Revascularização do vaso culpado antes da angiografia completa como estratégia para minimizar atrasos na intervenção coronariana percutânea primária em pacientes com IAMCSST: uma meta-análise / Culprit vessel revascularization before complete angiography as a strategy to minimize delays in primary percutaneous coronary intervention in patients with STEMI: a meta-analysis

INTRODUÇÃO: A rápida restauração do fluxo sanguíneo em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) através da intervenção coronariana percutânea (ICP) é crucial para a sobrevivência desta população. As tentativas de diminuir o tempo desde o diagnóstico do IAMCSST até a chegada ao laboratório de cateterismo têm sido extensivamente investigadas. Contudo, faltam estratégias que visem reduzir o tempo intraprocedimento. OBJETIVO: Portanto, realizamos uma meta-análise para avaliar a revascularização do vaso culpado antes da angiografia completa como estratégia para minimizar atrasos na ICP primária em pacientes com IAMCSST. MÉTODOS: Pesquisamos na PubMed, Embase e Cochrane Central. Os desfechos de interesse foram: tempo acesso vascular-balão, tempo porta-balão, tempo primeiro contato médico-balão, mortalidade hospitalar, mortalidade em 30 dias, mortalidade em 1 ano, mortalidade cardíaca em 30 dias, reinfarto em 30 dias, sangramento BARC ≥ tipo 3, encaminhamento para cirurgia de revascularização do miocárdio e FEVE %. A análise estatística foi realizada no programa R (versão 4.3.2). A heterogeneidade foi avaliada com estatística I2. RESULTADOS: Incluímos 2.050 pacientes de 6 estudos, dos quais 2 eram ECRs e 4 estudos observacionais. A mediana de acompanhamento variou de 17 a 65 meses. A revascularização do vaso culpado antes da angiografia completa foi associada a uma diminuição estatisticamente significativa dos tempos: acesso vascular-balão (MD -6,79; IC 95% [- 8,00, - 5,58]; p<0,01; I2 = 82%) e porta-balão (MD -9,02; IC 95% [− 12,83, − 5,22]; p<0,01; I2 =93%). Além disso, a abordagem inicial da artéria culpada com a ICP foi associada ao aumento da FEVE (MD 1,90; IC95% 0,77 − 3,04]; p<0,01; I2 =82%). Não houve diferença significativa entre os grupos em termos de mortalidade hospitalar (RR 1,15; IC 95% 0,34 - 3,87; p=0,823; I2 =0%), mortalidade em 1 ano (RR 0,83; IC 95% 0,59 - 1,17; p =0,282; I2 =0%), mortalidade cardíaca em 30 dias (RR 0,77; IC 95% 0,38 - 1,57; p=0,472; I2 =0%) e reinfarto em 30 dias (RR 1,02; IC 95% 0,29 - 3,58; p=0,980; CONCLUSÃO: Nesta meta-análise abrangente de pacientes que apresentaram IAMCSST, a realização da ICP na lesão culpada antes da angiografia coronária completa levou a tempos de reperfusão significativamente mais curtos, sem diferenças discerníveis nas taxas de complicações.

Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

Impaired Ischemia-Reperfusion Responses in the Hearts of Aged Male and Female Offspring of Obese Rats.

Maternal obesity predisposes offspring (F1) to cardiovascular disease. To evaluate basal heart function and ischemia-reperfusion (IR) responses in F1 males and females of obese mothers, female Wistar rats (F0) were fed chow or an obesogenic (MO) diet from weaning through pregnancy and lactation. Non-sibling F1 males and females were weaned to chow at postnatal day (PND) 21 and euthanized at PND 550. Offspring of MO mothers (MOF1) rarely survive beyond PND 650. Hearts were immediately isolated from euthanized F1s and subjected to 30 min ischemia with 20 min reperfusion. Retroperitoneal fat, serum triglycerides, glucose, insulin, and insulin resistance were measured. Baseline left ventricular developed pressure (LVDP) was lower in male and female MOF1 than in controls. After global ischemia, LVDP in control (C) male and female F1 recovered 78 and 83%, respectively, while recovery in MO male and female F1 was significantly lower at 28 and 52%, respectively. Following the IR challenge, MO hearts showed a higher functional susceptibility to reperfusion injury, resulting in lower cardiac reserve than controls in both sexes. Female hearts were more resistant to IR. Retroperitoneal fat was increased in male MOF1 vs. CF1. Circulating triglycerides and insulin resistance were increased in male and female MOF1 vs. CF1. These data show that MO programming reduces F1 cardiac reserve associated with age-related insulin resistance in a sex-specific manner.

A Brain Ischemia-Reperfusion Model for the Study of Tau Phosphorylation and O-GlcNAcylation.

Cerebral ischemia produces a decrease, loss, or instability of the assembly processes in the neuronal cytoskeleton, related to the alteration in the normal processes of phosphorylation of the Tau protein, triggering its hyperphosphorylation and altering the normal processes of formation of neuronal microtubules. Here we describe the methods used to study the impact of middle cerebral artery occlusion (MCAo) on neurological functions and Tau phosphorylation in Wistar rat brain.

E-cadherin and NF-κB expression in the vagina after ovarian ischemia and reperfusion

Purpose: To investigate inflammation and cell adhesion molecules in the vagina after ovarian ischemia-reperfusion (IR) injury. Methods: 20 Wistar albino female rats were divided into two groups: control, and IR groups. In IR group, blood flow was restricted for 2 hours for ovarian ischemia. Then, tissues were re-blood 2 hours for reperfusion. Vagina tissues were excised and processed for histopathological analysis. Histopathological and biochemical follow-ups were performed. Results: Both malondialdehyde and myeloperoxidase values were increased in IR group compared to control group. Glutathione content was decreased in IR group compared to control group. Epithelial degeneration, inflammation, dilatation, and nuclear factor-κB (NF-κB) expression were increased in IR group compared to control group. E-cadherin expression was significantly decreased in IR group. In the IR group, E-cadherin showed a positive reaction in adenomas, gland-like cryptic structures, cellular junctions with clustered inflammatory cells. In the IR group, NF-κB expression was increased in basement membrane, inflammatory cells, in blood vessels. Conclusions: Ovarian ischemia caused degeneration of epithelial cells in the vaginal region and disruptions in the cell junction complex, which leads to activation of E-cadherin and NF-κB signaling pathway and alterations in reproductive and embryonal development in the vaginal region.

Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats

Purpose: This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. Methods: Fifty male Sprague Dawley rats (250­300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid­Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. Results: Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. Conclusions: Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.

Fasudil mediates neuroprotection in ischemia/reperfusion by modulating the ROCK-PPARα-NOX axis.

PURPOSE: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. METHODS: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023. Mice were treated with Fasudil and saline; 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to analyze cerebral infarction. PPARα and Rho-associated protein kinase (ROCK) expression were detected using Western blot, and the expression of NADPH subunit Nox2 mRNA was detected using real-time polymerase chain reaction. The NADPH oxidase activity level and reactive oxygen species (ROS) content were also investigated. RESULTS: After cerebral ischemia, the volume of cerebral necrosis was reduced in wild-type mice treated with Fasudil. The expression of PPARα was increased, while ROCK was decreased. Nox2 mRNA expression, NADPH oxidase activity, and ROS content decreased. There were no significant changes in cerebral necrosis volumes, NADPH oxidase activity, and ROS content in the PPARα KO mice treated with Fasudil. CONCLUSIONS: In mice, the neuroprotective effect of Fasudil depends on the expression of PPARα induced by ROCK-PPARα-NOX axis-mediated reduction in ROS and associated oxidative damage.

Morbimortality and determinants of reperfusion in ischemic stroke.

BACKGROUND: Cerebrovascular accident (or stroke) and ischemic heart disease are the the major causes of death in the world. It is estimated that about 85% of strokes are ischemic in origin. Reperfusion therapy in the acute phase of ischemic stroke with a recombinant human tissue plasminogen activator is effective, but some factors influence the success of this treatment. OBJECTIVE: The aim of this study was to evaluate clinical aspects and possible determinants for reperfusion after venous thrombolysis. METHODS: This is a retrospective, cross-sectional, observational study based on a review of hospital records of inpatients diagnosed with ischemic stroke treated with intravenous thrombolysis, the main outcome being reperfusion or not. RESULTS: Data from this study revealed a predominance of females in the group of reperfused patients and males in the non-reperfused group, both maintaining moderate severity on the National Institutes of Health Stroke Scale and admission without statistical significance (p>0.18). In addition, the mean admission severity score was 13.2 for the group of reperfused patients and 14.2 for those not reperfused, and the mean ejection fraction of both groups was within normal functionality, with a mean of 0.50 for reperfused patients and 0.62 for non-reperfused patients. CONCLUSION: We found an association between successful venous chemical thrombolysis reperfusion and lower mortality in patients with acute stroke.

Reperfusion therapy for acute ischemic stroke: where are we in 2023?

Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Effects of daidzein on rat ovary against ischemia-reperfusion.

PURPOSE: Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques. METHODS: Thirty Sprague Dawley female rats were categorized into three groups as sham, I/R group, and I/R+daidzein groups. Bloods were analyzed for malondialdehyde (MDA), glutathione peroxidase (GSH), and myeloperoxidase (MPO), and ovaries were processed for histological tissue protocol. RESULTS: Both MDA and MPO values were increased in I/R group compared to sham and I/R+daidzein groups. GSH content was increased in I/R+daidzein group compared to I/R groups. In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. In I/R+daidzein group, daidzein improved pathologies. In the I/R group, Bax expression was positive with follicular cells, granulosa cells and inflammatory cells. In the I/R+daidzein group, positive Bax reaction was observed in the epithelial, antral, and inflammatory cells. In I/R group, Bcl-2 reaction was in germinative epithelial cells, cells of antral follicle. In the I/R+daidzein group, Bcl-2 expression level was reduced after daidzein treatment. CONCLUSIONS: After the I/R procedure, ovarian cells and follicles were degenerated with apoptosis and inflammation. After daidzein treatment, Bax and Bcl-2 signal were decreased. It was observed that daidzein stopped the apoptotic process.

Effects of erythropoietin on ischaemia-reperfusion when administered before and after ovarian tissue transplantation in mice.

RESEARCH QUESTION: Is the optimal timing for administering erythropoietin to minimize ischaemic injury in ovarian tissue transplantation before ovary removal for cryopreservation and subsequent transplantation or after transplantation? DESIGN: Thirty Swiss mice (nu/nu) were divided into three groups: treatment control group (n = 10); erythropoietin before harvesting group (EPO-BH) (n = 10) and erythropoietin after transplantation group (EPO-AT) (n = 10). Animals underwent bilateral ovariohysterectomy and their hemiovaries were cryopreserved by slow freezing. At the same time, previously cryopreserved hemiovaries were transplanted subcutaneously in the dorsal region. Erythropoietin (250 IU/kg) and sterile 0.9% saline solution were administered every 12/12 h over 5 consecutive days in the EPO-AT and EPO-BH groups, respectively. RESULTS: Administration of erythropoietin in the EPO-AT group improved the viability of ovarian follicles, reducing degeneration and increasing the number of morphologically normal growing follicles at 14 days after transplantation compared with the EPO-BH group (P = 0.002). This group also showed higher percentages of proliferative follicles at 7 days after transplantation (P ≤ 0.03), increased blood vessel count (P ≤ 0.03) and greater tissue area occupied by blood vessels at days 7 and 14 after transplantation (P ≤ 0.03), compared with hormone administration before cryopreservation (EPO-BH group) and the treatment control group. Additionally, treatment with erythropoietin before or after transplantation reduced fibrotic areas at 7 days after transplantation (P = 0.004). CONCLUSION: Erythropoietin treatment after transplantation reduced ischaemic damage in transplanted ovarian tissue, increased angiogenesis, maintenance of ovarian follicle proliferation and reduced fibrosis areas in the grafted tissue.

Could retrograde reperfusion combined with washout technique broaden the applicability of marginal grafts in liver transplantation? Intra-operative and short-term outcomes of a prospective cohort.

INTRODUCTION: many revascularization techniques were designed to reduce the imbalance of ischemia-reperfusion injury. This study's objective is to evaluate retrograde reperfusion (RR) compared to sequential anterograde reperfusion (AR), with and without the washout technique (WO). METHOD: this prospective cohort study collected data from 94 deceased donor orthotopic liver transplants and divided it into three groups: RR with WO (RR+WO), AP with WO (AR+WO), and AP without WO (AR). This study did not assign the reperfusion technique to the participants. The primary outcome considered the early graft dysfunction, and secondary outcomes included post-reperfusion syndrome (PRS), post-reperfusion lactate, surgery fluid balance, and vasoactive drug dose during the surgery. RESULTS: 87 patients were submitted to the final analysis-29 in the RR+WO group, 27 in the AR+WO group, and 31 in the AR group. Marginal grafts prevalence was not significantly different between the groups (34% vs. 22% vs. 23%; p=0.49) and early graft dysfunction occurred at the same rate (24% vs. 26% vs. 19%; p=0.72). RR+WO reduced serum post-reperfusion lactate (p=0.034) and the incidence of significant PRS (17% vs. 33% vs. 55%; p=0.051), but norepinephrine dosing >0.5mcg/kg/min were not different during the surgery (20,7% vs. 29,6% vs. 35,5%, p=0.45). CONCLUSIONS: primary outcome was not significantly different between the groups; however, intraoperative hemodynamic management was safer using the RR+WO technique. We theorized that the RR+WO technique could reduce the incidence of PRS and benefit marginal graft survival following diseased donor orthotopic liver transplantation.

Tocilizumab is effective in preventing ovarian injury induced by ischemia- reperfusion in rats.

Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1ß, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.

Severe muscle damage after a short period of ischemia and reperfusion in an animal model.

BACKGROUND: Skeletal muscle ischemia-reperfusion injuries result in a loss of contractile function, leading to limb disability or amputation. Ischemia causes hypoxia and cellular energy failure, which is aggravated by reperfusion due to the inflammatory response and oxidative stress. The consequences of the injury vary according to the duration of the period of ischemia and reperfusion. Therefore, the present work aims to evaluate ischemia-reperfusion injuries induced in the skeletal muscles of Wistar rats submitted to 3 different application periods based on morphological and biochemical parameters. METHODS: For this, a tourniquet was applied to the root of the animals' hind limbs, occluding arterial and venous blood flow, and it was followed by reperfusion-the removal of the tourniquet. The groups were: control (without tourniquet); I30'/R60' (30 minutes of ischemia and 1 hour of reperfusion); I120'/R120' (2 hours and 2 hours); and I180'/R180' (3 hours and 3 hours). RESULTS: All ischemia-reperfusion groups showed characteristics of muscle injury. Microscopic analyses of the extensor digitorum longus, soleus, tibialis anterior, and gastrocnemius muscles showed a significant increase in the number of injured muscle fibers in the ischemia-reperfusion groups compared to the control group. There were also significant differences between the ischemia-reperfusion groups in all muscles, showing a progressive increase in the degree of injury. The quantification of the number of injured muscle fibers between the muscles revealed that at I30'/R60', the soleus muscles had a higher number of injuries in relation to the other muscles, with statistical significance. In the I120'/R120' group, the gastrocnemius muscles presented a significantly greater number of injured fibers. There were no significant differences in the I180'/R180' group. The serum levels of creatine kinase in the I180'/R180' group were significantly higher than in the control and I30'/R60' groups. CONCLUSIONS: Therefore, it was evident that the 3 ischemia-reperfusion models used were capable of causing cell damage, with these findings being more pronounced in the I180'/R180' group.

The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: Biochemical and histopathological assessment.

The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.

Ovarian hormones influence immune response to liver ischemia-reperfusion.

Liver injury occurs after ischemia and reperfusion (IR), as seen in transplant settings. Sex hormones have been implicated in many pathophysiological mechanisms in females and this could lead to liver protection under inflammatory reperfusion conditions where an excessive immune response occurs. Despite such assumptions, this fact needs to be further investigated. To address this, female and male C57BL/6J mice (8-12 weeks old) were studied. Bilateral ovariectomy (OVX) was performed in females to decrease estradiol levels. IR was performed, and after two weeks, all animals underwent a sham control operation or IR with euthanasia at the following time points after reperfusion: 6, 12, 24, and 48 h. IR triggered an inflammatory process in the liver with recruitment of neutrophils into the parenchyma of male mice. The female sham mice were protected against liver IR presenting no alteration of aminotransferase (ALT) levels compared to males. OVX caused loss of protection, increasing hepatic injury as represented by increased ALT levels and myeloperoxidase (MPO) activity. Female sham mice showed increased Akt phosphorylation and activation, while males showed reduced Akt activation. Estradiol pretreatment recovered ALT levels after IR injury, which was associated with decreased liver injury.

Global cerebral ischemia followed by long-term reperfusion promotes neurodegeneration, oxidative stress, and inflammation in the small intestine in Wistar rats.

AIMS: Brain ischemia and reperfusion may occur in several clinical conditions that have high rates of mortality and disability, compromising an individual's quality of life. Brain injury can affect organs beyond the brain, such as the gastrointestinal tract. The present study investigated the effects of cerebral ischemia on the ileum and jejunum during a chronic reperfusion period by examining oxidative stress, inflammatory parameters, and the myenteric plexus in Wistar rats. MAIN METHODS: Ischemia was induced by the four-vessel occlusion model for 15 min with 52 days of reperfusion. Oxidative stress and inflammatory markers were evaluated using biochemical techniques. Gastrointestinal transit time was evaluated, and immunofluorescence techniques were used to examine morpho-quantitative aspects of myenteric neurons. KEY FINDINGS: Brain ischemia and reperfusion promoted inflammation, characterized by increases in myeloperoxidase and N-acetylglycosaminidase activity, oxidative stress, and lipid hydroperoxides, decreases in superoxide dismutase and catalase activity, a decrease in levels of reduced glutathione, neurodegeneration in the gut, and slow gastrointestinal transit. SIGNIFICANCE: Chronic ischemia and reperfusion promoted a slow gastrointestinal transit time, oxidative stress, and inflammation and neurodegeneration in the small intestine in rats. These findings indicate that the use of antioxidant and antiinflammatory molecules even after a long period of reperfusion may be useful to alleviate the consequences of this pathology.

Caryocar brasiliense peel ethanolic extract has neuroprotective potential and reduces the activation of ERK1/2 in the ischemia and reperfusion brain acute phase in the rat.

Oxidative stress induced by ischemia and reperfusion (I/R) injury results in cell death by necrosis or apoptosis and triggers the activation of different intracellular pathways, such as mitogen-activated protein activated kinases. Pequi (Caryocar brasiliense) peel, residue of a fruit from Brazilian savannah-like vegetation, has phenolic compounds that have been demonstrated to have antioxidant effects in vitro. The present study aimed to evaluate the neuroprotective effects of C. brasiliense peel ethanolic extract (CBPE) against transient global I/R injury in the rat brain. Global ischemia for 5, 20, and 45 min followed by 2 h of reperfusion caused a significant time-dependent increase in the number of ischemic neurons (p ≤ 0.05); increased immunoreactivity of cleaved caspase-3 (CASP3); and activated extracellular signal-regulated kinase (ERK) 1/2. Pretreatment with CBPE (600 mg/kg, oral) or vitamin E (0.6 mg, oral) for 30 days showed significant protection against acute brain injury induced by 20 and 45 min or 5 min of ischemia, respectively, by reducing the cortical ischemic neuron count (p ≤ 0.05) and p-ERK1/2 immunoreactivity. In addition, active c-Jun N-terminal kinase (JNK) immunoreactivity was reduced in animals not subjected to ischemia. Therefore, we suggest an association between vitamin E and CBPE, which may generate a better neuroprotective response. Interestingly, mainly in the hippocampus and oligodendrocytes, high dose CBPE increase the number of isquemic neurons and of CASP3 immunoreactive cells in animals subjected or not to ischemia, which was not verified in the vitamin E group. Therefore, additional studies are recommended to verify the safety of the continuous use of CBPE.

Ischemic preconditioning and exercise performance: are the psychophysiological responses underestimated?

The findings of the ischemic preconditioning (IPC) on exercise performance are mixed regarding types of exercise, protocols and participants' training status. Additionally, studies comparing IPC with sham (i.e., low-pressure cuff) and/or control (i.e., no cuff) interventions are contentious. While studies comparing IPC versus a control group generally show an IPC significant effect on performance, sham interventions show the same performance improvement. Thus, the controversy over IPC ergogenic effect may be due to limited discussion on the psychophysiological mechanisms underlying cuff maneuvers. Psychophysiology is the study of the interrelationships between mind, body and behavior, and mental processes are the result of the architecture of the nervous system and voluntary exercise is a behavior controlled by the central command modulated by sensory inputs. Therefore, this narrative review aims to associate potential IPC-induced positive effects on performance with sensorimotor pathways (e.g., sham influencing bidirectional body-brain integration), hemodynamic and metabolic changes (i.e., blood flow occlusion reperfusion cycles). Overall, IPC and sham-induced mechanisms on exercise performance may be due to a bidirectional body-brain integration of muscle sensory feedback to the central command resulting in delayed time to exhaustion, alterations on perceptions and behavior. Additionally, hemodynamic responses and higher muscle oxygen extraction may justify the benefits of IPC on muscle contractile function.