scholarly journals Dynamics of Extracellular Metabolites in the Striatum after Middle Cerebral Artery Occlusion in the Rat Monitored by Intracerebral Microdialysis

1989 ◽  
Vol 9 (5) ◽  
pp. 607-616 ◽  
Author(s):  
L. Hillered ◽  
A. Hallström ◽  
S. Segersvärd ◽  
L. Persson ◽  
U. Ungerstedt
Keyword(s):  
Amino Acids ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Intracerebral Microdialysis ◽  
Dopamine Metabolites ◽  
Cerebral Artery Occlusion

The aim of this study was to measure changes in the extracellular fluid (ECF) concentration of lactate, pyruvate, purines, amino acids, dopamine, and dopamine metabolites in the striatum of rats subjected to focal cerebral ischemia, using intracerebral microdialysis as the sampling technique. Microdialysis probes were inserted into the lateral part of the caudate-putamen bilaterally 2 h before the experiment. Ischemia was induced by permanent middle cerebral artery occlusion (MCAO) on the left side. Microdialysis samples were analyzed by high performance liquid chromatography. Following MCAO, the concentration of lactate, adenosine, inosine, and hypoxanthine rose markedly in the ECF on the occluded side, while there was no significant change in pyruvate. These changes were accompanied by dramatically elevated levels of aspartate, glutamate, taurine, γ-aminobutyric acid, and dopamine. There was also a marked increase in alanine/tyrosine, while minor or no changes occurred with other amino acids. Concomitantly, the ECF level of the dopamine metabolites 3,4–dihydroxyphenylacetate and homovanillic acid decreased. There was no significant increase in any of the metabolites measured on the right, nonoccluded side. In relation to the concept of excitotoxicity in brain ischemia, it is concluded that during the acute stage of focal cerebral ischemia, the ECF is flooded with both potentially harmful (e.g., aspartate, glutamate, and DA) and protective (e.g., taurine, GABA, and adenosine) agents. The relative importance of these events for the development of cell death in the ischemic penumbra needs to be elucidated. In addition, lactate, inosine, and hypoxanthine, measured in the ECF by intracerebral microdialysis, may prove to have diagnostic and/or prognostic value in neurometabolic monitoring of the ischemic brain.

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.

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