scholarly journals Effects of Normobaric Hyperoxia in a Rat Model of Transient Focal Cerebral Ischemia and Reperfusion

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 316-316
Author(s):  
Aneesh B Singhal ◽  
Xiaoying Wang ◽  
Eng H Lo
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Blue Dye ◽  
Ischemia And Reperfusion ◽  
Normobaric Hyperoxia ◽  
Doppler Flowmetry ◽  
Normobaric Oxygen ◽  
Cerebral Ischemia And Reperfusion

3 Background: The role of therapeutic oxygen in treatment of acute stroke is controversial. Oxygen improves cellular aerobic metabolism and can salvage ischemic tissue. However, oxygen free radicals can increase blood brain barrier (BBB) damage, and oxygen can induce vasoconstriction, which could worsen stroke outcome. We studied the effects of normobaric oxygen in cerebral ischemia and reperfusion. Methods: Rats were subjected to normobaric hyperoxia (FiO2 100%) or normoxia (FiO2 30%) during two hour filament occlusion and one hour reperfusion of the middle cerebral artery. Twenty-four hour infarct volumes, regional cerebral blood flow (rCBF) using laser Doppler flowmetry, and severity of BBB damage (assessed by quantifying Evan’s Blue dye (EB) leakage after one hour of reperfusion) were compared between groups. Results: Physiological parameters were similar in hyperoxic and control groups, except for paO2, which was expectedly higher in the hyperoxic group (pO2 484 mm Hg) as compared to controls (pO2 118 mm Hg). Mean rCBF dropped to 25% after onset of ischemia and recovered to 75–90% after arterial unocclusion, indicating successful reperfusion. Mean total (right hemispheric) infarct volume was 65 mm 3 in the hyperoxia group and 209 mm 3 in controls, p<0.001. The reduction in infarct volume was mostly in the cortex, where mean infarct volume was 11 mm 3 in hyperoxic rats and 129 mm 3 in controls (p<0.001). Mean striatal infarct volume was 54 mm 3 in hyperoxic rats and 80 mm 3 in controls (p<0.06). Mean total EB leak was 1592 ng/g in hyperoxic and 3955 ng/g in control rats (p<0.02), suggesting reduced BBB damage in hyperoxia. However, BBB damage and EB leak are likely related to infarct volume; after normalising for infarct volume, mean EB leak was 17 ng/mm3 in the hyperoxia group and 14 ng/mm3 in controls (p=0.5). Conclusion: Total and cortical infarct volumes can be significantly reduced with normobaric hyperoxia during transient cerebral ischemia and reperfusion. Hyperoxia does not decrease blood flow to ischemic brain, and its benefit in reducing infarct volume may outweigh any potential damage from BBB damage.

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 Acute Improvement in Histological Outcome by MK-801 following Focal Cerebral Ischemia and Reperfusion in the Cat Independent of Blood Flow Changes

1992 ◽  
Vol 12 (3) ◽  
pp. 390-399 ◽  
Author(s):  
Laszlo Dezsi ◽  
Joel H. Greenberg ◽  
Janos Hamar ◽  
John Sladky ◽  
Andrea Karp ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Left Middle Cerebral Artery ◽  
Ischemia And Reperfusion ◽  
Partial Recovery ◽  
Mk 801 ◽  
Cerebral Ischemia And Reperfusion ◽  
Flow Changes

The present study reports on the acute effects of MK-801 on the histopathological outcome and blood flow changes during focal cerebral ischemia and reperfusion. In addition, acute changes in the EEG and blood pressure are also reported. In 16 halothane-anesthetized cats, the left middle cerebral artery (MCA) was occluded for 2 h followed by 4 h of reperfusion. Thirty minutes after the onset of ischemia, eight animals were treated with 1 mg/kg of MK-801, while eight animals received saline. Blood flow from the peripheral MCA territory was measured with H2 clearance. There was a comparable reduction in blood flow (down to 20% of control) in the ischemic gyri of the two groups followed by a partial recovery after recirculation. There was a similar decrease in the EEG amplitude over the ischemic central MCA territory in the treated and the untreated group. Treatment with MK-801 induced a burst suppression in the EEG and a transient drop (11.4 ± 6.5 mm Hg) in the mean arterial pressure. The volume of early ischemic damage decreased by one-third in the MK-801-treated group compared to the untreated one, both in the total hemisphere (from 29 ± 10 to 20 ± 5%) and in the hemispheric cortex (range 36 ± 8 to 24 ± 13%). A major fraction of this improvement was localized to the middle and posterior parietal (mainly perifocal) regions of the MCA territory. These results show that in our model, MK-801 improves histopathological outcome despite the lack of apparent effect on the cortical blood flow, and an adverse effect on the systemic blood pressure. This is the first report that describes data on a reproducible model of reperfusion after temporary occlusion of the MCA in a cat, extending the findings of the Glasgow group, who observed similar neuroprotection in models of permanent MCA occlusion.

scholarly journals E-Selectin in Focal Cerebral Ischemia and Reperfusion in the Rat

1996 ◽  
Vol 16 (6) ◽  
pp. 1126-1136 ◽  
Author(s):  
Rui Lan Zhang ◽  
Michael Chopp ◽  
Zheng G. Zhang ◽  
M. Laurie Phillips ◽  
Craig L. Rosenbloom ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Cell Damage ◽  
Leukocyte Adhesion ◽  
Infarct Volume ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Ischemic Lesion ◽  
Mca Occlusion ◽  
Cerebral Ischemia And Reperfusion

The selectin family of glycoproteins facilitates the early phase of polymorphonuclear leukocyte adhesion to the endothelial cell and, thus, may promote ischemic cell damage. To evaluate E-selectin in the pathogenesis of focal cerebral ischemia and reperfusion injury, we cloned rat E-selectin cDNA and measured the temporal profiles E-selectin mRNA (Northern blot) and protein (immunohistochemistry) during (1 h of ischemia) and after (up to 1 week) transient (2 h) middle cerebral artery (MCA) occlusion in the male Wistar rat. We also tested the effect on these rats of administration of CY-1503, an analog of sialyl Lewisx (SLex), on ischemia cell damage. mRNA for E-selectin was first detected in the ischemic hemisphere at 2 h of reperfusion and persisted to 46 h of reperfusion. E-selectin (protein) was localized to microvessels within the ischemic lesion at 0 h of reperfusion and persisted to 70 h of reperfusion. Treatment of the ischemic animals with CY-1503 (50 mg/kg) (n = 8) significantly reduced infarct volume by 42% ( p < 0.05) and significantly reduced myeloperoxidase immunoreactive cells in the ischemic lesion by 60% ( p < 0.05). These findings provide the first direct evidence for the involvement of E-selectin in transient MCA occlusion in rats and suggest that the E-selectin may facilitate neutrophil adhesion and subsequent cerebral ischemic cell damage.

Abstract WMP37: MicroRNA-29a Protects Against Cerebral Ischemia and Reperfusion Injury by Targeting NADPH Oxidase 4

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yong-Hua Tuo ◽  
Zhong Liu ◽  
Lei Feng ◽  
Zhong-Song Shi
Keyword(s):  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Reperfusion Injury ◽  
Blood Brain Barrier ◽  
Neurological Outcome ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Cerebral Ischemia And Reperfusion

Background: MicroRNA-29a (miR-29a) is involved in regulating cerebral ischemia process, but its underlying mechanism is unclear. We previously showed that inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4) pathway improves the neurological outcome and increases the expression of miR-29a in transient middle cerebral artery occlusion (tMCAO) animal model. This study investigated the role of miR-29a in cerebral ischemia and reperfusion injury after mechanical reperfusion. Methods: The intraluminal filament tMCAO model was established in male rats with 2 hour ischemia followed by reperfusion. The expression of miR-29a and NOX4 in the infarction core and peri-infarct cortex were quantified at 0, 3, 12, and 24 hour after reperfusion. Permanent MCAO model was also evaluated after 2 hour and 24 hour ischemia. Intravenous miR-29a agomir was delivered immediately after reperfusion. Infarct volume, brain water content, neurological score, blood-brain barrier damage, and levels of miR-29a and NOX4 were determined at 24-hour after cerebral ischemia. Results: MiR-29a levels in the infarction core and peri-infarct cortex were significantly decreased at 3 hours after reperfusion in tMCAO group compared with the sham-operated group. The decreased levels of miR-29a lasted for 24 hours after cerebral ischemia. Dual-luciferase reporter system showed that NOX4 was the direct target gene of miR-29a. Intravenous miR-29a agomir increased the expression of miR-29a and suppressed NOX4 up-regulation in both the infarction core and peri-infarct cortex at 24-hour after ischemia compared with the tMCAO group (all p<0.05). Intravenous miR-29a agomir reduced infarct volume (24.7% ± 4.0% versus 37.8% ± 7.5%, p<0.01) at 24-hour after ischemia compared to the tMCAO group. MiR-29a agomir attenuated brain edema and reduced reperfusion-induced blood-brain barrier breakdown, resulting in improved neurological outcome (all p<0.05). Conclusions: MiR-29a overexpression protects against cerebral ischemia and reperfusion injury via downregulating NOX4. Infusion of miR-29a agomir immediately after reperfusion represents a novel adjunctive therapeutic strategy to improve outcome after mechanical reperfusion for acute ischemic stroke.

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