Ischemic Damage Research Articles

Cognitive Interventions in Individuals With Chronic Respiratory Diseases: Protocol for a Systematic Review.

Chronic respiratory diseases (CRDs) may cause reduced oxygen availability to organs and body tissues, leading to an increased risk for ischemic damage, which can result in brain tissue injury. This damage can lead to a myriad of neurological symptoms contributing to cognitive decline. Cognitive interventions may attenuate cognitive deficits in people with CRDs; however, the effects have not yet been systematically summarized in the literature. The purpose of this systematic review is to assess the effects of cognitive interventions (including cognitive behavioral therapy and transcranial brain stimulation) on cognitive function (primary outcome), HRQL, self-management, symptoms, physical activity, physical function, ability to complete activities of daily living (ADLs), hospital admissions, functional capacity, functional performance, psychological and social outcomes, exacerbations, healthcare utilization, and survival in individuals with CRDs. This review will be conducted in accordance with the Cochrane handbook for systematic reviews of interventions and reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Searches will be performed in MEDLINE, Embase, Emcare, PsycINFO, Scopus, and CINAHL. Articles will be included if they focus on the effects of cognitive interventions on adults with CRDs, are published in peer-reviewed journals, and are written in English, French, or Portuguese. Risk of bias will be evaluated with the Cochrane Risk of Bias 2 tool for randomized controlled trials, and the Risk of Bias in Non-randomized Studies of Interventions tool for nonrandomized studies. Meta-analyses will be performed if at least 2 studies provided sufficient data for a specific outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) assessment will be used to evaluate the overall quality of the evidence. This systematic review was initiated in November 2022 and registered with PROSPERO in February 2023, prior to title and abstract screening. Full-text screening of articles will be completed in June 2023. Data extraction and drafting of the manuscript will occur from July 2023 to August 2023, with expected publication in February 2024. This systematic review will summarize the effects of cognitive interventions on cognitive function in people with CRDs. It will guide health care professionals in selecting evidence-based strategies to enhance cognitive well-being and overall health outcomes for individuals with CRDs. Additionally, it will identify research gaps and highlight areas for future exploration, supporting researchers in advancing knowledge in this field. PROSPERO CRD42023396234; https://tinyurl.com/mwjrfbxv. PRR1-10.2196/48235.

S100A8∕A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction.

Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8∕A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8∕A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8∕A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8∕A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.

Когнитивные нарушения при хронической цереброваскулярной патологии и возможности их коррекции на додементных стадиях

Cerebrovascular diseases are among the most frequent nosological forms of modern neurology. One of the most important components of their clinical picture is cognitive impairment. At the same time, the most frequent is the development of mild and moderate cognitive disorders. This is especially true for the initial stages of the disease. The pathogenetic basis of the violation of higher cortical functions is a complex of pathophysiological and pathochemical reactions formed within the cascade of ischemic damage to the brain substance. One of the central places among them is occupied by the development of energy deficiency due to a decrease in ATP synthesis and the formation of oxidative stress. This makes it necessary to prescribe pharmacological drugs that can have a multimodal effect. Among such drugs, idebenone is distinguished, which can stimulate the mitochondrial respiratory chain and, in addition, exhibits antioxidant properties. which has demonstrated its effectiveness in the treatment of pre-segment cognitive impairment in patients with cerebrovascular pathology, especially in the framework of combined administration with drugs having other mechanisms of action.

EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1.

This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism. Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1β, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified. OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation. Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.

Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion.

Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion.

Isoflurane Anesthesia's Impact on Gene Expression Patterns of Rat Brains in an Ischemic Stroke Model.

Ischemic stroke (IS) is one of the most severe brain diseases. Animal models with anesthesia are actively used to study stroke genomics and pathogenesis. However, the anesthesia-related gene expression patterns of ischemic rat brains remain poorly understood. In this study, we sought to elucidate the impact of isoflurane (ISO) anesthesia on the extent of ischemic brain damage and gene expression changes associated with stroke. We used the transient middle cerebral artery occlusion (tMCAO) model under long-term and short-term ISO anesthesia, magnetic resonance imaging (MRI), RNA sequencing, and bioinformatics. We revealed that the volume of cerebral damage at 24 h after tMCAO was inversely proportional to the duration of ISO anesthesia. Then, we revealed hundreds of overlapping ischemia-related differentially expressed genes (DEGs) with a cutoff of >1.5; Padj < 0.05, and 694 and 1557 DEGs only under long-term and short-term anesthesia, respectively, using sham-operated controls. Concomitantly, unique DEGs identified under short-term anesthesia were mainly associated with neurosignaling systems, whereas unique DEGs identified under long-term anesthesia were predominantly related to the inflammatory response. We were able to determine the effects of the duration of anesthesia using isoflurane on the transcriptomes in the brains of rats at 24 h after tMCAO. Thus, specific genome responses may be useful in developing potential approaches to reduce damaged areas after cerebral ischemia and neuroprotection.

Glyoxal in hyperglycaemic ischemic stroke – a cohort study

BackgroundHyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke.MethodsIn 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested.ResultsGlucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids Nε-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal.ConclusionsThe glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.

Combination of acute myocardial infarction and Takotsubo syndrome

A 79-year-old woman was admitted to the emergency department of cardiology after transient loss of consciousness episode and a recorded ventricular tachycardia. The ST segment elevation in I, aVL, V1-V5 leads up to 6 mm and ST-segment depression up to 1 mm in III, aVF were registered at admission. The emergency coronary angiography showed of slowed coronary blood flow without stenosing atherosclerosis. The diagnosis of acute myocardial infarction was based on: 1. The typical progression of ECG: ST elevation resolved and the T wave become inverted; 2. The transient increasing CK up to 439 U/l, CK-MB up to 52 U/l and troponin I up to 5.8 ng/ml; 3. The inclusion of paramagnetic in the myocardium in the anterior wall and septum of LV by the type of ischemic damage. The diagnosis of Takotsubo syndrome based on rapid and complete recovery of contractility and geometry of the left ventricle (LV). At the 2nd day LV ejection fraction was 21%; the dyskinesis, akinesis of the anterior and antero-lateral walls of the left ventricle were registered. At the 7th day the hypokinesis zones was not detected. The article discusses the literature data on the frequency of combination of these diseases and possible pathogenetic mechanisms of this combination.

Successful transplantation of LUCAS device assisted uncontrolled DCD kidneys with prolonged relative warm ischemia time: An underutilized option in North America.

Approximately 25% of deceased donors in the United States are procured in a donation after circulatory death (DCD) setting. Successful transplant outcomes from uncontrolled DCD (uDCD) practices have been reported in multiple European programs. They utilize established protocols for uDCD procurement with normo-thermic or hypothermic regional perfusion to reduce ischemic damage. Further, manual or mechanical chest compressions using extrinsic devices, such as the LUCAS device, are implemented to maintain circulation before organ retrieval. Currently, uDCDs are not a major part of DCD organ utilization in the United States. We report our experience with utilization of kidneys from uDCD with the use of the LUCAS device without normothermic or hypothermic regional perfusion. We transplanted four kidneys from three uDCD donors without utilization of in situ regional perfusion and with prolonged relative warm ischemia time (rWIT) (>100min). All recipients had functional renal allografts and improved renal function after the transplant. To our knowledge, this is the 1st successful series reported in the United States of the utilization of kidneys from uDCDs without the utilization of in situ perfusion to maintain organ preservation with prolonged rWIT.

Neuroprotection of Stem Cells Against Ischemic Brain Injury: From Bench to Clinic.

Neurological injuriescan have numerous debilitating effects on functional status including sensorimotor deficits, cognitive impairment, and behavioral symptoms. Despite the disease burden, treatment options remain limited. Current pharmacological interventions are targeted at symptom management but are ineffective in reversing ischemic brain damage. Stemcell therapy for ischemic brain injury has shown promising preclinical and clinical results and has attracted attention as a potential therapeutic option. Various stem cell sources (embryonic, mesenchymal/bone marrow, and neural stem cells) have been investigated. This review provides an overview of the advances made in our understanding of the various types of stem cells and progress made in the use of these stem cells for the treatment of ischemic brain injuries. In particular, the use of stem cell therapy in global cerebral ischemia following cardiac arrest and in focal cerebral ischemia after ischemic stroke are discussed. The proposed mechanisms of stem cells' neuroprotective effects in animal models (rat/mice, pig/swine) and other clinical studies, different routes of administration (intravenous/intra-arterial/intracerebroventricular/intranasal/intraperitoneal/intracranial) and stem cell preconditioning are discussed. Much of the promising data on stem cell therapies after ischemic brain injury remains in the experimental stage and several limitations remain unsettled. Future investigation is needed to further assess thesafety and efficacy and to overcome the remaining obstacles.

Overexpressing glyoxalase 1 attenuates acute hyperglycemia–exacerbated neurological deficits of ischemic stroke in mice

Stress-induced hyperglycemia (SIH) is associated with poor functional recovery and high mortality in patients with acute ischemic stroke (AIS). However, intensive controlling of blood glucose by using insulin was not beneficial in patients with AIS and acute hyperglycemia. This study investigated the therapeutic effects of the overexpression of glyoxalase I (GLO1), a detoxifying enzyme of glycotoxins, on acute hyperglycemia–aggravated ischemic brain injury. In the present study, adeno-associated viral (AAV)-mediated GLO1 overexpression reduced infarct volume and edema level but did not improve neurofunctional recovery in the mice with middle cerebral artery occlusion (MCAO). AAV-GLO1 infection significantly enhanced neurofunctional recovery in the MCAO mice with acute hyperglycemia but not in the mice with normoglycemia. Methylglyoxal (MG)-modified proteins expression significantly increased in the ipsilateral cortex of the MCAO mice with acute hyperglycemia. AAV-GLO1 infection attenuated the induction of MG-modified proteins, ER stress formation, and caspase 3/7 activation in MG-treated Neuro-2A cells, and reductions in synaptic plasticity and microglial activation were mitigated in the injured cortex of the MCAO mice with acute hyperglycemia. Treatment with ketotifen, a potent GLO1 stimulator, after surgery, alleviated neurofunctional deficits and ischemic brain damage in the MCAO mice with acute hyperglycemia. Altogether, our data substantiate that, in ischemic brain injury, GLO1 overexpression can alleviate pathologic alterations caused by acute hyperglycemia. Upregulation of GLO1 may be a therapeutic strategy for alleviating SIH-aggravated poor functional outcomes in patients with AIS.

Features of Ocular Blood Flow in Malignant Arterial Hypertension of Renal Origin

Color Doppler imaging allows a detailed non-invasive assessment of the state of blood flow in the retrobulbar vessels in patients with various vascular pathologies. Malignant hypertension (MH) is a clinical syndrome characterized by severe diastolic arterial hypertension (140 mm Hg or more), leading to ischemic damage to various organs — kidneys, heart, brain, eyes. Patients with MH often present with thrombotic microangiopathy (TMA), a rare life-threatening condition characterized by multiple systemic thromboses of the microvasculature.Purpose: to assess the state of blood flow in retrobulbar vessels by color Doppler imaging in TMA associated with MH.Methods: 10 patients (20 eyes) (age 43.5 ± 6.2 years) with TMA associated with MH underwent a study of the state of blood flow in the vessels of the retrobulbar space by color Doppler imaging. Qualitative and quantitative analyzes of retinal and choroidal circulation were assessed.Results. Analysis of the Doppler spectrum of blood flow in TMA associated with MH revealed a statistically significant increase in maximum systolic (Vsyst) and finale diastolic blood flow velocity (Vdiast) in the ophthalmic artery (OA), as well as Vsyst in the medial short posterior ciliary arteries (SPCA), compared with the control group (p &lt; 0.05). In 2 patients (20 %) of the study group, a significant bilateral decrease in the diastolic component of the spectrum was found up to the isoline (Vdiast = 0) and a maximum increase in the peripheral resistance index (RI = 1.0). Statistically significant correlations were found between some laboratory parameters of blood serum (hemoglobin, lactate dehydrogenase, creatinine), as well as the estimated glomerular filtration rate and hemodynamic parameters in the central retinal artery (CRA), lateral (SPCA) and OA (p &lt; 0.05).Conclusion. The results of the study of ocular hemodynamics using color Doppler imaging in TMA associated with MH are presented for the first time. TMA associated with MH is characterized by a statistically significant increase in the maximum systolic blood flow velocity in the OA and SPCA with the development of an ischemic state in the retinal and choroidal microcirculation in some patients. An increase in TMA activity in MH leads to a change in the microcirculation of the retina and choroid of an ischemic nature. An increase in blood creatinine in patients with TMA with MH is statistically significantly associated with a decrease in systolic blood flow velocity in the CRA.

Astragaloside IV ameliorates cerebral ischemic damage by restraining adenosine monophosphate-activated protein kinase/mTOR-triggered autophagic process and apoptotic activity in neurons

Astragaloside IV is a natural saponin purified from Astragalus membranaceus that exerts a promising effect on Alzheimer’s disease (AD). This study explored its effects on cerebral ischemic injury. SD rats were randomized into sham-operation group, Vehicle (MCAO) group and Astragaloside IV groups (25, 50 and 100 mg/kg, respectively), followed by analysis of neurological deficit, brain edema, infarct volume and neuronal apoptosis. In addition, autophagy was also monitored using an electron microscope. Finally, the functional mechanism for Astragaloside IV was studied via Western-blotting. Astragaloside IV can ameliorate brain ischemia/reperfusion injury and consequent neurological malfunction. The induction of autophagy is a participant in the protective mechanism for SH-SY5Y cells against brain ischemia/reperfusion damage. Additionally, Astragaloside IV can trigger autophagy by manipulating AMPK/mTOR signal pathway. For SH-SY5Y cells, Astragaloside IV ameliorates oxygen-glucose deprivation-reoxygenation damage via restraining of AMPK/mTOR-triggered autophagic process and mitochondria-mediated apoptotic activity. In conclusion, Astragaloside IV can execute a neuroprotective effect on cerebral ischemia, implying that it might be a promising candidate drug in the therapy and prophylaxis of ischemic stroke.

A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage.

Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2+ cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation.

Ultra Sonographic Study of Kidney Changes Following Experimental Cryogenic Partial Nephrectomy in a Rabbit Model

Background and Objective: Treatment of some limited kidney neoplasms is a partial kidney resection called a partial nephrectomy. One of the concerns in partial nephrectomy is severe and uncontrolled hemorrhage that sometimes results in kidney removal. Cryosurgery is one of the less invasive methods for the management of small kidney lesions, during which the controlled freezing of unwanted tissues will eventually lead to necrosis and gradual destruction of the lesion.The advantages of the cryosurgery method are easy implementation, no thermal ischemia damage during the operation, and no need to cut and suture the kidney parenchyma. Materials and Methods: In this experimental intervention research, the caudal pole of the left kidney of 9 adult female rabbits was subjected to cryogenic partial nephrectomy through a lateral laparotomy. Rabbits were evaluated by ultrasound on 1, 3, 7, 14, 21, and 28 days after surgery to record and observe the extent of kidney damage and healing in the Sagittal and Dorsal sections. Several parameters, such as kidney length dimensions, size of the caudal cortex, and cranial cortex of the kidney, were measured and recorded. Results: Kidney length on days 1, 21, and 28 was significantly less than day 0. On the 7th day after surgery, 2 separate areas, damaged and frozen necrotic tissue (caudal cortex) and healthy and normal kidney tissue were visible. The size of the caudal cortex from day 14 onwards was significantly less than day 0. The process of significant changes in the caudal cortex of the kidney started from day 14 of surgery and the border between dead and living tissue (Line of Demarcation) was distinguishable as a transition zone. On the 21st day after surgery, both the length of the kidney and the caudal cortex decreased significantly compared to day 0. Gradual loss of the caudal pole of the kidney (caudal cortex, the place where cryosurgery was performed directly) showed the applicability of cryosurgery in surgeries during which the tumor was removed (tumor ablation). On the 28th day after surgery, due to gradual necrosis and the loss of the caudal pole of the kidney, the kidney looked like a bitten apple, and the results of changes in the dimensions of the kidney (caudal cortex and length of the kidney) indicated necrosis of the caudal pole of the kidney, which finally led to the shrinking of the kidney. Conclusion: Ultrasonographic study of kidney injury and healing showed that cryosurgery, in addition to tumor ablation, would also have the ability to remove peripheral tissues (partial nephrectomy).

Intranasal erythropoietin protects granular cells and reduces astrogliosis in the dentate gyrus after ischemic damage, an effect associated with molecular changes in erythropoietin and its receptor

Within the hippocampus, the CA1 and dentate gyrus (DG) regions are considered the most and the least susceptible to damage by cerebral ischemia, respectively. In addition, it has been tested that rHuEPO exhibits neuroprotective properties. This work investigates the effect of different intranasal doses of rHuEPO, applied in different ischemic post-damage times in the DG, and the effect of the rHuEPO on astroglial reactivity after cerebral ischemia. Additionally, an effective dose for neuroprotection and an administration time was used to evaluate gene and protein expression changes of EPO and EPOR in the DG region. We observed a considerable loss of cells on the granular layer and an increased number of GFAP immunoreactive cells in this region only 72 h after the onset of ischemia/damage. When rHuEPO was administered, the number of morphologically abnormal cells and immunoreactivity decreased. In the analysis of protein and gene expression, there is no correlation between expression level of these molecules, although the rHuEPO amplifies the response to ischemia of EPO and EPOR gene for each evaluated time; in the case of the protein only at 2 h this effect was observed. We demonstrated the susceptibility of the DG to ischemia; so granular cells damage was observed, moreover of the astrocytic response, which is accompanied by molecular changes in signaling mediated by rHuEPO intranasal administration.

Post-Ischemic Permeability of the Blood-Brain Barrier to Amyloid and Platelets as a Factor in the Maturation of Alzheimer's Disease-Type Brain Neurodegeneration.

The aim of this review is to present evidence of the impact of ischemic changes in the blood-brain barrier on the maturation of post-ischemic brain neurodegeneration with features of Alzheimer's disease. Understanding the processes involved in the permeability of the post-ischemic blood-brain barrier during recirculation will provide clinically relevant knowledge regarding the neuropathological changes that ultimately lead to dementia of the Alzheimer's disease type. In this review, we try to distinguish between primary and secondary neuropathological processes during and after ischemia. Therefore, we can observe two hit stages that contribute to Alzheimer's disease development. The onset of ischemic brain pathology includes primary ischemic neuronal damage and death followed by the ischemic injury of the blood-brain barrier with serum leakage of amyloid into the brain tissue, leading to increased ischemic neuronal susceptibility to amyloid neurotoxicity, culminating in the formation of amyloid plaques and ending in full-blown dementia of the Alzheimer's disease type.

Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats.

To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats. The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored. Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 β and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01). Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

Photochemicallly Induced Thrombosis as a Model of Ischemic Stroke

Better understanding of ischemic brain injury mechanisms is important for the development and improvement of diagnostic and therapeutic modalities for management of ischemic stroke. As experimental studies are on demand, there’s a need for relevant models of focal brain lesions. Photochemically induced thrombosis remains one of the most popular models of ischemic stroke.The purpose of the reviewis to consider the pathogenesis and applicational relevance of the photochemical thrombosis in ischemic stroke modeling.Material and methods.The information was searched using PubMed and Google Scholar databases and keywords «photothrombotic stroke» without language restrictions. 74 papers out of more than 600 sources were found the most relevant for the purpose of this review and selected for the analysis. Of these, more than 50% have been published in the last five years. The criterion for excluding a source was an inconsistency with the objectives of the review and low information content.Results.We outlined a variety of features in modeling photothrombotic stroke, analyzed the advantages and disadvantages of the model, presented data on current method’s modifications, as well as approaches to evaluation of brain lesions in ischemic stroke induced by photothrombosis, and summarized information about the mechanisms of brain damage induced in this model.Conclusion.Several advantages of the photothrombotic stroke model, such as low invasiveness, high reproducibility, inherent control of brain infarction volume and low mortality, determine its active use in experimental studies of ischemic stroke. Pathological processes in the brain modeled by photochemical thrombosis are similar to the processes occurring in acute ischemic cerebral circulation events. Therefore, this model provides insights into cellular and molecular mechanisms of ischemic brain damage, and can be used for developing novel therapeutic approaches for management of ischemic stroke.

Experimental Study of Neuroprotective Properties of Inhaled Argon-Oxygen Mixture in a Photoinduced Ischemic Stroke Model

Acute ischemic stroke is a serious problem for healthcare systems worldwide. Searching for the optimal neuroprotector is a contemporary challenge. Various studies have demonstrated neuroprotective properties of argon in ischemic brain damage models. However, the published data are inconsistent.The aim of the study was to evaluate the effect of 24-hour argon-oxygen mixture (Ar 70%/O₂ 30%) inhalation on the severity of neurological deficit and the extent of brain damage in rats after a photoinduced ischemic stroke. Material and methods. The experiments were carried out on male Wistar rats weighing 430–530 g (N=26). Focal ischemic stroke was modeled in the sensorimotor cortex of the rat brain using photochemically induced vascular thrombosis. The animals were randomly divided into 3 groups: sham procedure + N₂ 70%/O₂ 30% inhalation (SP, N=6); stroke + N₂ 70%/O₂ 30% inhalation (Stroke, N=10); Stroke + Ar 70%/O₂ 30% inhalation (Stroke+iAr, N=10). The limb placement test (LPT) was used for neurological assessment during 14 days. Additionally, on day 14 after the stroke, brain MRI with lesion size morphometry was performed. Summarized for days 3,7 and 14 LPT scores were lower in the Stroke and Stroke + iAr groups as compared to the SP group.Results. Statistically significant differences in LPT scores between SP, Stroke, and Stroke+iAr groups were revealed on day 3 post-stroke: (scores: 14 (13; 14), 6.5 (4; 8), and 5 (3; 8), respectively, P=0.027). However, there was no statistical difference between the Stroke and Stroke+iAr groups.Conclusion. 24-hour inhalation of argon-oxygen mixture (Ar 70%/O₂ 30%) after stroke does not reduce the extent of brain damage or the severity of neurological deficit.