[Mechanism of astragaloside â £ combined with Panax notoginseng saponins in regulating angiogenesis to treat cerebral ischemia based on network pharmacology and experimental verification].

Network pharmacology and animal and cell experiments were employed to explore the mechanism of astragaloside Ⅳ(AST Ⅳ) combined with Panax notoginseng saponins(PNS) in regulating angiogenesis to treat cerebral ischemia. The method of network pharmacology was used to predict the possible mechanisms of AST Ⅳ and PNS in treating cerebral ischemia by mediating angiogenesis. In vivo experiment: SD rats were randomized into sham, model, and AST Ⅳ(10 mg·kg~(-1)) + PNS(25 mg·kg~(-1)) groups, and the model of cerebral ischemia was established with middle cerebral artery occlusion(MCAO) method. AST Ⅳ and PNS were administered by gavage twice a day. the Longa method was employed to measure the neurological deficits. The brain tissue was stained with hematoxylin-eosin(HE) to reveal the pathological damage. Immunohistochemical assay was employed to measure the expression of von Willebrand factor(vWF), and immunofluorescence assay to measure the expression of vascular endothelial growth factor A(VEGFA). Western blot was employed to determine the protein levels of vascular endothelial growth factor receptor 2(VEGFR2), VEGFA, phosphorylated phosphatidylinositol 3-kinase(p-PI3K), and phosphorylated protein kinase B(p-AKT) in the brain tissue. In vitro experiment: the primary generation of rat brain microvascular endothelial cells(rBEMCs) was cultured and identified. The third-generation rBMECs were assigned into control, model, AST Ⅳ(50 µmol·L~(-1)) + PNS(30 µmol·L~(-1)), LY294002(PI3K/AKT signaling pathway inhibitor), 740Y-P(PI3K/AKT signaling pathway agonist), AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P groups. Oxygen glucose deprivation/re-oxygenation(OGD/R) was employed to establish the cell model of cerebral ischemia-reperfusion injury. The cell counting kit-8(CCK-8) and scratch assay were employed to examine the survival and migration of rBEMCs, respectively. Matrigel was used to evaluate the tube formation from rBEMCs. The Transwell assay was employed to examine endothelial cell permeability. Western blot was employed to determine the expression of VEGFR2, VEGFA, p-PI3K, and p-AKT in rBEMCs. The results of network pharmacology analysis showed that AST Ⅳ and PNS regulated 21 targets including VEGFA and AKT1 of angiogenesis in cerebral infarction. Most of these 21 targets were involved in the PI3K/AKT signaling pathway. The in vivo experiments showed that compared with the model group, AST Ⅳ + PNS reduced the neurological deficit score(P<0.05) and the cell damage rate in the brain tissue(P<0.05), promoted the expression of vWF and VEGFA(P<0.01) and angiogenesis, and up-regulated the expression of proteins in the PI3K/AKT pathway(P<0.05, P<0.01). The in vitro experiments showed that compared with the model group, the AST Ⅳ + PNS, 740Y-P, AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P improved the survival of rBEMCs after OGD/R, enhanced the migration of rBEMCs, increased the tubes formed by rBEMCs, up-regulated the expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.05, P<0.01). Compared with the LY294002 group, the AST Ⅳ + PNS + LY294002 group showed increased survival rate, migration rate, and number of tubes, up-regulated expression of proteins in the PI3K/AKT pathway, and decreased endothelial cell permeability(P<0.05,P<0.01). Compared with the AST Ⅳ + PNS and 740Y-P groups, the AST Ⅳ + PNS + 740Y-P group presented increased survival rate, migration rate, and number of tubes and up-regulated expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.01). This study indicates that AST Ⅳ and PNS can promote angiogenesis after cerebral ischemia by activating the PI3K/AKT signaling pathway.

Rare instances of concomitant acute myocardial infarction and stroke.

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.

Chemical angioplasty vs. balloon plus chemical angioplasty for delayed cerebral ischemia: a pilot study of PbtO2 outcomes.

BACKGROUND: Delayed cerebral ischaemia (DCI) is a major cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Chemical angioplasty (CA) and transluminal balloon angioplasty (TBA) are used to treat patients with refractory vasospasm causing DCI. Multi-modal monitoring including brain tissue oxygenation (PbtO2) is routinely used at this centre for early detection and management of DCI following aSAH. In this single-centre pilot study, we are comparing these two treatment modalities and their effects on PbtO2. METHODS: Retrospective case series of patients with DCI who had PbtO2 monitoring as part of their multimodality monitoring and underwent either CA or TBA combined with CA. PbtO2 values were recorded from intra-parenchymal Raumedic NEUROVENT-PTO® probes. Data were continuously collected and downloaded as second-by-second data. Comparisons were made between pre-angioplasty PbtO2 and post-angioplasty PbtO2 median values (4 h before angioplasty, 4 h after and 12 h after). RESULTS: There were immediate significant improvements in PbtO2 at the start of intervention in both groups. PbtO2 then increased by 13 mmHg in the CA group and 15 mmHg in the TBA plus CA group in the first 4 h post-intervention. This improvement in PbtO2 was sustained for the TBA plus CA group but not the CA group. CONCLUSION: Combined balloon plus chemical angioplasty results in more sustained improvement in brain tissue oxygenation compared with chemical angioplasty alone. Our findings suggest that PbtO2 is a useful tool for monitoring the response to angioplasty in vasospasm.

The Relationship Between Composite Inflammatory Ratios and Complications of Massive Ischaemic Stroke.

OBJECTIVE: To investigate the relationship between complications of massive cerebral infarction (MCI) and composite inflammatory ratios. STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Neurology, Affiliated Hospital of Putian University, Putian, China, from January 2019 to November 2021. METHODOLOGY: Eighty-two patients with MCI underwent blood tests within 24 hours of admission. Complications such as cerebral herniation, haemorrhage transformation (HT), and stroke-associated pneumonia (SAP) were evaluated based on imaging examinations. The prognosis was assessed using the modified Rankin Scale score (mRS) at discharge. RESULTS: Among the 82 patients, the cerebral herniation group had higher levels of systemic immune inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) compared to the non-cerebral herniation group. MCI patients who developed HT had higher levels of SII, NLR, mean platelet volume/platelet (MPV/PLT), and platelet-to-lymphocyte ratio (PLR). The SAP group had higher levels of MPV/PLT and NLR compared to the non-SAP group. The poor prognosis group had higher SII and NLR levels but a lower lymphocyte-to-monocyte ratio (LMR) compared to the good prognosis group. CONCLUSION: NLR showed high accuracy in predicting complications and the short-term prognosis of MCI. SII was linked to cerebral herniation, HT, and the short-term prognosis of MCI. MPV/PLT was found to be related to SAP and HT caused by MCI. LMR may act as a protective factor for the short-term prognosis of MCI. KEY WORDS: Massive cerebral infarction, Neutrophil-to-lymphocyte ratio, Systemic immune inflammation index, Prognosis.

Case report: unprecedented case of infantile cerebral infarction following COVID-19 and favorable outcome.

The 2019 novel coronavirus, SARS-CoV-2, was highly prevalent in China as of December 2022, causing a range of symptoms, predominantly affecting the respiratory tract. While SARS-CoV-2 infection in children is generally mild, severe cases, especially in infants, are rare. We present a case of a previously healthy 7-month-old infant who developed cerebral infarction and coagulation dysfunction three days after COVID-19 onset. Clinically, the infant had weakness in the left limbs and pinpoint bleeding spots. A cranial magnetic resonance imaging showed ischemic strokes in the right basal ganglia and thalamus. Laboratory tests indicated thrombocytopenia and coagulation dysfunction. Inflammatory cytokines like interleukin-10 were elevated, with increased CD3+, CD4+, and CD8+ T lymphocytes but decreased CD3- CD16+ CD56+ natural killer cells. Treatment included mannitol, dexamethasone, oral aspirin, and vitamins B1 and B6 for reducing intracranial pressure, antiinflammation, anticoagulation, and nerve support, respectively. During the recovery phase, rehabilitation therapy focused on strength training, fine motor skills, and massage therapy. The infant gradually improved and successfully recovered. While rare, such cases can lead to severe complications. These combined efforts were instrumental in achieving significant functional recovery in the patient, demonstrating that even in severe instances of pediatric cerebral infarction due to COVID-19, positive outcomes are attainable with early and comprehensive medical response.

Wasp sting-induced bilateral thalamic and midbrain infarction.

A male patient in his early 40s presented to the emergency department with an acute onset of respiratory distress and facial oedema, indicative of anaphylaxis. These symptoms emerged 2 hours subsequent to a wasp sting on the left side of his face. Despite initial stabilisation, the patient's state deteriorated into somnolence and disorientation. Notably, he denied any history of seizures, sensory or motor deficits, or bowel/bladder complications. Physical examination unveiled no focal neurological deficits. Routine laboratory tests and drug screening yielded no significant findings. Subsequent brain MRI with angiography exposed bilateral thalami diffusion restriction, strongly implying an acute infarction within the artery of Percheron territory, an atypical vascular variant. The sequence of events, alongside the absence of other conclusive aetiologies, indicated a wasp sting-induced thalamic infarction driven by vasogenic and thrombogenic effects of inflammatory substances.

Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

Bibliometric analysis: Hot spots and frontiers in acupuncture treatment of cerebral infarction.

OBJECTIVE: CiteSpace6.1.R2 is used to analyze the research status of acupuncture in the treatment of cerebral infarction, and to find relevant hot spots and frontiers. METHODS: The researchers searched the Web of Science Core Collection database. The search date is from the establishment of the database to August 31, 2023. The search terms and expressions are: ("Cerebral Infarction" OR "Ischemic stroke") AND ("Acupuncture" OR "fire needle"). The researchers used CiteSpace software to draw a knowledge map to explore the hot spots and frontiers of acupuncture in treating cerebral infarction. RESULTS: We screened 414 articles in the Web of Science Core Collection database. China is the country with the largest number of publications, with a total of 343 papers published. China's institutions cooperate most closely, and cooperation between countries is less and more scattered. The author with the highest number of published articles is Chen L, with a total of 31 published articles. The research focus mainly revolves around the mechanism of acupuncture treatment of cerebral infarction and electroacupuncture treatment of cerebral infarction. Among them, acupuncture treatment of cerebral infarction is the most. CONCLUSION: According to CiteSpace's analysis results, China is at the forefront of this research field, while other countries have less research in this field and little cooperation among countries. At present, the mainstream aspect of research is the mechanism of acupuncture treatment of cerebral infarction electroacupuncture and acupuncture points. Therefore, in future research, we should pay more attention to the treatment of cerebral infarction mechanism of acupuncture, problems with the type of acupuncture used, and acupuncture points.

Asprosin improved neuronal survival by suppressing apoptosis and enhancing the activity of the autophagy pathway in the MCAO model in rats.

OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model. MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis' test was used to compare differences between groups. p<0.05 was considered statistically significant. RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05). CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more.

Moxibustion preconditioning reduces inflammatory response in rats with cerebral ischemia-reperfusion injury by regulating PI3K / AKT / mTOR signaling pathway. / 艾灸预处理通过调控PI3K/AKT/mTORä¿¡å·é€šè·¯å‡è½»è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç‚Žæ€§ååº”.

OBJECTIVES: To observe the effect of moxibustion preconditioning on inflammatory response in rats with cerebral ischemia reperfusion injury (CIRI), so as to explore its mechanisms underlying improving CIRI. METHODS: Seventy-five male SD rats were randomly divided into sham operation, model, moxibustion preconditioning 3 days (Moxi 1), moxibustion preconditioning 5 days (Moxi 2) and moxibustion preconditioning 7 days (Moxi 3) groups, with 15 rats in each group. Moxibustion was applied at "Baihui"(GV20), "Dazhui"(GV14) and "Zusanli"(ST36) for 20 min once a day, totally for 3, 5 or 7 days. Thirty minutes after the last moxibustion treatment, the CIRI model was established by occlusion of the middle cerebral artery. The neurological deficit score was assessed by using Longa's method. The infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The morphological changes of cortical neurons were observed by HE staining. The contents of inflammatory factors interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S-100ß protein (S-100ß) and neuron-specific enolase (NSE) were detected by ELISA. The expression of phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and mammalian target of rapamycin (mTOR) proteins in the ischemic cortex tissues were detected by immunohistochemistry and Western blot. RESULTS: Compared with the sham operation group, the neurological function score and the percentage of cerebral ischemic volume were increased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly increased (P<0.01), while the protein expressions of PI3K, p-PI3K, AKT and mTOR in the cerebral cortex were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function score and the percentage of cerebral ischemic volume were significantly decreased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly decreased (P<0.01), and the expressions of PI3K, p-PI3K, AKT and mTOR proteins in the cerebral cortex were significantly increased (P<0.01) in three moxibustion groups. Compared with the Moxi 1 and Moxi 2 groups, the above indicators were significantly improved in rats of the Moxi 3 group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion preconditioning can significantly improve the neurological function of rats after ischemia-reperfusion, inhibit serum inflammatory factors IL-1 ß and TNF-α, inhibit brain tissue injury markers S-100ß and NSE, which may be related to the activation of PI3K/AKT/mTOR signaling pathway. The protective effect of moxibustion preconditioning for 7 days on CIRI was better than that of 5 days and 3 days.

Progress of researches on mechanisms of acupuncture underlying improvement of cerebral ischemia-reperfusion injury by regulating calcium overload. / é’ˆåˆºè°ƒæŽ§è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤åŽé’™è¶ è½½æœºåˆ¶ç ”ç©¶è¿›å±•.

Ischemic stroke is currently the most common type of stroke, and the key pathological link is cerebral ischemia-reperfusion injury (CIRI), while the key factor leading to apoptosis and necrosis of ischemic nerve cells is calcium overload. Current studies have confirmed that acupuncture therapy has a good modulating effect on calcium homeostasis and can reduce cerebral ischemia-reperfusion induced damage of neuronal cells by inhibiting calcium overload. After reviewing the relevant literature published in the past 15 years, we find that acupuncture plays a role in regulating the pathological mechanism of calcium overload after CIRI by inhibiting the opening of connexin 43 hemichannels, regulating the intracellular free calcium ion concentration, suppressing the expression of calmodulin, and blocking the function of L-type voltage-gated calcium channels, thereby inhibiting calcium overload, regulating calcium homeostasis and antagonizing neuronal damage resulted from cerebral ischemia-reperfusion, which may provide ideas for future research.

[Imaging of In Vivo Oxygen Tension Based on Phosphorescence Lifetime Microscopy].

Molecular oxygen plays essential roles in aerobic organisms as a terminal electron acceptor in the electron transport chain in mitochondria. The intracellular oxygen concentration of the entire body is strictly regulated by a balance between the supply of oxygen from blood vessels and the consumption of oxygen in mitochondria. The disruption of oxygen homeostasis in the body often results in serious pathologies such as cancer, cerebral infarction, and chronic kidney disease, and thus considerable effort has been devoted to the development of suitable techniques allowing the qualitative and quantitative detection of tissue oxygen levels. This review focuses on recent advances in the visualization of oxygen levels in tissue based on phosphorescence lifetime measurements using exogenously small molecular oxygen probes. Specially, I introduce the principle of oxygen sensing by means of phosphorescence quenching, recent advances in intracellular and intravascular oxygen probes based on iridium(III) complexes, a system for measuring phosphorescence lifetime combined with confocal scanning microscopy, and the applications of these technologies to in vivo oxygen measurements, emphasizing the usefulness of iridium(III) complexes as biological oxygen probes.

[Efficacy of Mexidol in combination with cerebral revascularization in the treatment of ischemic stroke]. / Effektivnost' primeneniya Meksidola v kombinatsii s revaskulyarizatsiei golovnogo mozga v terapii ishemicheskogo insul'ta.

Stroke is an acute life-threatening condition; its outcome is determined by the degree of damage to brain tissue, the quality and speed of medical care in the first minutes and hours after its occurrence. The main mechanism of brain tissue damage during both ischemia and reperfusion is oxidative stress. The review covers adverse influence oxidative stress at the cerebral ischemia and reperfusion periodes of ischemic stroke. The results of preclinical studies demonstrating the ability of Mexidol to neutralize the effects of free radicals and activate antioxidant protection are presented. Data from clinical studies of the use of Mexidol in combination with thrombolysis in patients with ischemic stroke are reviewed.

Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy.

OBJECTIVE: To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury (CIRI) and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4 (NCOA4) mediated ferritinophagy. METHODS: Sprague-Dawley male rats were divided into four groups: the sham group, model group, acupuncture group, and sham acupuncture group. After 2 h of middle cerebral artery occlusion (MCAO), reperfusion was performed for 24 h to induce CIRI. The rats were treated with acupuncture at the Neiguan (PC6) and Shuigou (GV26) acupoints. Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion. Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion. The malondialdehyde (MDA) and ferrous iron (Fe2+) levels were observed after 24 h of reperfusion using an assay kit. Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1 (FTH1) at 24 h after reperfusion. Moreover, the colocalization of ferritin with neurons, NCOA4 with microtubule-associated protein 1 light chain 3 (LC3), and NCOA4 with ferritin was visualized using immunofluorescence staining. RESULTS: Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group. Following CIRI, the expression of NCOA4, LC3 and FTH1 was increased, which enhanced ferritinophagy and induced an inappropriate accumulation of Fe2+ and MDA in the ischaemic brain. However, acupuncture dramatically downregulated the expression of NCOA4, LC3 and FTH1, inhibited the overactivation of ferritinophagy, and decreased the levels of MDA and Fe2+. CONCLUSIONS: Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.

Intravenous Thrombolysis Before Thrombectomy Improves Functional Outcome After Stroke Independent of Reperfusion Grade.

BACKGROUND: We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large-vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration. METHODS AND RESULTS: We included consecutive patients with anterior circulation large-vessel occlusion from our prospective registry of thrombectomy-eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy-eligible patients (513 women; median age, 77 years [interquartile range, 67-84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0-2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32-0.75]; P=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31-0.74]; P=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35-point decrease in 90-day modified Rankin Scale score (ß=-0.35 [95 CI%, -0.68 to 0.01]; P=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=-1.79 [95% CI, -3.43 to -0.15]; P=0.03) and distal thrombus migration (ß=-0.41 [95% CI, -0.69 to -0.13]; P=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=-0.46 [95% CI, -0.74 to -0.17]; P=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=-0.47 [95% CI, -0.96 to 0.01]; P=0.05). CONCLUSIONS: In thrombectomy-eligible patients with anterior circulation large-vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.

TIGAR reduces neuronal ferroptosis by inhibiting succinate dehydrogenase activity in cerebral ischemia.

Ischemia Stroke (IS) is an acute neurological condition with high morbidity, disability, and mortality due to a severe reduction in local cerebral blood flow to the brain and blockage of oxygen and glucose supply. Oxidative stress induced by IS predisposes neurons to ferroptosis. TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits the intracellular glycolytic pathway to increase pentose phosphate pathway (PPP) flux, promotes NADPH production and thus generates reduced glutathione (GSH) to scavenge reactive oxygen species (ROS), and thus shows strong antioxidant effects to ameliorate cerebral ischemia/reperfusion injury. However, in the current study, prolonged ischemia impaired the PPP, and TIGAR was unable to produce NADPH but was still able to reduce neuronal ferroptosis and attenuate ischemic brain injury. Ferroptosis is a form of cell death caused by free radical-driven lipid peroxidation, and the vast majority of ROS leading to oxidative stress are generated by mitochondrial succinate dehydrogenase (SDH) driving reverse electron transfer (RET) via the mitochondrial electron transport chain. Overexpression of TIGAR significantly inhibited hypoxia-induced enhancement of SDH activity, and TIGAR deficiency further enhanced SDH activity. We also found that the inhibitory effect of TIGAR on SDH activity was related to its mitochondrial translocation under hypoxic conditions. TIGAR may inhibit SDH activity by mediating post-translational modifications (acetylation and succinylation) of SDH A through interaction with SDH A. SDH activity inhibition reduces neuronal ferroptosis by decreasing ROS production, eliminating MitoROS levels and attenuating lipid peroxide accumulation. Notably, TIGAR-mediated inhibition of SDH activity and ferroptosis was not dependent on the PPP-NADPH-GPX4 pathways. In conclusion, mitochondrial translocation of TIGAR in prolonged ischemia is an important pathway to reduce neuronal ferroptosis and provide sustainable antioxidant defense for the brain under prolonged ischemia, further complementing the mechanism of TIGAR resistance to oxidative stress induced by IS.

Impact of increased trunk muscle mass on trunk function and activities of daily living in older individuals with cerebral infarction.

BACKGROUND & AIMS: The association between trunk muscle mass or trunk function or trunk muscle strength and activities of daily living (ADLs) has been reported, but no studies have examined the impact of increased trunk muscle mass on trunk function or ADL. This study aimed to determine whether increased trunk muscle mass is associated with trunk function and ADL in older individuals with cerebral infarction during rehabilitation. METHODS: This retrospective observational study enrolled 158 patients with cerebral infarction aged ≥65 years who were admitted for post-stroke rehabilitation. The trunk muscle mass index (TMI) was calculated at admission and discharge using bioelectrical impedance analysis. Patients were divided into two groups: one with increased TMI (64 participants; 41 %) and the other without TMI increase (94 participants; 59 %). Multiple linear regression analysis was performed with functional assessment for control of trunk (FACT) or functional independence measure (FIM)-motor gain as the objective variable and increased TMI group as the explanatory variable. RESULTS: We analyzed a total of 158 patients (79.5 ± 7.8 years of age, 51.9 % men). TMI increase was independently associated with FACT gain (coefficient = 1.413, 95 % confidence interval = 0.34-2.49, P = 0.010), but not with FIM-motor gain. CONCLUSIONS: The results suggest that increased TMI is independently associated with recovery of trunk function. Further prospective studies are needed to elucidate the relationship between increased TMI and ADL.

Predictive model for the risk of hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: To systematically review the risk prediction model of Hemorrhages Transformation (HT) after intravenous thrombolysis in patients with Acute Ischemic Stroke (AIS). METHODS: Web of Science, The Cochrane Library, PubMed, Embase, CINAHL, CNKI, CBM, WanFang, and VIP were searched from inception to February 25, 2023 for literature related to the risk prediction model for HT after thrombolysis in AIS. RESULTS: A total of 17 included studies contained 26 prediction models, and the AUC of all models at the time of modeling ranged from 0.662 to 0.9854, 16 models had AUC>0.8, indicating that the models had good predictive performance. However, most of the included studies were at risk of bias. the results of the Meta-analysis showed that atrial fibrillation (OR=2.72, 95% CI:1.98-3.73), NIHSS score (OR=1.09, 95% CI:1.07-1.11), glucose (OR=1.12, 95% CI:1.06-1.18), moderate to severe leukoaraiosis (OR=3.47, 95% CI:1.61-7.52), hyperdense middle cerebral artery sign (OR=2.35, 95% CI:1.10-4.98), large cerebral infarction (OR=7.57, 95% CI:2.09-27.43), and early signs of infarction (OR=4.80, 95% CI:1.74-13.25) were effective predictors of HT after intravenous thrombolysis in patients with AIS. CONCLUSIONS: The performance of the models for HT after thrombolysis in patients with AIS in the Chinese population is good, but there is some risk of bias. Future post-intravenous HT conversion prediction models for AIS patients in the Chinese population should focus on predictors such as atrial fibrillation, NIHSS score, glucose, moderate to severe leukoaraiosis, hyperdense middle cerebral artery sign, massive cerebral infarction, and early signs of infarction.