Artery Occlusion Research Articles

Intranasal application of diluted saline alleviates ischemic brain injury in association with suppression of vasopressin neurons.

Cerebral swelling and brain injury in ischemic stroke are closely related to increased vasopressin (VP) secretion. How to alleviate ischemic brain injury by suppressing VP hypersecretion through simply available approaches remains to be established. Using a rat model of middle cerebral artery occlusion (MCAO), testing effects of intranasal application of 0.09% NaCl (IAL) on brain damages, VP neuronal activity, synaptic inputs, astrocytic plasticity, olfactory bulb (OB) activity in immunohistochemistry, patch-clamp recording, Western blotting and co-immunoprecipitation. IAL reduced MCAO-evoked neurological disorders, brain swelling, injury and loss of neurons, increase in c-Fos expression and excitation of supraoptic VP neurons. The effects of IAL on VP neurons were associated with its suppression of MCAO-evoked increase in the frequency of excitatory synaptic inputs and decrease in the expression of glial fibrillary acidic protein (GFAP) filaments around VP neurons. MCAO and IAL also caused similar but weaker reactions in putative oxytocin neurons. In the OB, MCAO also increased the firing rate of mitral cells in the lesioned side, which was reduced by IAL. Direct hypotonic challenge of OB slices increased the expression of glutamine synthetase and GFAP filaments in the glomerular bodies while reducing the firing rate of mitral cells. Blocking aquaporin 4 activity in the supraoptic and paraventricular nuclei in the MCAO side blocked MCAO-evoked VP increase and brain damages. IAL reduces ischemic stroke-evoked brain injury in association with suppressing VP neuronal activity through reducing excitatory synaptic inputs and astrocytic process retraction, which likely result from reducing mitral cell activation.

Acute lower limb ischemia caused by repeat deployment of vascular closure device.

Vascular closure devices are used to facilitate faster hemostasis and earlier ambulation, improve patient comfort, and reduce length of hospital stay after percutaneous endovascular procedures. However, their use may rarely be associated with limb ischemia due to endothelial damage and arterial thrombosis. This report illustrates the case of a patient who experienced acute lower limb ischemia due to superficial femoral artery occlusion caused by repeat closure with Angio-Seal vascular closure device within 30 days in a small-caliber superficial femoral artery. The patient was surgically treated by vascular repair with a synthetic graft, and remains symptom-free in 3-year follow-up. Repeat deployment of vascular closure devices in the same access site within a period of 30 days may cause acute limb ischemia due to arterial thrombosis, especially in patients with small-caliber arteries, even in the absence of evident risk factors.

Predicting coronary artery occlusion risk from noninvasive images by combining CFD-FSI, cGAN and CNN

Wall Shear Stress (WSS) is one of the most important parameters used in cardiovascular fluid mechanics, and it provides a lot of information like the risk level caused by any vascular occlusion. Since WSS cannot be measured directly and other available relevant methods have issues like low resolution, uncertainty and high cost, this study proposes a novel method by combining computational fluid dynamics (CFD), fluid-structure interaction (FSI), conditional generative adversarial network (cGAN) and convolutional neural network (CNN) to predict coronary artery occlusion risk using only noninvasive images accurately and rapidly. First, a cGAN model called WSSGAN was developed to predict the WSS contours on the vessel wall by training and testing the model based on the calculated WSS contours using coupling CFD-FSI simulations. Then, an 11-layer CNN was used to classify the WSS contours into three grades of occlusions, i.e. low risk, medium risk and high risk. To verify the proposed method for predicting the coronary artery occlusion risk in a real case, the patient’s Magnetic Resonance Imaging (MRI) images were converted into a 3D geometry for use in the WASSGAN model. Then, the predicted WSS contours by the WSSGAN were entered into the CNN model to classify the occlusion grade.

Posttraumatic acute myocardial infarction. Is angioplasty of an occluded artery always the best option? Always be ready for alternative scenarios.

Posttraumatic acute myocardial infarction. Is angioplasty of an occluded artery always the best option? Always be ready for alternative scenarios.

Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging.

Global and regional cerebral blood flow (CBF) changes in patients with unilateral internal carotid artery occlusion (ICAO) are unclear when the dual post-labeling delays (PLD) arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique is used. Manual delineation of regions of interest for CBF measurement is time-consuming and laborious. To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique. Twenty hospitalized patients with ICAO and sex- and age-matched controls were included in the study. Regional CBF was measured by Dr. Brain's ASL software. The present study evaluated differences in global, middle cerebral artery (MCA) territory, anterior cerebral artery territory, and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions (including the caudate nucleus, lentiform nucleus, insula ribbon, internal capsule, and M1-M6) and brain lobes (including frontal, parietal, temporal, and insular lobes) between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s. When comparing CBF between ICAO patients and controls, the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s; the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s, and it was lower in 9 brain regions at PLD 2.5 s; the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s. The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s. The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions, whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions. The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s, and in M6 at PLD 2.5 s. Unilateral ICAO results in hypoperfusion in the global and MCA territories, especially in the ASPECTS area. Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Engineering hirudin encapsulation in pH-responsive antioxidant nanoparticles for therapeutic efficacy in ischemic stroke model mice

This study introduces a novel pH-sensitive, hirudin-loaded antioxidant nanoparticle (HD@iNanoAOX) aimed at addressing the challenges of hirudin's short half-life and hemorrhagic transformation. HD@iNanoAOX was engineered to safeguard and prolong hirudin's bioactivity by encapsulating it within antioxidative nanoparticles, facilitating its gradual release in acidic environments. The efficacy of this approach was validated through both ex vivo and in vivo experiments. Ex vivo thrombolytic assays demonstrated that HD@iNanoAOX maintained effective clot lysis activity under acidic conditions. In vivo assessments revealed that HD@iNanoAOX significantly prolonged hirudin's half-life and reduced cerebral infarct volume in a mouse model of middle cerebral artery occlusion (MCAO). Furthermore, HD@iNanoAOX treatment mitigated cerebral oxidative stress, suppressed hemorrhagic transformation, and prevented blood-brain barrier (BBB) disruption. These findings suggest that the combined thrombolytic and antioxidative properties of HD@iNanoAOX offer a promising therapeutic approach for ischemic stroke. Nonetheless, further research is warranted to optimize the formulation and assess its safety and efficacy in clinical settings.

Successful coronary angioplasty of a spontaneous occlusion of the conus artery causing a ST-segment elevation myocardial infarction and electrical storm

BackgroundConus artery occlusion is a rare life-threatening event, typically secondary to iatrogenic etiology, and is treated mainly with conservative therapy and/or balloon angioplasty without stenting. However, treatment remains challenging.Case presentationWe report the case of a 60-year-old man with a known history of coronary artery disease presenting with multiple internal defibrillator cardioversions due to an electrical storm (recurrent ventricular fibrillation). The coronary angiography showed an acute occlusion of the conus artery arising from the proximal segment of the right coronary artery, treated by percutaneous transluminal coronary angioplasty with stenting (drug-eluting stent) without any serious complications.ConclusionsTo our knowledge, this is the first case in the literature where a non-iatrogenic occlusion of the conus artery causing a ST-segment elevation myocardial infarction and electrical storm was treated with percutaneous coronary intervention with drug-eluting stenting.Graphical abstract

Preparation of cubic liquid crystal nanoparticles of puerarin and its protective effect on ischemic stroke

The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).

Revascularization of superior mesenteric artery occlusion via the arc of Buhler: A case report and literature review.

To report revascularization of a superior mesenteric artery (SMA) ostial occlusion via the Arc of Buhler. A 62-year-old female presented with 2 months of recurrent abdominal distension and postprandial pain. Computed tomography angiography (CTA) revealed ostial occlusion of the SMA with distal perfusion via the Arc of Buhler (connecting the celiac trunk and SMA). Conventional endovascular techniques failed. A 0.014 guidewire was passed retrograde through the occlusion via the Arc of Buhler. The guidewire was captured from the femoral sheath and balloon angioplasty with stent placement was performed. The patient had complete symptom resolution post-procedure. Retrograde revascularization via the Arc of Buhler is an effective method for treating the initial segment occlusion of the SMA.

Bipolar radiofrequency ablation of refractory ventricular arrhythmias: results from a multicentre network.

Advanced ablation strategies are needed to treat ventricular tachycardia (VT) and premature ventricular complexes (PVC) refractory to standard unipolar radiofrequency ablation (Uni-RFA). Bipolar radiofrequency catheter ablation (Bi-RFA) has emerged as a treatment option for refractory VT and PVC. Multicentre registry data on the use of Bi-RFA in the setting of refractory VT and PVC are lacking. The aim of this Bi-RFA registry is to determine its real-world safety, feasibility, and efficacy in patients with refractory VT/PVC. Consecutive patients undergoing Bi-RFA at 16 European centres for recurring VT/PVC after at least one standard Uni-RFA were included. Second ablation catheter was used instead of a dispersive patch and was positioned at the opposite site of the ablation target. Between March 2021 and August 2024, 91 patients underwent 94 Bi-RFA procedures (74 males, age 62 ± 13, and prior Uni-RFA range 1-8). Indications were recurrence of PVC (n = 56), VT (n = 20), electrical storm (n = 13), or PVC-triggered ventricular fibrillation (n = 2). Procedural time was 160 ± 73 min, Bi-RFA time 426 ± 286 s, and mean Uni-RFA time 819 ± 697 s. Elimination of clinical VT/PVC was achieved in 67 (74%) patients and suppression of VT/PVC in a further 10 (11%) patients. In the remaining 14 patients (15%), no effect on VT/PVC was observed. Three major complications occurred: coronary artery occlusion, atrioventricular block, and arteriovenous fistula. Follow-up lasted 7 ± 8 months. Nineteen patients (61%) remained VT free. ≥80% PVC burden reduction was achieved in 45 (78%). These real-world registry data indicate that Bi-RFA appears safe, is feasible, and is effective in the majority of patients with VT/PVC.

Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke.

The contraction and subsequent death of brain pericytes may play a role in microvascular no-reflow following the reopening of an occluded artery during ischemic stroke. Mammalian target of rapamycin (mTOR) inhibition has been shown to reduce motility/contractility of various cancer cell lines and reduce neuronal cell death in stroke. However, the effects of mTOR inhibition on brain pericyte contraction and death during ischemia have not yet been investigated. Cultured pericytes exposed to simulated ischemia for 12 h in vitro contracted after less than 1 h, which was about 7 h prior to cell death. Rapamycin significantly reduced the rate of pericyte contraction during ischemia; however, it did not have a significant effect on pericyte viability at any time point. Rapamycin appeared to reduce pericyte contraction through a mechanism that is independent of changes in intracellular calcium. Using a mouse model of middle cerebral artery occlusion, we showed that rapamycin significantly increased the diameter of capillaries underneath pericytes and increased the number of open capillaries 30 min following recanalisation. Our findings suggest that rapamycin may be a useful adjuvant therapeutic to reduce pericyte contraction and improve cerebral reperfusion post-stroke.

Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling.

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our prior research has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17-20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the gene) were subjected to a 60-min middle cerebral artery occlusion (MCAO). Gene floxed females (two alleles) and males (one allele) were included as controls. Infarct volume and behavioral deficits were quantified 3 days after stroke. Immune responses including microglial activation and infiltration of peripheral leukocytes in the ischemic brain were assessed by flow cytometry. Epigenetic modification of IRF5/4 by Kdm6a/5c were analyzed by CUT&RUN assay. The demethylation of H3K27Me3 by kdm6a increased IRF5 transcription; meanwhile Kdm5c demethylated H3K4Me3 to repress IRF5. Both Kdm6a fl/fl and Kdm5c fl/fl mice had worse stroke outcomes compared to fl/y and CKO mice. Gene floxed females showed more robust expression of CD68 in microglia, elevated brain and plasma levels of IL-1β or TNF-α, after stroke. We concluded that IRF5 signaling plays a critical role in mediating the deleterious effect of Kdm6a; whereas Kdm5c's effect is independent of IRF5.

Uncommon culprit artery leading to atypical de winter electrocardiographic changes: a case report

BackgroundA subset of patients with acute coronary artery occlusion requiring emergency revascularization, does not present with the typical ECG features of ST-segment elevation myocardial infarction (STEMI).Timely identification of these atypical presentations is crucial.Case presentationThis report describes a 55-year-old male patient who was admitted to the emergency department with chest pain. The electrocardiogram (ECG) recorded atypical de Winter electrocardiographic changes and their evolution.ResultsCoronary angiography confirmed the occlusion of the second diagonal branch (D2). The patient’s condition improved after D2 balloon angioplasty.ConclusionDe Winter electrocardiographic changes can also be observed in D2 occlusions and may present with milder manifestations. Timely recognition of these changes holds significant clinical value.

Central Retinal Artery Occlusion Following Intralesional Triamcinolone Injection for IgG4-related Orbital Disease.

The risk of blindness associated with periocular and facial injections is well documented. Previous cases describing vision loss following a recent periocular or facial injection have emphasized the importance of facial "danger zones." To date, the literature suggests that nearly half of all cases of central retinal artery occlusion in the setting of a recent periocular or facial injection involve an injection in or around the nose. Here, the authors report the second known case of central retinal artery occlusion following a triamcinolone injection to the lacrimal gland. A 30-year-old female with a diagnosis of IgG4-related disease underwent lacrimal gland debulking with an intralesional steroid injection. She noted OD vision loss immediately after surgery, with posterior segment examination demonstrating retinal whitening with a cherry-red spot and intra-arterial yellow-white plaques. This case serves as a reminder to clinicians regarding the risk of iatrogenic embolism following triamcinolone injections around the face with special attention drawn to the lacrimal gland.

Performance of An Automated Algorithm in Large and Medium Vessel Occlusion Detection: A Real-World Experience.

Fast, accurate detection of large (LVO) and medium vessel occlusion (MeVO) is critical for triage and management of acute ischemic stroke. Multiple AIbased software products are commercially available. However, their strengths and limitations for detection of vessel occlusion in the context of expanding indications for mechanical thrombectomy are not entirely understood. We aimed to investigate the performance of a fully automated commercial detection algorithm to identify large and medium vessel occlusions in Code Stroke patients. We utilized a single-center, institutional, retrospective registry of all consecutive code stroke patients with CTA and automated processing using Viz.ai presenting at a comprehensive stroke center between March 2020 and February 2023. LVO was categorized as anterior LVO (aLVO), defined as occlusion of the intracranial internal cerebral artery or M1-middle cerebral artery (MCA), and posterior LVO (pLVO), defined as occlusion of the basilar artery or V4-vertebral artery. MeVO was defined as occlusion of the M2-MCA, A1/A2-anterior cerebral artery, or P1/P2-posterior cerebral artery. Reports from 12 board-certified radiologists were considered the gold standard. We analyzed the performance of the automated algorithm using STARD guidelines. Our primary outcome was accuracy of anterior LVO (aLVO) by the software. Secondary outcomes were accuracy of the software to detect three additional categories: all LVO (aLVO and pLVO), aLVO with M2-MCA, and aLVO with MeVO. Of 3,590 code stroke patients, 3,576 were technically sufficient for analysis by the automated software (median age 67 years; 51% female; 68% White), of which 616 (17.2%) had vessel occlusions. The respective sensitivity and specificity for all four pre-specified categories were: aLVO: 91% (87-94%), 93% (92-94%); all LVO: 73% (68-77%), 92% (91-93%); aLVO with M2-MCA:74% (70-78%), 93% (92-94%); aLVO with all MeVO: 65% (61-69%), and 93% (92-94%). The automated algorithm demonstrated high accuracy in identifying anterior LVO with lower performance for pLVO and MeVO. It is crucial for acute stroke teams to be aware of the discordance between automated algorithm results and true rates of LVO and MeVO for timely diagnosis and triage. LVO = large vessel occlusion; aLVO = anterior large vessel occlusion; pLVO = posterior large vessel occlusion; MeVO = medium vessel occlusion; EVT= endovascular thrombectomy; AI = artificial intelligence; ACA = anterior cerebral artery; PCA = posterior cerebral artery; BA = basilar artery; VA = vertebral artery.

Vascular changes in the retinal capillary network in fellow eye of the patients with central retinal artery occlusion.

We aimed to evaluate the retinal vascular changes in the superficial and deep retinal vascular networks in the fellow eye of patients with central retinal artery occlusion (CRAO) and compare them with controls using optical coherence tomography angiography (OCT-A). In a cross-sectional study, 27 patients with CRAO and 189 normal controls were included. Ophthalmic examination and OCT-A images were performed on all participants. The total vascular density of the superficial capillary network in the 6-mm scan was significantly lower in the fellow eye of patients with CRAO than in the control group (p = 0.02). No significant difference was observed in the FAZ area of the affected eyes and their fellow eyes compared with the controls. Total vascular density at 300 microns around the fovea was lower in the fellow eye compared with the control group (p = 0.034). The retinal vascular network changes in the fellow eyes of patients with CRAO suggest that persistent microvascular changes may be present before the onset of CRAO. This finding indicates that such changes could serve as an early diagnostic window for systemic vascular changes before catastrophic vascular events occur.

Protein kinase N1 deficiency results in upregulation of cerebral energy metabolism and is highly protective in in vivo and in vitro stroke models

Background and aimWe recently identified protein kinase N1 (PKN1) as a master regulator of brain development. However, its function in the adult brain has not been clearly established. In this study, we assessed the cerebral energetic phenotype of wildtype (WT) and global Pkn1 knockout (Pkn1−/−) animals under physiological and pathophysiological conditions. MethodsCerebral energy metabolism was analyzed by 13C6-glucose tracing in vivo and real time seahorse analysis of extracellular acidification rates as well as mitochondrial oxygen consumption rates (OCR) of brain slice punches in vitro. Isolated WT and Pkn1−/− brain mitochondria were tested for differences in OCR with different substrates. Metabolite levels were determined by mass spectrometric analysis in brain slices under control and energetic stress conditions, induced by oxygen-glucose deprivation and reperfusion, an in vitro model of ischemic stroke. Differences in enzyme activities were assessed by enzymatic assays, western blotting and bulk RNA sequencing. A middle cerebral artery occlusion stroke model was used to analyze lesion volumes and functional recovery in WT and Pkn1−/− mice. ResultsPkn1 deficiency resulted in a remarkable upregulation of cerebral energy metabolism, in vivo and in vitro. This was due to two separate mechanisms involving an enhanced glycolytic flux and higher pyruvate-induced mitochondrial OCR. Mechanistically we show that Pkn1−/− brain tissue exhibits an increased activity of the glycolysis rate-limiting enzyme phosphofructokinase. Additionally, glucose-1,6-bisphosphate levels, a metabolite that increases mitochondrial pyruvate uptake, were elevated upon Pkn1 deficiency. Consequently, Pkn1−/− brain slices had more ATP and a greater accumulation of ATP degradation metabolites during energetic stress. This translated into increased phosphorylation and activity of adenosine monophosphate (AMP)-activated protein kinase (AMPK) during in vitro stroke. Accordingly, Pkn1−/− brain slices showed a post-ischemic transcriptional upregulation of energy metabolism pathways and Pkn1 deficiency was strongly protective in in vitro and in vivo stroke models. While inhibition of mitochondrial pyruvate uptake only moderately affected the protective phenotype, inhibition of AMPK in Pkn1−/− slices increased post-ischemic cell death in vitro. ConclusionThis is the first study to comprehensively demonstrate an essential and unique role of PKN1 in cerebral energy metabolism, regulating glycolysis and mitochondrial pyruvate-induced respiration. We further uncovered a highly protective phenotype of Pkn1 deficiency in both, in vitro and in vivo stroke models, validating inhibition of PKN1 as a promising new therapeutic target for the development of novel stroke therapies.

Catheter-Directed Thrombolysis in the Management of Thrombotic Peripheral Artery Occlusions-Acute and Mid-Term Clinical Outcomes.

Objectives: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) with the recombinant tissue plasminogen activator (rt-PA) in all patients with symptomatic peripheral artery disease in real world practice. Methods: Consecutive patients treated with CDT between January 2013 and December 2020 were included in this retrospective analysis. The primary endpoint was the rate of serious adverse events (SAEs) until discharge. Secondary endpoints included interventional success, predictors for SAEs, bleeding and reperfusion edema/compartment syndrome, limb salvage, and clinical outcomes including target lesion revascularization rate (TLR). Results: Overall, 1238 patients were treated with CDT. SAEs occurred in 511 (41.3%) of the patients, 314 (25.4%) being bleeding complications. There were 95 cases of reperfusion edema/compartment syndrome. Forty-two patients underwent amputation and 33 patients (2.7%) died. CDT was successful in 1177 cases (95.1%). Multivariate logistic regression analysis identified age, abciximab and alprostadil usage, and lysis duration as predictors for SAEs and the use of abciximab as a predictor of reperfusion edema/compartment syndrome. Predictors for bleeding were age, alprostadil usage, and lysis duration. At 12 and 24 months, the limb salvage rate was 91.6% and 88.8%, and TLR rate was 46% and 57.2%, respectively. Conclusions: CDT is an effective endovascular method for the treatment of thrombotic peripheral artery occlusions but is associated with a high complication rate. For SAEs in general and bleeding specifically, increasing age, alprostadil use, and lysis duration were independent risk factors.

Astragaloside IV plays a neuroprotective role by promoting PPARγ in cerebral ischemia-reperfusion rats

Cerebral ischemia-reperfusion injury (CIRI) usually occurs during the treatment phase of ischemic disease, which is closely related to high morbidity and mortality. Promoting neurogenesis and synaptic plasticity are effective neural recovery strategies for CIRI. Astragaloside IV (AS-IV) has been shown to play a neuroprotective role in some neurological diseases. In the current study, we evaluated the effect and possible mechanism of AS-IV in CIRI rats. The middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats to simulate the occurrence of human CIRI. First, we determined the cerebral injury on the 1st, 3rd, 5th and 7th day after cerebral ischemia-reperfusion (I/R) surgery by neurological deficit detection, TTC staining, TUNEL staining and Western blot analysis. Furthermore, rats were pre administered with AS-IV and then subjected to cerebral I/R surgery. Brains were collected on the 3rd day to evaluate the neuroprotective effect of AS-IV. Our results showed that on the 3rd day after I/R, the neurological impairment score and infarct volume were highest, the levels of apoptosis and expression of Caspase3 and Bax reached the peak. AS-IV treatment apparently attenuated neurological dysfunction, reduced infarct volume and pathological damage, promoted the neurogenesis, and alleviated the pathological damage caused by cerebral I/R involved in thickening and blurring of synaptic membranes, reduction of microtubules and synaptic vesicles, and loss of synaptic cleft. Our study also showed that AS-IV promoted the transcription and expression of the peroxisome proliferators-activated receptors γ (PPARγ) and brain-derived neurotrophic factor (BDNF), increased the expression of phosphorylation of tyrosine kinase receptor B (TrkB) and downstream PI3K/Akt/mTOR pathway proteins. Notably, when GW9662, an inhibitor of PPARγ was administered with AS-IV, the neuroprotective effect of AS-IV was reduced. These findings suggested that AS-IV has neuroprotective function in CIRI rats, and its molecular mechanism may depend on the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signalling pathway activated by PPARγ. AS-IV could be an effective therapeutic drug candidate for CIRI treatment.

Combined Analysis of Human and Experimental Rat Samples Identified Biomarkers for Ischemic Stroke.

The genetic transcription profile and underlying molecular mechanisms of ischemic stroke (IS) remain elusive. To address this issue, four mRNA and one miRNA expression profile of rats with middle cerebral artery occlusion (MCAO) were acquired from the Gene Expression Omnibus (GEO) database. A total of 780 differentially expressed genes (DEGs) and 56 miRNAs (DEMs) were screened. Gene set and functional enrichment analysis revealed that a substantial number of immune-inflammation-related pathways were abnormally activated in IS. Through weighted gene co-expression network analysis, the turquoise module was identified as meaningful. By taking the intersection of the turquoise module genes, DEM-target genes, and all DEGs, 354 genes were subsequently obtained as key IS-related genes. Among them, six characteristic genes were identified using the least absolute shrinkage and selection operator. After validation with three external datasets, transforming growth factor beta 1 (Tgfb1) was selected as the hub gene. This finding was further confirmed by gene expression pattern analysis in both the MCAO model rats and clinical IS patients. Moreover, the expression of the hub genes exhibited a negative correlation with the modified Rankin scale score (P < 0.05). Collectively, these results expand our knowledge of the genetic profile and molecular mechanisms involved in IS and suggest that the Tgfb1 gene is a potential biomarker of this disease.