scholarly journals Hyperbaric Oxygen Improves Cerebral Ischemia/Reperfusion Injury in Rats Probably via Inhibition of Autophagy Triggered by the Downregulation of Hypoxia-Inducing Factor-1 Alpha

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Cuiting Wang ◽  
Feng Niu ◽  
Ningna Ren ◽  
Xiaokun Wang ◽  
Hequan Zhong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hyperbaric Oxygen ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Treatment Method ◽  
Male Rats ◽  
Sprague Dawley ◽  
Mortality And Morbidity ◽  
Bonferroni Test

Ischemic stroke, accompanied with high mortality and morbidity, may produce heavy economic burden to societies and families. Therefore, it is of great significance to explore effective therapies. Hyperbaric oxygen (HBO) is a noninvasive, nondrug treatment method that has been proved able to save ischemic penumbra by improving hypoxia, microcirculation, and metabolism and applied in various ischemic diseases. Herewith, we fully evaluated the effect of HBO on ischemic stroke and investigated its potential mechanism in the rat ischemia/reperfusion(I/R) model. Sixty Sprague-Dawley male rats were randomly divided into three groups—sham group, MCAO group, and MCAO+HBO group. In the latter two groups, the middle cerebral artery occlusion was performed (MCAO) for 2 hours, and then the occlusion was removed in order to establish the ischemic/reperfusion model. Subsequently, HBO was performed immediately after I/R (2 hours per day for 3 days). 72 hours after MCAO, the brain was dissected for our experiment. Finally, the data from three groups were analyzed by one-way analysis of variance (ANOVA) and followed by a Bonferroni test. In this article, we reported that HBO effectively reduced the infarction and edema and improved neurological functions to a certain extent. As shown by western blot analysis, HBO significantly reduced autophagy by regulating autophagy-related proteins (mTOR, p-mTOR, Atg13, LC3B II and LC3B II) in the hippocampus 72 hours after I/R, which was accompanied by inhibiting the expression of hypoxia inducible factor-1α (HIF-1α) in hippocampus. The results suggest that HBO may improve cerebral I/R injury, possibly via inhibiting HIF-1α, the upstream molecule of autophagy, and therefore, subsequently inhibiting autophagy in the rat model of ischemic stroke.

scholarly journals Effect of different periods of hyperbaric oxygen on ischemia-reperfusion injury of rat small bowel

2008 ◽  
Vol 23 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Paulo Roberto Bertoletto ◽  
José Carlos Chaves ◽  
Anna Tereza Negrini Fagundes ◽  
Ricardo Santos Simões ◽  
Celina Tizuko Fujiyama Oshima ◽  
...  
Keyword(s):  
Small Bowel ◽  
Reperfusion Injury ◽  
Hyperbaric Oxygen ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Favorable Effect ◽  
Ischemic Insult ◽  
Reperfusion Period ◽  
Intestine Mucosa

PURPOSE: To determine whether hyperbaric oxygen (HBO) could effectively protect the small intestine mucosa against an ischemic insult, according to different periods of application. METHODS: The gut of 32 male rats was subjected to 60-min ischemia (clamping the mesenteric artery and vein); After they were further reperfused upon clamp opening during 60 min. Animal groups were as follows. GII = placed on HBO during the ischemia period; GIII = placed on HBO during reperfusion; GIV = treated with HBO throughout the ischemia-reperfusion period. Some animals (GI) did not receive HBO treatment at all and served as reference of ischemia-reperfusion injury (IR). HBO was carried out in a cylindrical acrylic chamber (2.0 ATA). Samples of small bowel were prepared for H.E staining for histological evaluations. RESULTS: The histological injury of mucosa was significantly less when HBO was administered during the ischemia period (17.6 ± 0.6) as compared with the IR (21.3 ± 1.8). HBO was not effective when applied during reperfusion (23.1 ± 2.1) or during the ischemia plus reperfusion period (18.7 ± 1.9). The thickness of the mucosa was preserved by HBO in ischemia (327.50 ± 30.23 µm) in comparison with the IR (172.79 ± 5.95 µm). In the periods of reperfusion (162.50 ± 6.05 µm) and ischemia plus reperfusion (296.49 ± 20.01 µm) the mucosa revealed a structural injury. CONCLUSION: Hyperbaric oxygen affects the ischemic insult of small bowel, being the favorable effect obtained when hyperbaric oxygen was administered early in the ischemic period.

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 Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shi Shu ◽  
Chun-Ming Li ◽  
Yan-Li You ◽  
Xiao-Lu Qian ◽  
Shuang Zhou ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Neurological Deficit ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Male Rats ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sham Operation Group

Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed.Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats.Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis.Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h.Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

scholarly journals Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury

2021 ◽  
Vol 13 ◽  
Author(s):  
Luoan Shen ◽  
Qinyi Gan ◽  
Youcheng Yang ◽  
Cesar Reis ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Time Window ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Supply And Demand ◽  
Reperfusion Therapy ◽  
Neuroprotective Effects ◽  
Mortality And Morbidity

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction. Mitophagy is a type of selective autophagy referring to the process of specific autophagic elimination of damaged or dysfunctional mitochondria to prevent the generation of excessive reactive oxygen species (ROS) and the subsequent cell death. Recent advances have implicated the protective role of mitophagy in cerebral ischemia is mainly associated with its neuroprotective effects in I/R injury. This review discusses the involvement of mitochondria dynamics and mitophagy in the pathophysiology of ischemic stroke and I/R injury in particular, focusing on the therapeutic potential of mitophagy regulation and the possibility of using mitophagy-related interventions as an adjunctive approach for neuroprotective time window extension after ischemic stroke.

Bardoxolone Ameliorates Cerebral Ischemia/ Reperfusion Injury in Male Rats

2019 ◽  
Vol 22 (04) ◽  
pp. 122-130
Author(s):  
Rihab H Al-Mudhaffer ◽  
Laith M Abbas Al-Huseini ◽  
Saif M Hassan ◽  
Najah R Hadi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

scholarly journals The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

2014 ◽  
Vol 6 (1) ◽  
pp. 46 ◽  
Author(s):  
AhmetA Sancaktutar ◽  
MehmetN Bodakci ◽  
NamıkK Hatipoglu ◽  
Kemal Basarılı ◽  
Haluk Soylemez ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Male Rats ◽  
Protective Effects ◽  
Renal Ischemia Reperfusion Injury

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

2006 ◽  
Vol 291 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
Zhengrong Guan ◽  
Glenda Gobé ◽  
Desley Willgoss ◽  
Zoltán H. Endre
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Endothelial Nitric Oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U) or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 μM furosemide. Autoregulation was enhanced by Nω-nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

Abstract 300: Topical Application of IcyHot Reduces Myocardial Infarct Size in Rodents by a TRPA1-dependent Mechanism

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yun Wu ◽  
Yao Lu ◽  
Eric R Gross
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Sprague Dawley ◽  
Area At Risk ◽  
Reactive Aldehydes

Toxic reactive aldehydes are formed during ischemia-reperfusion. The ion channel transient receptor potential ankryin 1 (TRPA1) is irreversibly modified by reactive aldehydes which can cause calcium influx and cell death. Here we tested whether topically applied creams containing a reversible TRPA1 agonist could reduce myocardial infarct size. Male Sprague-Dawley rats 8-10 weeks age were subjected to an in vivo myocardial ischemia-reperfusion model of 30 minutes of left anterior descending (LAD) coronary artery ischemia followed by 2 hours reperfusion. Prior to ischemia, rats were untreated or had 1g of cream applied to the abdomen. The creams tested were IcyHot, Bengay, Tiger Balm, or preparation H (Fig. 1A). Hearts were negatively stained for the area at risk and the infarct size was determined by using TTC staining (Fig. 1B). A subset of rodents prior to receiving IcyHot also received an intravenous bolus of the TRPA1 antagonist TCS-5861528 (1mg/kg) or AP-18 (1mg/kg). Interestingly, both IcyHot and Bengay reduced myocardial infarct size compared to untreated rodents (Fig. 1C and 1D IcyHot: 41±3%*, Bengay: 50±2%* versus control 62±1%, n=6/group, *P<0.001). Both preparation H and Tiger Balm failed to reduce myocardial infarct size (Tiger Balm: 63±2%, preparation H 59±2%). Giving a TRPA1 antagonist prior to IcyHot also blocked the reduction in infarct size. Our additional data also indicates the methyl salicylate (mint) in IcyHot and Bengay is the agent that limits myocardial infarct size. Since IcyHot and Bengay are safely used by humans, targeting TRPA1 by using products such as these could be quickly translatable and widely used to reduce ischemia-reperfusion injury.

Effects of hyperbaric oxygen pretreatment on brain antioxidant capacity in rats with decompression sickness

2021 ◽  
pp. 287-295
Author(s):  
Ya Li ◽  
◽  
Xiaona Xu ◽  
Junxiang Bao Bao ◽  
Wenlan Wang ◽  
...  
Keyword(s):  
Hyperbaric Oxygen ◽  
Decompression Sickness ◽  
Neuroprotective Effect ◽  
Male Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Rat Models ◽  
Metal Elements ◽  
Flame Atomic Absorption ◽  
Brain Tissues

Objective: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. Methods: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. Results: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. Conclusion: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chandu Vemuri ◽  
Junjie Chen ◽  
Rohun U Palekar ◽  
John S Allen ◽  
Xiaoxia Yang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Warm Ischemia ◽  
P Value ◽  
Sprague Dawley ◽  
Histologic Analysis ◽  
Microvascular Thrombosis

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis. Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining). Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1). Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.

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