ischemia

Serum/glucose deprivation in cultured PC12 cells is considered an appropriate model for investigating detailed mechanisms of ischemia-induced brain injury. Here, we aimed to study the anti-apoptotic effects of licorice (Glycyrrhiza glabra L.) root extract and carbenoxolone on PC12 cells cultured in the serum/glucose deprivation (SGD) condition.

Cells were incubated with the different concentrations of the G. glabra methanol extract (5-320 µg/ml) and carbenoxolone (0.5-32 µM) for 2 hr before being deprived of serum/glucose. Protection against cytotoxicity, increase in reactive oxygen species (ROS), and apoptosis was analyzed with resazurin, dichlorofluorescein diacetate (DCFH-DA), and western blot, respectively.

Serum/glucose deprivation induced cell death and apoptosis in PC12 cells. Pretreatment with the G. glabra methanol extract at 5-20 µg/ml and carbenoxolone at 0.5-2 µM for 2 hr significantly decreased the cytotoxicity (p<0.05), and pretreatment with the G. glabra methanol extract (5-160 µg/ml) and carbenoxolone (0.5 μM) significantly decreased the ROS content. Pretreatment with the G. glabra methanol extract and carbenoxolone at 5-20 µg/ml significantly prevented from the Poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage.

Taken together, this study confirms the protective and free radical-scavenging potency of licorice extract and carbenoxolone in in vitro model of ischemia. Overall, it seems that pretreatment with the licorice extract and carbenoxolone may potentially slow the progression of brain ischemia.

Eggs, while nutrient-rich, have high cholesterol content. The link between egg consumption and cardiovascular disease (CVD) remains debated. This study investigates how egg intake correlates with minor and major electrocardiogram (ECG) abnormalities, which serve as potential indicators of CVD. In this cross-sectional study, a total of 5,928 participants without cardiovascular disease (CVD), aged between 35 and 65 years, were included. Dietary egg consumption was evaluated using a validated food frequency questionnaire. The Minnesota coding system was employed to identify minor and major ischemic abnormalities on ECG. Odds ratios (ORs) for major and minor ischemic patterns across different egg consumption categories were calculated using multivariable logistic regression. Using several statistical models, this study showed that higher egg consumption was associated with lower odds of isolated major ECG abnormalities in men, but not in women. In the fully adjusted model, consuming more than four eggs per week, compared to the lowest category (<1/week), was correlated with a 40% decrease in the odds of major ischemic changes on ECG in men (OR: 0.60, 95% CI: 0.39–0.93). Regarding minor ischemic abnormalities, there was no significant association with egg consumption in either women or men. Our findings suggest a gender-specific effect of egg consumption on the presence of major ischemic changes on ECG. Further research is warranted to explore the underlying mechanisms and to inform tailored dietary guidelines for different populations.

Excessive oxidative stress and increased apoptosis are the main culprits to heart damage associated with ischemic heart disease. This study aimed to demonstrate the cardioprotective properties of limonene (LIM), a monoterpenoid compound, in isoproterenol-induced ischemia (ISO-I) in rats.

Forty male Wistar rats were divided into five groups (n=8). Normal saline (1 mL/kg) and LIM at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg were administered for seven days before the induction of ischemia by ISO. Creatine kinase-MB (CK-MB), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capability (TAC), and relative expression of BCL2 and BAX genes underwent measurement.

CK-MB (3.73±0.560 versus 0.888±0.317), CPK (901±72.2 versus 397±33.5), LDH (1992±176 versus 821±94.1), and MDA levels in the serum (65.6±11.0 versus 28.3±4.75) and heart (104±8.70 versus 65.3±7.46) samples significantly increased following ischemia in the treatment groups compared to the control group (P<0.001 for all markers). Ischemia decreased TAC in the heart (324±45.0 versus 588±64.5) and serum (202±23.0 versus 388±45.9) samples compared to the control counterparts (P<0.001 for both samples). ISO-I is associated with a decrease in Bcl-2 (0.880±0.118 versus 1.74±0.178) and an increase in BAX (2.75±0.124 versus 1.08±0.0938) gene expression in comparison to the control group (P<0.001 for both genes). LIM could reverse the aforementioned heart damage-related biomarkers in the serum and heart samples. Finally, LIM improved histopathological disarrangement following ischemia.

The findings revealed that LIM, at least partially due to its antioxidant and anti-apoptotic potentials, exerted cardioprotection against ISO-induced heart ischemia in rats.

 It seems that maternal intervention, which may involve epigenetic mechanisms, can affect cerebral ischemia in offspring. Metformin consumption by the mother activates the AMP-activated protein kinase (AMPK) pathway. Metformin has also induced the AMPK and protected neurons in cerebral ischemia. This study investigates the effect of maternal metformin administration, which activates the AMPK pathway, on cerebral ischemia in offspring.

 Animals were separated into four groups: sham, 2-vessels occlusion (2VO), Met+2VO, Met+compound c (CC)+2VO. Female rats were administrated with metformin at a dose of 200 mg.kg-1 body weight for 2 weeks prior to mating. After the final metformin injection, each female rat was paired with an intact adult male to allow for mating. Sixty-days old offspring underwent cerebral ischemia and then memory-related tests were done.

 Current data revealed that the neurological deficits score was reduced Met+2VO group (P<0.001), and the memory increased (P<0.001) in comparison to the 2VO. The Bcl-2/Bax ratio declined in the metformin group (P<0.001) while the brain-derived neurotropic factor (BDNF), c-fos, p-AMPK/AMPK ratio and Histone H3K9 acetylation in the hippocampus augmented significantly compared to the 2VO group (P<0.001).

 These findings indicated that the metformin intervention via AMPK activation could improve the movement disability, enhance spatial memory, increase neural plasticity, and augment the bioenergetics state and histone acetylation in the hippocampus of the offspring.

Cerebral ischemia/reperfusion (I/R) injury is the most prevalent form of brain stroke, affecting many patients worldwide. It is believed that oxidative stress and inflammation play major roles in the damage that occurs after the initiation of the disease.

Therefore, for the first time, the current study aimed to investigate the neuroprotective effects of bupropion against cerebral I/R damage in a rat model.

Forty male rats were divided into four groups: Control, cerebral I/R, and two diseased groups that received 60 and 100 mg/kg of bupropion. One day after induction of the disease, behavioral tests, including grid walking, novel object recognition, and modified neurological severity score (mNSS), were performed on the rats. The levels of inflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-10, were measured in the rats' brain homogenates. Additionally, the levels of MDA, catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and NO2 - were measured.

Bupropion administration was associated with improved performance in the novel object recognition and grid walking behavioral tests, as well as in the neurological disorder scores, in cerebral I/R rats. Moreover, BCAAO-induced inflammation was reduced by the administration of this drug, evidenced by reduced levels of cytokines IL-1β, TNF-α, and IL-6 and upregulation of IL-10. Additionally, membrane lipid peroxidation was reduced in the cerebral I/R rats receiving 100 mg/kg bupropion, and the level of SOD activity was improved in these animals. Finally, the administration of bupropion prevented the increase in NO2 - levels induced by BCAAO.

In conclusion, bupropion has neuroprotective effects against cerebral I/R damage by reducing inflammation and oxidative stress in the brain.

The purpose of this study was estimate and identify in hospital mortality predictors factors for patients with acute ST elevation myocardial infarction (STEMI). This study is a retrospective cohort study based on data from the Yazd Cardiovascular Diseases Registry (YCDR) from 2015-2018 in Yazd Province, Iran, focusing on hospitalized patients with ST-elevation myocardial infarction (STEMI). The primary outcome was in-hospital mortality in STEMI patients. A total of 1861 patients with STEMI were analyzed. Multivariable logistic regression was used to determine death predictive factors for in-hospital mortality in STEMI patients. The significance level of the model was considered to be 5% and the software was used for analysis. The study included 1,861 patients with STEMI. Among them, 103 (5.5%) individuals died during admission the hospital. After multivariable logistic regression, the following variables were identified as death predictive factors for in-hospital mortality of STEMI: having a history of CVA (OR: 5.6, 95% CI: 2.2-20.3), killip class IV (OR: 6.4, 95%CI: 1.5-11.2), lower ejection fraction (OR: 3.6, 95% CI: 1.2-9.8), lower HDL cholesterol (OR: 1.2, 95% CI: 1.01-2.3), and lower hemoglobin (OR: 1.4, 95% CI: 1.3-2.9). This study found that lower ejection fraction, lower hemoglobin levels, Killip class IV, having a history of CVA, and low HDL cholesterol levels are important death predictive factors for hospital mortality in patients with STEMI. Health policy in STEMI management must consider these factors to improve hospital prognosis.

Liver ischemia-reperfusion (I/R) is the director’s origin of damages in various clinical situations, especially surgery and transplantation. Inflammatory damages are critical because of the chronicity of I/R injuries (I/RI). The hepatoprotective and antiinflammatory properties of silibinin have been reported in different studies. This study aimed to investigate the effect of Silibinin on the expression of the pannexin-1 (Panx1) gene during hepatic I/R.

In this case-control animal study, a total of 32 male Wistar rats (n=8 in each) were surveyed. The animals were randomly assigned into four equal groups as follows: Group 1 (Control): the rats underwent a midline laparotomy with normal saline injection; Group 2 (SILI): the rats received Silibinin (50 mg/kg) after laparotomy; Group 3 (I/R): the rats underwent I/R surgery and received normal saline; and Group 4 (I/R+SILI): the rats received silibinin before ischemia and directly following reperfusion. Blood and liver tissue samples were taken after three hours of reperfusion aftermath 1-hour ischemia to evaluate histological changes, gene expression, and serum markers of hepatic injury.

While the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the I/R group significantly increased compared to the control group (P<0.001), they significantly decreased in the SILI+I/R group (P<0.001). Silibinin ameliorated inflammatory impairments of liver tissue, such as neutrophil and macrophage infiltration and activation, hepatocyte degeneration and vacuolation, hepatic vascular endothelial damage, and sinusoid proliferation in the I/R group. The expression of the Panx1 mRNA during I/R significantly increased compared to the control group (P<0.001), but silibinin reduced the expression (P<0.001).

We witnessed that silibinin reduced liver tissue damages during hepatic I/R. Correcting the expression of the Panx1 gene during I/R is probably one of the mechanisms of anti-inflammatory effects of silibinin.

 Ischemic stroke (IS) is still a major cause of neurological disability. This study aimed to ascertain potential markers closely related to IS diagnosis and treatment and then we examined the neuroprotective effect of N-acetylcysteine (NAC) in a transient cerebral ischemia.

 Male Wistar rats were randomly divided into three groups (n=6), including sham, IR (ischemia-reperfusion), IR+NAC (150 mg/kg, ip; intraperitoneally, 1 hour prior to ischemia and 5 min before reperfusion). The infarct volume was evaluated by 2,3,5-triphenyl tetrazolium chloride staining. H&E and Nissle staining were performed to evaluate cerebral ischemia-reperfusion injury. miR-374a-5p gene expression, MAPK6, NLRP3, smad6, TNF-α, and IL-1β protein levels were determined by Real-time PCR, Western blot, and Elisa in the cerebral cortex exposed to IR.

 Herein, we found that IR increased infarct volume and pathological damage to the cerebral cortex after global cerebral artery occlusion/reperfusion. In addition, miR-374a-5p gene expression decreased, while MAPK6, NLRP3, and smad6 protein expressions increased in the IR group. TNF-α and IL-1β protein levels increased in the ischemic cortex. Treatment with NAC significantly attenuated infarct size, inflammation and reversed aforementioned molecule levels.

 Taken together, these results suggested that ischemic insult can increase infarct size, neuronal damage, and inflammation may in part by modulating miR-374a-5p, MAPK6, NLRP3, and smad6 pathway in the brain cortex after cerebral IR insult and providing new clues to molecular mechanisms and treatment targets in IS. It can be alleviated by NAC as a potential therapy for someone afflicted with ischemia.

Expression of miR-188-5p changes upon experiencing cerebral I/R injury. SENP3 is a predicted target of miR-188-5p. The study aimed to examine the potential mechanism underlying the miR-188-5p mediated enhancement of SUMO2/3 conjugation via targeting SENP3 and alleviation against cerebral I/R injury.

Focal cerebral I/R was established in Sprague–Dawley rats using the MCAO model. The expression of miR-188-5p was modulated through intracerebroventricular (ICV) administration of its mimics or inhibitors. The expression of miR-188-5p, SENP3, and SUMO2/3 was detected using RT-qPCR or western blot analysis. Dual luciferase reporter assays were conducted to demonstrate the targeting effect of miR-188-5p on SENP3 in N2a cells. HE staining and TUNEL staining were performed to evaluate neurocellular morphological changes and detect neurocellular apoptosis, respectively. The extent of neurological deficits was evaluated using mNSS. TTC staining was used to evaluate the infarct area.

In the cerebral ischemic penumbra, the expression of miR-188-5p declined and SENP3 levels increased following I/R. Dual luciferase reporter assays confirmed that miR-188-5p directly acted on SENP3 in N2a cells. As a self-protective mechanism, SUMO2/3 conjugation increased after reperfusion. After ICV administration of miR-188-5p inhibitor, the expression of miR-188-5p was down-regulated, the expression of SENP3 was up-regulated, the SUMO2/3 conjugation decreased, and cerebral I/R injury was exacerbated. However, ICV administration of small hairpin RNA targeting SENP3 partially reversed the effects of the miR-188-5p inhibitor.

MiR-188-5p mitigated cerebral I/R injury by down-regulating SENP3 expression and consequently enhancing SUMO2/3 conjugation in rats.

Importance:

 Ischemic heart disease is the leading cause of death worldwide. In ST-elevation myocardial infarction (STEMI), delaying reperfusion from the onset of chest pain increases the incidence of mortality and morbidity. Prehospital thrombolysis(PHT) has been evaluated in the setting of STEMI. We performed a systematic analysis of studies of PHT in acute STEMI.

The objective of this study was to evaluate the all‑cause mortality benefit in STEMI with PHT during short‑term and long‑term follow‑up. Data Sources: In December 2020, the Cochrane search strategy was used to analyze randomized control trials, nonrandomized control studies, and registry studies in PubMed, EMBASE, Cochrane Library, Google Scholar, ClinicalKey, and Clinical Trial Registries. The search was repeated, and the included studies were updated in June 2023 to include more recent literature. We restricted the analysis to full-text publications in English. Study Selection: Studies using any thrombolytic agent in treating acute myocardial infarction in prehospital and inhospital settings with or without percutaneous Coronary intervention (PCI) were included in the analysis. Selection criteria included patient history and symptoms, electrocardiogram findings, and cardiac markers. Data Extraction: We used the Cochrane Handbook for Systematic Reviews of Interventions for assessing bias, the PRISMA flow diagram to show the process of inclusion and exclusion of studies, and RevMan software to perform meta-analysis. Main Outcomes and Measures: Outcomes include all-cause hospital mortality rate of PHT versus inhospital thrombolysis(IHT), influence of ischemic median time on all‑cause mortality with PHT, and effect of PHT before PCI. The measures must have been observed for a follow‑up period of up to 35 days, 1-year, and 5-years.

Data from 63,814 patients from 32 studies were reviewed. Results indicate a reduction in all‑cause mortality in patients assigned to PHT (odds ratio [OR] −0.68, P < 0.00001) compared to IHT. There was a significant reduction in mortality when thrombolytics were administered before PCI (OR − 0.78, P = 0.0001). The overall survival was better with an ischemic time of <2 h. Mortality was higher with longer ischemic time (3 h and 6 h). Among patients who presented within 2 h of the onset of chest pain, mortality was lower compared to primary PCI (pPCI).

PHT offers faster reperfusion and reduces all‑cause mortality compared to IHT. A strategy of PHT within the first 2‑3 h of ischemic pain followed by PCI (if indicated) could offer better survival than pPCI.

 Stroke is considered as one of the most important causes of emergency medical services (EMS) dispatch worldwide. Stroke is a time-sensitive condition and rapid transport of the patients improves the prognosis. In this study, we described prehospital emergency response times for stroke patients in Isfahan, Iran. 

 In the current cross-sectional descriptive study, suspected stroke patients who were transported by EMS in Isfahan, Iran, from June 2022 to June 2023 were included. The data was extracted from patients’ files. The time interval between the receipt of a call and the EMS arrival at the scene (arrival time), the time interval between on-scene EMS arrival and the ambulance departure to the medical center (stroke scene time), and the time it takes to reach the medical center (transport time) were collected. 

  Overall, 79 patients with a mean age of 71.56 ± 12.03 were included. EMS diagnosed 63 (79.75%) of the patients with a definite diagnosis and 14 (17.72%) with probable stroke. Two false negative results were found. The average arrival time, was 11.56 ± 6.60 minutes, on-scene stroke time was 13.85 ± 7.23 minutes and the average transport time was 11.90 ± 6.08 minutes. The mean total EMS response time was 37.90 ±11.29 minutes. 

 Overall, our study showed that while the EMS transport time is longer than ideal, the total time to transport to the hospital is short enough not to affect the outcome. EMS was also found to be adept at spotting the signs of stroke and rapidly starting the process of treatment.

Acute kidney injury (AKI) is a rapid loss of kidney function that is associated with high morbidity and mortality. Oxidative hazard, inflammation, mitochondrial deterioration and depletion of cellular energy stores, which terminate in organ dysfunction, are the major hallmarks of AKI. The current experimental investigation attempted to evaluate the effects of selenium (Se), a pivotal micronutrient, on the ischemia/reperfusion (IR)-induced kidney damage emphasizing on the biogenesis of mitochondria.

Male Wistar rats (n = 18) were randomly allocated into three groups: sham, IR, and Se + IR. Rats in the last group 1 h before IR induction, were treated with Se (0.5 mg/kg) intraperitoneally. Six hours after reperfusion blood and kidney tissue samples were collected, and animals were euthanized. In addition to the evaluation of biochemical factors and histopathology, the protein levels of sirtuin1 (SIRT-1), and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α) of the kidney tissues were determined via western blotting.

Pre-treatment with Se could significantly improve IR-induced kidney function markers (creatinine and BUN) as well as the pathological alteration in comparison with the IR group (P < 0.05). Moreover, in the Se + IR group, a substantial surge of the Sirt-1 and PGC-1α at the protein level was recorded compared to the IR group.

The results proposed that Se displays a protective role against renal IR injury via up-regulating proteins involved in mitochondrial biogenesis. Due to the pivotal role of mitochondria in renal tubules, these results offer insight into the plausible preventative and/or therapeutic effects of Se against AKI after further studies.

Ovarian torsion is an important gynaecological emergency because it causes ischemia in ovary. Our aim is to research the effects of Hypericum perforatum on p53, TNF-α, CAT, SOD, GSH, PTEN and is haPI3K/Akt/mTOR pathway in ovarian of rats with ischemia reperfusion (I/R) injury.

The study included 56 adult female rats which were allocated to 7 groups; control, ischemia, ischemia 300HP, ischemia 600HP, I/R, I/R 300HP and I/R 600HP. H. perforatum was applied to ischemia 300HP, ischemia 600HP, I/R 300HP and I/R 600HP groups at the dose of 300 mg/kg or 600 mg/kg by oral gavage. Collected ovarian tissues were examined by light microscopy, biochemical and real-time PCR techniques.

In histological examination, the least degeneration was seen in 600HP group among other groups, apart from control group. TUNEL results showed that apoptosis level of other groups was lower than that of ischemia and I/R groups. CAT and GSH levels of I/R 600HP group increased. The highest level of PTEN and mTOR was found in the ischemia group. The Akt level was lower in I/R and I/R 300HP groups but its level was close to that of control and I/R 600HP groups. TNF-α and p53 mRNA expressions in I/R group were increased.

The result of the study showed that H. perforatum (600 mg/kg) had an effect on tissue degeneration, CAT and GSH levels, and also TNF-α and p53 mRNA expressions levels. We suggest that H. perforatum can be considered as an agent to protect against tissues damage during ischemia reperfusion.

Hepatic ischemic post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the interleukin 6-Janus kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver.

Twenty-five rats were randomly divided into 5 groups of (1) sham-operated, (2) IR, (3) IR+hepatic IPOC, (4) IR+tofacitinib (TOFA), and (5) IR+TOFA+hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio.

The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (P<0.001, P<0.05, P<0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR+hepatic IPOC compared with those in the IR group (P<0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC.

It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.

 Ischemia is one of the most common injuries that is usually caused by reduced blood flow to the tissues. Following this incident, the tissue becomes deficient in oxygen and nutrients, and energy production in the affected cells stops, eventually leading to cell damage, but there is also evidence that restoring blood flow to ischemic tissues can lead to extra tissue damage known as Ischemia Reperfusion Injury (IRI). In this study, we reviewed the relationship between vitamin C intake and ischemia/reperfusion injury to investigate the relationship between vitamin C intake and ischemia/reperfusion injury. The keywords “Vitamin C” or “Ascorbic Acid” and “Ischemic” or “Ischemia” and “Reperfusion” were used in this search. The results show that vitamin C has a positive effect on ischemia treatment in the renal tissue, brain, liver, intestine, lung, ovary, pancreas, and skin.

The current study aimed to introduce the key proteins involved in liver ischemia/reperfusion (I/R) injury through protein-protein interaction (PPI) analysis.

Liver transplantation (LT) is a well-known treatment for liver diseases that threaten patients with mortality. LT is a complex operation, and several risks, including liver I/R injury, affect its success. Improving LT requires detection of its molecular mechanism. Experiments have revealed that high throughput methods such as proteomics in combination with bioinformatics are useful tools for analyzing the molecular mechanism of disease.

The differentially expressed proteins (DEPs) involved in liver I/R injury were extracted from the literature. The queried DEPs plus the first 100 neighbors were included in a network through STRING database using Cytoscape software. Degree, betweenness centrality, closeness centrality, and stress were considered to determine the central nodes. The queried DEPs were assessed by action map analysis using the CluePedia application of Cytoscape software. The key proteins were identified by comparing network analysis and action map evaluation results.

Six proteins, namely ALB, INS, GAPDH, CAT, IL6, and TNF, among the added first neighbors were determined as the central first neighbors. MPO, CRP, MMP9, and HMOX1 were selected as central DEPs among the queried proteins. Action map analysis confirmed the PPI findings. The final evaluation revealed that MMP9 in combination with CRP and HMOX1 plays a critical role in liver I/R injury.

The significant role of MMP9 in liver I/R injury was detected in this study. Two central proteins (CRP and HMOX1) were shown to have a regulatory effect on MMP9; CRP activated MMP9, while HMXO1 downregulated it.

Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the β2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.

Reduction of cerebral ischemia-reperfusion injury (IRI)/re-oxygenation injury, is defined as the paradoxical exacerbation of the cellular dysfunction and death, following restoration of the blood flow to previously ischemic tissues. The re-establishment of blood flow is essential to salvage the ischemic tissues. As a result, the treatment of IRI with novel therapies, which have fewer side effects, are of great importance. Therefore, this study aimed to investigate the effects of curcumin nanoparticle (CN) pre-treatment on the cerebral I/R rat model.

In this experimental study, CN was administered to rats orally five days before the bilateral common carotid artery occlusion (BCCAO) and continued for three days. The intensity of oxidative stress, the activities of antioxidant enzymes, glutathione (GSH) content, the activity of mitochondrial enzymes, including succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH), curcumin bioavailability, pERK/ERK expression ratio and TFEB protein were studied. Data analysis was performed using Graphpad Prism V.8 software, one-way analysis of variance (ANOVA) with the statistical package for the social sciences (SPSS V.26 software).

Cerebral IRI-damage significantly increased the oxidative stress (P=0.0008) and decreased the activity of the antioxidant enzymes including catalase (CAT) (P<0.001), super oxide dismutase (SOD) (P<0.001), reduced GSH (P<0.001), mitochondrial enzymes, pERK/ERK expression ratio (P=0.002) and TEFB protein (P=0.005) in rats’ brains. In addition, the pre-treatment of the rats with CN resulted in a decrease in the reactive oxygen species (ROS), and an increase in the activities of antioxidants and mitochondrial enzymes. This in turn up-regulated the pERK/ERK expression ratio and TEFB expression.

CN has neuroprotective effects on the cerebral IRI condition due to its antioxidant properties and is able to overexpress the pERK and TFEB proteins; thus, it can be considered as a suitable treatment option during and after the incidence of stroke.

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel’s sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.