN-infused controls. Results of the current study support a neuroprotective or recovery role, or both, for ODC after transient focal ischemia.

scholarly journals Lack of Neuroprotection of Inhibitory Peptides Targeting Jun/JNK after Transient Focal Cerebral Ischemia in Spontaneously Hypertensive Rats

2011 ◽  
Vol 31 (12) ◽  
pp. e1-e8 ◽  
Author(s):  
William R Gow ◽  
Kym Campbell ◽  
Amanda J Meade ◽  
Paul M Watt ◽  
Nadia Milech ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Receptor Activation ◽  
Glutamate Excitotoxicity ◽  
Functional Score ◽  
Adhesive Tape ◽  
Tat Peptide ◽  
Spontaneously Hypertensive ◽  
Transient Focal Cerebral Ischemia

In this study, we have assessed the ability of two TAT-fused peptides PYC36d-TAT and JNKI-1d-TAT (JNKI-1 or XG-102), which respectively inhibit jun proto-oncogene (c-Jun) and c-Jun N-terminal kinase (JNK) activation, to reduce infarct volume and improve functional outcome (adhesive tape removal) after transient focal cerebral ischemia in Spontaneously Hypertensive (SH) rats. PYC36d-TAT and JNKI-1d-TAT peptide batches used for experiments were tested in vitro and protected cortical neurons against glutamate excitotoxicity. Rats were treated intravenously with three different doses of PYC36d-TAT (7.7, 76, or 255 nmol/kg), JNKI-1d-TAT (255 nmol/kg), d-TAT peptide (255 nmol/kg), or saline (vehicle control), 10 minutes after reperfusion after 90 minutes of middle cerebral artery occlusion (MCAO). Contrary to other stroke models, no treatment significantly reduced infarct volume or improved functional score measurements compared with vehicle-treated animals when assessed 48 hours after MCAO. Additionally, assessment of the JNKI-1d-TAT peptide, when administered 1 or 2 hours after reperfusion after 90 minutes of MCAO, also did not improve histological or functional outcomes at 48 hours after occlusion. This study is the first to evaluate the efficacy of PYC36d-TAT and JNKI-1d-TAT using the SH rat, which has recently been shown to be more sensitive to AMPA receptor activation rather than to NMDA receptor activation after cerebral ischemia, and which may have contributed to the negative findings.

scholarly journals Acute Treatment with Rosuvastatin Protects Insulin Resistant (C57BL/6J ob/ob) Mice against Transient Cerebral Ischemia

2008 ◽  
Vol 28 (12) ◽  
pp. 1927-1935 ◽  
Author(s):  
Keita Mayanagi ◽  
Prasad V Katakam ◽  
Tamas Gáspár ◽  
Ferenc Domoki ◽  
David W Busija
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Blood Cholesterol ◽  
Doppler Flowmetry ◽  
Insulin Resistant ◽  
Transient Focal Cerebral Ischemia ◽  
Intracellular Adhesion Molecule ◽  
Cerebral Artery Occlusion

The purpose of this study was to investigate the short-term effects of rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on transient, focal cerebral ischemia in C57BL/6J ob/ob mice with insulin resistance (IR). Male ob/ob, lean, or wild-type (WT) mice were treated with RSV (10 mg/kg per day, i.p.) or vehicle for 3 days. Ischemia was induced by 60 mins of middle cerebral artery occlusion (MCAO) and cortical blood flow (CBF) was monitored by laser-Doppler flowmetry. Infarct volumes were measured 24 h after reperfusion. IR mice exhibited a higher infarct volume compared with Lean or WT mice, and RSV reduced infarct volume only in obese mice (40% ± 3% versus 32% ± 3%, P < 0.05). Blood cholesterol and insulin levels were elevated in ob/ob mice but were unaffected by RSV. The CBF reductions during MCAO were similar in all groups and were not affected by RSV. Although RSV did not increase cortical endothelial NO synthase (eNOS) levels in the ob/ob mice, it attenuated the increased cortical expression of intracellular adhesion molecule-1 (ICAM-1) after MCAO from ob/ob mice. Thus, RSV protects against stroke in IR mice by a mechanism independent of effects on the lipid profile, CBF, or eNOS but dependent on suppression of post-MCAO ICAM-1 expression.

scholarly journals Effects of Pretreatment with a Combination of Melatonin and Electroacupuncture in a Rat Model of Transient Focal Cerebral Ischemia

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Lingguang Liu ◽  
R. T. F. Cheung
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Brain Infarct ◽  
Beneficial Effects ◽  
Transient Focal Cerebral Ischemia ◽  
Cerebral Artery Occlusion

Both melatonin and electroacupuncture (EA) have been suggested to be effective treatments against stroke. However, it is unknown whether a combination of these two therapies could be beneficial against transient focal cerebral ischemia. The present study investigated the effects of pretreatment of a combination of melatonin and EA in a rat model of transient middle cerebral artery occlusion (MCAO). After pretreatment of melatonin plus EA (MEA), transient MCAO was induced for 90 minutes in male Sprague-Dawley (SD) rats. The neurological deficit score, brain infarct volume, cerebral edema ratio, neuronal inflammation, and apoptosis were evaluated 24 hours after transient MCAO. The expression of related inflammatory and apoptotic mediators in the brain was also investigated. The results showed that MEA improved neurological outcome, reduced brain infarct volume, and inhibited neuronal inflammation as well as apoptosis 24 hours after transient MCAO. The beneficial effects may derive from downregulation of proinflammatory and proapoptotic mediators and upregulation of antiapoptotic mediators. Thus, these results suggest a preventive effect of pretreatment of MEA on transient focal cerebral ischemia.

scholarly journals Temperature Modulation of Cerebral Depolarization during Focal Cerebral Ischemia in Rats: Correlation with Ischemic Injury

1993 ◽  
Vol 13 (3) ◽  
pp. 389-394 ◽  
Author(s):  
Qun Chen ◽  
Michael Chopp ◽  
Gordon Bodzin ◽  
Hua Chen
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Cell Damage ◽  
Infarct Volume ◽  
Cortical Lesion ◽  
Temperature Modulation ◽  
Ischemic Infarct ◽  
Dc Potential ◽  
Ischemic Depolarization

The role of cerebral depolarizations in focal cerebral ischemia is unknown. We therefore measured the direct current (DC) electrical activity in the cortex of Wistar rats subjected to transient occlusion of the middle cerebral artery (MCA). Focal ischemia was induced for 90 min by insertion of an intraluminal filament to occlude the MCA. To modulate cell damage, we subjected the rats to hypothermic (30°C, n = 4), normothermic (37°C, n = 4), and hyperthermic (40°C, n = 6) ischemia. Controlled temperatures were also maintained during 1 h of reperfusion. Continuous cortical DC potential changes were measured using two active Ag–AgCl electrodes placed in the cortical lesion. Animals were killed 1 week after ischemia. The brains were sectioned and stained with hematoxylin and eosin, for evaluation of neuronal damage, and calculation of infarct volume. All animals exhibited an initial depolarization within 30 min of ischemia, followed by a single depolarization event in hypothermic animals, and multiple periodic depolarization events in both normothermic and hyperthermic animals. Hyperthermic animals exhibited significantly more (p < 0.05) DC potential deflections (n = 6.17 ± 0.67) than normothermic animals (n = 2.75 ± 0.96). The ischemic infarct volume (% of hemisphere) was significantly different for the various groups; hypothermic animals exhibited no measurable infarct volume, while the ischemic infarct volume was 10.2 ± 12.3% in normothermic animals and 36.5 ± 3.4% in hyperthermic animals (p < 0.05). A significant correlation was detected between the volume of infarct and number of depolarization events ( r = 0.90, p < 0.001). Our data indicate that body temperature has a profound effect on the number of ischemic depolarization events, and ischemic cell damage after transient MCA occlusion, and suggest a role for ischemic depolarizations in mediating ischemic cell damage.

scholarly journals Transcriptomic characterization of microglia activation in a rat model of ischemic stroke

2020 ◽  
Vol 40 (1_suppl) ◽  
pp. S34-S48
Author(s):  
Wenjun Deng ◽  
Emiri Mandeville ◽  
Yasukazu Terasaki ◽  
Wenlu Li ◽  
Julie Holder ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Phenotypic Diversity ◽  
Focal Cerebral Ischemia ◽  
Wide Spectrum ◽  
Spontaneously Hypertensive ◽  
Transient Focal Cerebral Ischemia ◽  
Microglial Response ◽  
Whole Transcriptome

Microglia are key regulators of inflammatory response after stroke and brain injury. To better understand activation of microglia as well as their phenotypic diversity after ischemic stroke, we profiled the transcriptome of microglia after 75 min transient focal cerebral ischemia in 3-month- and 12-month-old male spontaneously hypertensive rats. Microglia were isolated from the brains by FACS sorting on days 3 and 14 after cerebral ischemia. GeneChip Rat 1.0ST microarray was used to profile the whole transcriptome of sorted microglia. We identified an evolving and complex pattern of activation from 3 to 14 days after stroke onset. M2-like patterns were extensively and persistently upregulated over time. M1-like patterns were only mildly upregulated, mostly at day 14. Younger 3-month-old brains showed a larger microglial response in both pro- and anti-inflammatory pathways, compared to older 12-month-old brains. Importantly, our data revealed that after stroke, most microglia are activated towards a wide spectrum of novel polarization states beyond the standard M1/M2 dichotomy, especially in pathways related to TLR2 and dietary fatty acid signaling. Finally, classes of transcription factors that might potentially regulate microglial activation were identified. These findings should provide a comprehensive database for dissecting microglial mechanisms and pursuing neuroinflammation targets for acute ischemic stroke.

scholarly journals Cortical Spreading Depression Protects against Subsequent Focal Cerebral Ischemia in Rats

1996 ◽  
Vol 16 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Kazushi Matsushima ◽  
Matthew J. Hogan ◽  
Antoine M. Hakim
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Occipital Cortex ◽  
Artery Occlusion ◽  
Microdialysis Probe ◽  
Cerebral Artery Occlusion ◽  
Subcortical Infarct

The possibility that cortical spreading depression (CSD) may have neuroprotective action during subsequent focal cerebral ischemia was examined in rats. Three days before the imposition of focal cerebral ischemia CSDs were elicited by applying potassium chloride (KCl) for 2 h through a microdialysis probe implanted in the occipital cortex. Control animals were handled identically except that saline was infused instead of KCl. Focal ischemia was produced by the intraluminal suture method and cortical and subcortical infarct volumes were measured 7 days later. Neocortical infarct volume was reduced from 124.8 ± 49.5 mm3 in the controls to 62.9 ± 59.5 mm3 in the animals preconditioned with CSD (p = 0.012). There was no difference between the two groups in the subcortical infarct volume or in CBF, measured by the hydrogen clearance method, during or immediately after the ischemic interval. Our data indicate that preconditioning CSD applied 3 days before middle cerebral artery occlusion may increase the brain's resistance to focal ischemic damage and may be used as a model to explore the neuroprotective molecular responses of neuronal and glial cells.

scholarly journals Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ

2016 ◽  
Vol 39 (4) ◽  
pp. 1339-1346 ◽  
Author(s):  
Lichun Pei ◽  
Songyan Meng ◽  
Weigang Yu ◽  
Qiujun Wang ◽  
Fangfang Song ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Protein Level ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Luciferase Assay ◽  
Cerebral Artery Occlusion

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in protecting against distinct brain damages, including ischemia. Our previous data have shown that the protein level of PPARγ is increased in the cortex after middle cerebral artery occlusion (MCAO); PPARγ up-regulation contributes to PPARγ activation and is effective in reducing ischemic damage to brain. However, the regulatory mechanism of PPARγ after focal cerebral ischemia in rats is still unclear. In this study, we evaluated the effect of microRNA on PPARγ in rats subjected to MCAO. Methods: Focal cerebral ischemia was established by surgical middle cerebral artery occlusion; the protein level of PPARγ was detected by Western blotting; the level of microRNA-383 (miR-383) was quantified by real-time PCR; the neurological outcomes were defined by infarct volume and neurological deficits. Luciferase assay was used to identify the luciferase activities of PPARγ and miR-383. Results: We showed here that miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and aggravated neurological damage. Administration of miR-383 antagomir had the opposite effects. Furthermore, we found that PPARγ protein was down-regulated by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat model of MCAO and in primary culture cells. Finally, we found that miR-383 suppressed the luciferase activity of the vector carrying the 3'UTR of PPARγ, whereas mutation of the binding sites relived the repressive effect of miR-383. Conclusion: Our study demonstrated that miR-383 may play a key role in focal cerebral ischemia by regulating PPARγ expression at the post-transcriptional level, and miR-383 may be a potential therapeutic target for stroke.

Induction of ornithine decarboxylase mRNA in transient focal cerebral ischemia in the rat

1997 ◽  
Vol 239 (2-3) ◽  
pp. 69-72 ◽  
Author(s):  
Riitta Keinänen ◽  
Susanna Miettinen ◽  
Juha Yrjänheikki ◽  
Jari Koistinaho
Keyword(s):  
Cerebral Ischemia ◽  
Ornithine Decarboxylase ◽  
Focal Cerebral Ischemia ◽  
Transient Focal Cerebral Ischemia
Sign in / Sign up

Export Citation Format

Share Document