Indomethacin-mediated improvement following middle cerebral artery occlusion in cats

1985 ◽  
Vol 62 (6) ◽  
pp. 874-881 ◽  
Author(s):  
Robert J. Dempsey ◽  
Mark W. Roy ◽  
Kathleen L. Meyer ◽  
David L. Donaldson
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Opposite Hemisphere ◽  
Content Type ◽  
Beneficial Effects ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p < 0.05). This was noted in densely ischemic areas (indomethacin = 84.3%, control = 87.5%), in “penumbra” regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p < 0.05), as was cerebral perfusion (p < 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p < 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p < 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbitalstabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.

Posttraumatic bilateral middle cerebral artery occlusion

1975 ◽  
Vol 42 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Skip Jacques ◽  
C. Hunter Shelden ◽  
D. Thomas Rogers ◽  
Anthony C. Trippi
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Content Type ◽  
Pathophysiological Mechanisms ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ The authors report a case of bilateral posttraumatic middle cerebral artery occlusion. Previously reported unilateral cases are reviewed and possible pathophysiological mechanisms disscussed.

Pathophysiology and treatment of focal cerebral ischemia

1992 ◽  
Vol 77 (3) ◽  
pp. 337-354 ◽  
Author(s):  
Bo K. Siesjö
Keyword(s):  
Free Radicals ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Ischemic Lesion ◽  
Glutamate Antagonists ◽  
Content Type ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues can be salvaged only by recirculation, and any brain damage incurred is delayed, suggesting that the calcium transient gives rise to sustained changes in membrane function and metabolism. If the ischemia is less dense, as in the penumbral zone of a focal ischemic lesion, pump failure may be moderate and the leak may be only slightly or intermittently enhanced. These differences in the pump/leak relationship for calcium explain why calcium and glutamate antagonists may lack effect on the cardiac arrest type of ischemia, while decreasing infarct size in focal ischemia. The adverse effects of acidosis may be exerted by several mechanisms. When the ischemia is sustained, acidosis may promote edema formation by inducing Na+ and Cl− accumulation via coupled Na+/H+ and Cl−/HCO3− exchange; however, it may also prevent recovery of mitochondrial metabolism and resumption of H+ extrusion. If the ischemia is transient, pronounced intraischemic acidosis triggers delayed damage characterized by gross edema and seizures. Possibly, this is a result of free-radical formation. If the ischemia is moderate, as in the penumbral zone of a focal ischemic lesion, the effect of acidosis is controversial. In fact, enhanced glucolysis may then be beneficial. Although free radicals have long been assumed to be mediators of ischemic cell death, it is only recently that more substantial evidence of their participation has been produced. It now seems likely that one major target of free radicals is the microvasculature, and that free radicals and other mediators of inflammatory reactions (such as platelet-activating factor) aggravate the ischemic lesion by causing microvascular dysfunction and blood-brain barrier disruption. Solid experimental evidence exists that the infarct resulting from middle cerebral artery occlusion can be reduced by glutamate antagonists, by several calcium antagonists, and by some drugs acting on Ca++ and Na+ influx. In addition, published reports hint that qualitatively similar results are obtained with drugs whose sole or main effect is to scavenge free radicals. Thus, there is substantial experimental evidence that the ischemic lesions due to middle cerebral artery occlusion can be ameliorated by drugs, sometimes dramatically; however, the therapeutic window seems small, maximally 3 to 6 hours. This suggests that if these therapeutic principles are to be successfully applied to the clinical situation, patient management must change.

Treatment of intraoperative middle cerebral artery occlusion with pentobarbital and extracranial-intracranial bypass

1979 ◽  
Vol 51 (5) ◽  
pp. 710-712 ◽  
Author(s):  
Pablo M. Lawner ◽  
Frederick A. Simeone
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Neurological Deficit ◽  
Artery Occlusion ◽  
Content Type ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ A patient with a meningioma of the medial sphenoid wing underwent inadvertent intraoperative occlusion of the middle cerebral artery. Neurological deficit and infarction were presumably prevented by immediate administration of pentobarbital followed by extracranial-intracranial bypass.

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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