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Ischemic stroke induces a debilitating neurological insult, where inflammatory processes contribute greatly to the expansion and growth of the injury. Receptor-interacting protein kinase 2 (RIPK2) is most well-known for its role as the obligate kinase for NOD1/2 pattern recognition receptor signaling and is implicated in the pathology of various inflammatory conditions. Compared to a sham-operated control, ischemic stroke resulted in a dramatic increase in the active, phosphorylated form of RIPK2, indicating that RIPK2 may be implicated in the response to stroke injury. Here, we assessed the effects of pharmacological inhibition of RIPK2 to improve post-stroke outcomes in mice subjected to experimental ischemic stroke. We found that treatment at the onset of reperfusion with a RIPK2 inhibitor, which inhibits the phosphorylation and activation of RIPK2, resulted in marked improvements in post-stroke behavioral outcomes compared to the vehicle-administered group assessed 24 h after stroke. RIPK2 inhibitor-treated mice exhibited dramatic reductions in infarct volume, concurrent with reduced damage to the blood-brain barrier, as evidenced by reduced levels of active matrix metalloproteinase-9 (MMP-9) and leakage of blood-borne albumin in the ipsilateral cortex. To explore the protective mechanism of RIPK2 inhibition, we next pretreated mice with RIPK2 inhibitor or vehicle and examined transcriptomic alterations occurring in the ischemic brain 6 h after stroke. We observed a dramatic reduction in neuroinflammatory markers in the ipsilateral cortex of the inhibitor-treated group while also attaining a comprehensive view of the vast transcriptomic alterations occurring in the brain with inhibitor treatment through bulk RNA-sequencing of the injured cortex. Overall, we provide significant novel evidence that RIPK2 may represent a viable target for post-stroke pharmacotherapy and potentially other neuroinflammatory conditions., Competing Interests: Declaration of competing interest Dr. Shairaz Baksh is the president and CEO of BioImmuno Designs, Inc., and is affiliated with Bio-Stream Diagnostics, Inc. The rest of the authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke., Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome., Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]., Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Du, Jiang, Ren, Zhang, Kong and Li.)

Objective: c-myc has been reported to attenuate ischemia stroke (IS). We initiated the research to uncover the molecular mechanism of c-myc with regard to microRNA (miR)-200b-5p/Sirtuin1 (SIRT1) axis., Methods: An IS mouse model was prepared by middle cerebral artery occlusion (MCAO). Measurements of c-myc, miR-200b-5p and SIRT1 levels in MCAO mice were conducted. c-myc, miR-200b-5p and SIRT1 expression levels in MCAO mice were detected. The neurological function, production of inflammatory cytokines, neuronal apoptosis, brain tissue pathology and neuronal survival of MCAO mice were observed., Results: c-myc and SIRT1 levels went downward while miR-200b-5p expression went upward in MCAO mice. Elevation of c-myc or suppression of miR-200b-5p improved neurological function, reduced inflammation and neuronal apoptosis, and attenuated brain tissue pathology and neuronal survival of MCAO mice. Enhancement of miR-200b-5p or knockdown of SIRT1 weakened c-myc-induced protection against MCAO-induced brain injury in mice., Conclusion: Overall, c-myc protects mice from IS through elevating miR-200b-5p-targeted SIRT1 expression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Cell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke., Methods: Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation., Results: EPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, β-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, β-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10., Conclusion: These findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic stroke., (© 2020 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Specific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated., Methods: Retrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions., Results: Adjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions., Conclusion: A prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions. While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy. The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.

Background: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study's purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits. Methods: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods. Results: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier's analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions. Conclusions: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity. [ABSTRACT FROM AUTHOR]

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyGWC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and shortterm outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better. [ABSTRACT FROM AUTHOR]

ObjectivesTo research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke.MethodsData of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome.ResultsThe study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P

Background: Stroke is the major cause of mortality and permanent disability and is associated with an astonishing economic burden worldwide. In the past few decades, accumulated evidence has indicated that Xuesaitong (XST) has therapeutic benefits in cases of acute ischemic stroke (AIS). Our study aimed to provide the best current body of evidence of the efficacy and safety of XST for patients with AIS. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched eight electronic databases from inception to 17 July 2023 for relevant RCTs. The investigators independently screened trials, extracted data, and assessed the risk of bias. A meta-analysis was conducted using RevMan 5.3 and STATA 16.0 software. Results: In total, 46 RCTs involving 7,957 patients were included. The results showed that XST improved the long-term functional outcomes with lower modified Rankin Scale (mRS) scores (MD = -0.67; 95% CI [-0.92 to -0.42]; p < 0.00001) and a higher proportion of functional independence (mRS ≤2) (RR = 1.08; 95% CI [1.05 to 1.12]; p < 0.00001). Low-quality evidence indicated that XST improved the activities of daily living (MD = 10.17; 95% CI [7.28 to 13.06]; p < 0.00001), improved the neurological impairment (MD = -3.39; 95% CI [-3.94 to -2.84]; p < 0.00001), and enhanced the total efficiency rate (RR = 1.19; 95% CI [1.15 to 1.23]; p < 0.00001). No significant difference was found in the all-cause mortality or incidence of adverse events between the XST and control groups. The certainty of evidence was estimated as moderate to very low. Conclusion: Presently, the administration of XST within 14 days of AIS is associated with favorable long-term functional outcomes. In addition, XST can improve activities of daily living, alleviate neurological deficits, and has shown good tolerability. However, the current evidence is too weak, and the confidence of evidence synthesis was restricted by the high risk of bias. Given the insufficient evidence, appropriately sized and powered RCTs investigating the efficacy and safety of XST for patients with AIS are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of serum high-sensitivity C-reactive protein (hs-CRP) with the severity of neurological deficits and prognosis in patients with acute cerebral infarction (ACI). Patients and Methods: In this retrospective analysis, 119 patients with ACI were recruited from January to December 2020. The serum hs-CRP level was measured by a latex-enhanced immunoturbidimetric assay. The severity of neurological deficits and prognosis of ACI patients were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Multivariate logistic analysis was performed and receiver operating characteristic (ROC) curves were plotted to evaluate the value of hs-CRP in predicting the prognosis of ACI. Results: The patients with a more favorable prognosis (mRS score 0– 2) had a lower median serum hs-CRP level than those with a worse prognosis (mRS score 3– 6) (3.32 IQR: 1.51, 8.04 to 17.93 IQR:16.02, 19.01; P< 0.001). After adjusting for potential confounders, multivariable linear regression showed that serum hs-CRP level was independently associated with NIHSS score (Beta = 0.952, P< 0.001) and mRS score (Beta=0.878, P< 0.001). Multivariate logistic analysis revealed that high hs-CRP level was an independent predictor of the poor prognosis in patients with ACI (adjusted1 OR = 1.995; 95% CI = 1.499– 2.655; adjusted2 OR = 2.75; 95% CI = 1.015– 7.457). ROC curve analysis indicated that the area under the curve for hs-CRP to predict poor prognosis was 0.986. The cutoff value, sensitivity, and specificity were 11.835 mg/L, 95%, and 92.5%, respectively. In terms of ischemic stroke subtypes, the serum hs-CRP level was higher in large-artery atherosclerosis (LAA) patients than in those with small-artery occlusion (SAO) and cardioembolism (CE). In addition, the patients with LAA had higher scores of NIHSS and mRS than those with SAO and CE. Conclusion: Serum hs-CRP level is an independent predictor of prognosis, and an efficient index to discriminate patients with ACI, especially for those with LAA. [ABSTRACT FROM AUTHOR]

Infection is a major reason for poor stroke outcomes, and sepsis is a major cause of stroke-elated deaths. We herein examined whether NMDA receptor blockade, which was reported to exert anti-inflammatory actions, protects against the deleterious consequences of lipopolysaccharide (LPS)-induced sepsis-like state in adult male NMRI mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO). At 24 h post-ischemia, vehicle or Escherichia coli LPS (2 or 4 mg/kg) was intraperitoneally administered, whereas 30 min later vehicle or ketamine (10 mg/kg), which is a non-competitive NMDA receptor antagonist, was intraperitoneally applied. Delivery of LPS at a dosage of 4 mg/kg induced a sepsis-like state characterized by a rectal temperature reduction by ∼4.0°C, increased neurological deficits in Clark score, cylinder and open-field tests, increased brain infarct volume and reduced neuronal survival in the previously ischemic tissue. Notably, additional treatment with ketamine (10 mg/kg) significantly attenuated the sepsis-associated rectal temperature reduction by ∼1.5°C, reduced neurological deficits, reduced infarct volume, and promoted neuronal survival. Ketamine alone did not influence infarct volume or neurological deficits. Real-time PCR data analysis showed that GFAP , CD86 , CD206 , IL-1 β, and IL-10 mRNA levels were significantly increased in ischemic brains of LPS-treated compared with vehicle-treated mice. Additional treatment with ketamine significantly decreased IL-1 β and IL-10 , but not GFAP , CD86 , and CD206 mRNA levels. Our data show that ketamine at a dose that on its own does not confer neuroprotection reverses the adverse effects of LPS-induced sepsis-like state post-ischemia, presumably via immunomodulatory actions. [ABSTRACT FROM AUTHOR]

Infection is a major reason for poor stroke outcomes, and sepsis is a major cause of stroke-elated deaths. We herein examined whether NMDA receptor blockade, which was reported to exert anti-inflammatory actions, protects against the deleterious consequences of lipopolysaccharide (LPS)-induced sepsis-like state in adult male NMRI mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO). At 24 h post-ischemia, vehicle or Escherichia coli LPS (2 or 4 mg/kg) was intraperitoneally administered, whereas 30 min later vehicle or ketamine (10 mg/kg), which is a non-competitive NMDA receptor antagonist, was intraperitoneally applied. Delivery of LPS at a dosage of 4 mg/kg induced a sepsis-like state characterized by a rectal temperature reduction by ∼4.0°C, increased neurological deficits in Clark score, cylinder and open-field tests, increased brain infarct volume and reduced neuronal survival in the previously ischemic tissue. Notably, additional treatment with ketamine (10 mg/kg) significantly attenuated the sepsis-associated rectal temperature reduction by ∼1.5°C, reduced neurological deficits, reduced infarct volume, and promoted neuronal survival. Ketamine alone did not influence infarct volume or neurological deficits. Real-time PCR data analysis showed that GFAP, CD86, CD206, IL-1β, and IL-10 mRNA levels were significantly increased in ischemic brains of LPS-treated compared with vehicle-treated mice. Additional treatment with ketamine significantly decreased IL-1β and IL-10, but not GFAP, CD86, and CD206 mRNA levels. Our data show that ketamine at a dose that on its own does not confer neuroprotection reverses the adverse effects of LPS-induced sepsis-like state post-ischemia, presumably via immunomodulatory actions.

Abstract Background Specific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated. Methods Retrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions. Results Adjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015–1.048, P

Tuberculous meningitis (TBM) has a variety of clinical manifestations and complications, and ischemic stroke is a common complication of TBM. However, there is no established prevention or treatment for stroke associated with TBM, and the safety and efficiency of thrombolysis in acute stroke caused by TBM remain unknown. Herein, we present a case of successful intravenous thrombolysis in ischemic stroke caused by TBM. A 50-year-old male patient with cerebral infarction had substantially improved neurological function after intravenous thrombolysis, and he was subsequently found to have TBM. Our findings suggest that intravenous thrombolysis might be an effective acute treatment method for infectious stroke. [ABSTRACT FROM AUTHOR]

Sirtuin 3 (Sirt3) is a member of the Sirtuin family proteins and known to regulate multiple physiological processes such as metabolism and aging. As stroke is an aging-related disease, in this work, we attempt to examine the role and potential mechanism of Sirt3 in regulating ischemic stroke by using a permanent middle cerebral artery occlusion (pMCAO) model in wild type (WT) and Sirt3 knockout (KO) mice, coupled with oxygen glucose deprivation (OGD) experiments in cultured primary astrocytes. Sirt3 deficiency aggravated neuronal cell apoptosis and neurological deficits after brain ischemia. In addition, Sirt3 KO mice showed more severe blood–brain barrier (BBB) disruption and inflammatory responses compared with WT group in the acute phase. Furthermore, specific overexpression of Sirt3 in astrocytes by injecting glial fibrillary acidic protein (GFAP)::Sirt3 virus in ischemic region showed protective effect against stroke-induced damage. Mechanistically, Sirt3 could regulate vascular endothelial growth factor (VEGF) expression by inhibiting hypoxia inducible factor-1α (HIF-1α) signaling after ischemia (OGD). Our results have shown that Sirt3 plays a protective role in ischemic stroke via regulating HIF-1α/VEGF signaling in astrocytes, and reversal of the Sirt3 expression at the acute phase could be a worthy direction for stroke therapy. [ABSTRACT FROM AUTHOR]

Based on functional imaging methods of resting state DTI (Diffusion tensor imaging), this study reveals the structural changes and functional abnormalities of white matter fibers in patients with stroke from two levels of structure and function, and analyzes the effects of exercise on brain function remodeling in patients with stroke. The effects of the process, explore the central effect mechanism of scalp acupuncture to promote the recovery of motor function, and provide ideas for optimizing the rehabilitation treatment after stroke. There was no statistically significant difference in the general situation of the motion observation group and the conventional rehabilitation treatment group based on DTI technology at the time of enrollment, the NIHS S score, the fugl-meyerassessmenta score, the modified ashworth scale score, and the Brunnstrom staging assessment (P>0.05). After the week, 8 weeks, and 12 weeks of follow-up, the national institutes of health stroke scale, fugl-meyerassessmenta score, modified ashworth scale score, and Brunnstrom motor function staging score of the two groups of patients were significantly improved over time before treatment. The difference was statistically significant (P>0.05); the comparison between groups, the scores of patients in the action observation group and the difference before and after treatment were significantly higher than those in the conventional rehabilitation treatment group, and the difference was statistically significant (P>0.05). Conclusion: Action observation therapy can improve the degree of neurological deficits and promote the recovery of neurological function in patients with stroke. It can improve the score of motor function, reduce the muscle tension of key muscles in patients with stroke, and promote the recovery of motor function in patients.

Background: A cerebral ischemic stroke involves mitochondrial dysfunction, motor deficits, and paralysis; and Danhong injection (DHI) might possess mitochondrial protection and functional recovery in a stroke subject through promoting expression of parkin, a ubiquitin ligase playing a key role in the regulation of proteins and mitochondria quality control. Objective: To investigate the therapeutic effects of DHI on the histological, cellular, and functional recovery of Wistar rats after middle cerebral artery occlusion/reperfusion (MCAO/R). Methods: One hundred and twenty healthy male Wistar rats (250–300 g), were randomly assigned to six groups (twenty rats/group). Rats were subjected to 1 h MCAO/R and subsequently administered the intravenous doses of DHI (0.75, 1.5, and 3 mL/kg) to the respective groups (twice a day for 14 days). Unlike the other groups, the sham group received surgery without vessel occlusion. All the animals were tested for gait behavior using the CatWalk system. The body weight/survival rates were recorded daily for 14 days. The parkin protein expression of the brain tissue was quantified by immunohistochemistry analysis. Additionally, cultured cortical neurons were incubation with DHI or minocycline (MC) and then deprived of oxygen and glucose for 2 h (to resemble ischemic/reperfusion), followed by 4 h reoxygenation. Cellular and mitochondrial phenotypes were assayed by high content analysis. Results: Neurological integrity and paw parameters of the animals were altered in the model group but significantly ameliorated by DHI administration. Also, the infarct volume and survival rate were significantly improved in DHI groups. DHI enhanced the expression of parkin protein in the brain and improved the relative mitochondrial reductase activity of the cultured neurons. Conclusions: The overall result shows that daily intervention with DHI provides neuroprotection and survival to improve gait motion in Wistar rats. [ABSTRACT FROM AUTHOR]

Increased oxidative stress and free radicals can cause neuron cell damage. Serum 8-hydroxy-2-deoxyguanosine (8-OHdG) concentration is the result of free radical interactions with cluster C8 guanine bases, which is used to assess the degree of neuron cells damage and the oxidative stress levels. Increased serum 8-OHdG concentration indicating brain cells damage is reflected in neurological deficits based on the The National Institutes of Health Stroke Scale (NIHSS). The aim of this study was to determine the correlation between serum 8-OHdG concentration and the degree of neurological deficit by NIHSS. This was an observational cross-sectional study. Seventy-two patients with acute ischemic stroke who visited Dr. Hasan Sadikin General Hospital Bandung during the period of August 2013 to January 2014 were enrolled. Statistical analysis was performed using Kruskal-Wallis test and rank Spearman’s correlation test. The mild neurological deficit median serum 8-OHdG concentrations was 3.9 ng/mL (3.3–12.0 ng/mL), moderate was 23 ng/mL (8.0–51.0 ng/mL), and severe was 77.5 ng/mL (54.0–97.0 ng/mL). Correlation of serum 8-OHdG concentration with neurological deficits in acute ischemic stroke rs=0.912 (p

Background: Hyperbaric oxygenation (HBO2) involves breathing 100% oxygen under elevated ambient pressure in a hyperbaric chamber, thereby dissolving oxygen in the plasma. This results in an increase of arterial partial pressure of oxygen (pO2). Though well established in experimental studies, HBO2 treatment for ischemic stroke is still under discussion. Methods: From 2002-2014 HBO2 (2.2 bar, 90 minutes one/day; average number per patient: 4.7) was applied in 49 consecutive patients (32 males, 17 females, mean age: 68.8 years, range 31.2 - 83.9) with acute neurological deficit following cardiac surgery (CABG 15; combined surgery 14; valve surgery 11;, aneurysm repair 8; malformation 1). Patients' history including TIA or stroke and carotid artery pathology were documented. Both degree and type of neurological deficit was evaluated by a scoring system (0-4) before and after HBO2 treatment. Results: Before HBO2 therapy, the average motor deficit score was 2.45 and the average speech disorder score was 0.55, as compared with an average motor deficit of 1.12 and an average speech disorder of 0.27 afterward (α=0.0001, α=0.009). The majority of patients had an overall improvement of 2 score-points after HBO2 therapy (n=23 patients). Probit analysis showed that for a 50% response/probability (LC50) of having an overall outcome of ≥2 scoring points, an estimate of 4.3 HBO2 therapy sessions is necessary. Conclusion: HBO2 therapy was associated with significant improvement in patients with acute neurological deficits due to ischemic stroke following cardiac surgery. Though this fact suggests gas embolism as the most likely cause of stroke in this collective, other underlying pathologies cannot be ruled out. Randomized studies are needed for further evaluation. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that angiogenesis, through new blood vessel formation, results in improved collateral circulation and may impact the long-term recovery of patients. In this study, we first investigated the preventive action of a 5-week pretreatment of MLC901, an herbal extract preparation derived from Chinese medicine, against the deleterious effects of ischemic stroke and its effects on angiogenesis in a model of focal ischemia in mice. Methods: The stroke model was induced by 60 min of middle cerebral artery occlusion followed by reperfusion. MLC901 was administered in the drinking water of animals (6 g/l) for 5 weeks before ischemia and then during reperfusion. Results: MLC901 treatment increased the survival rate, reduced the cerebral infarct area and attenuated the blood brain barrier leakage as well as the neurologic dysfunction following ischemia and reperfusion. We provide evidence that MLC901 enhances endothelial cell proliferation and angiogenesis by increasing the number of neocortical vessels in the infarcted area. MLC901 regulates the expression of hypoxic inducible factor 1a and its downstream targets such as vascular endothelial growth factor and angiopoietins 1 and 2. This work also shows that erythropoietin is an important player in the enhancement of angiogenesis by MLC901. Conclusions: These results demonstrate therapeutic properties of MLC901, in addition to those previously described, in stimulating revascularization, neuroprotection and repair of the neurovascular unit after ischemic stroke. [ABSTRACT FROM AUTHOR]

The poor quality of life after a stroke is largely attributed to deficits in cognitive-motor functioning. The goals of this study were to detect if damaged motor learning function were attributed to motor deficits in rats following a transient middle cerebral artery (MCA) occlusion. Stroke was induced by a 2-h occlusion of the MCA using an intraluminal filament. Motor functions were evaluated from 5 up to 28 days after reperfusion in ischemic and control rats. Motor function was detected by a series of motor tests (runway traversing and beam balancing, as well as foot fault placing, parallel bar crossing, rope and ladder climbing), and motor learning behavior was determined by analyzing the rate of improvement of impaired function during performance of the motor tasks. Significant (P<0.001) motor deficits were detected in the stroke group (n=10) while performing motor tasks that involve extensive coordination, in comparison to the controls (n=12). Although motor behavior was improved with repeated behavior testing, unparalleled rate of improvement of motor performance on rope and ladder climbing tests was found between the two groups, suggesting an impaired motor learning function. Brain tissue damage was detected in the ischemic animals 28 days after surgery, demonstrated by 40% infarct volume of contralateral hemisphere. Both motor learning and motor function were impaired in ischemic rats. The motor tests used in this study are sensitive, semi-quantitative, and reproducible measurements of functional impairment in rats following an ischemic stroke. [Copyright &y& Elsevier]

The neuroprotective effects of isradipine, a 2,4-dihydropyridine calcium channel blocker, has been well studied in the rat model of focal ischemia (induced by middle cerebral artery occlusion, MCAO). The present study was designed to evaluate whether isradipine pretreatment caused early (0–3 h after stroke) ischemic changes in diffusion- weighted magnetic resonance imaging (DWI) and if such changes were predictive of previously documented protection in brain infarction. An initial dose-response study using neurological deficit scores and estimates of protection from brain infarction (by histology) showed that isradipine reduced cortical infarctions compared to vehicle-treated animals at most doses (between 1.25 and 5 mg/kg/day s.c. for 6 days) with the best results obtained at 5 mg/kg/day, where a 78.5% reduction was observed. This dose was utilized to perform the DWI study. Early quantitative estimates of infarct size, as measured by DWI at 1, 2 and 3 h after MCAO, were similar to those obtained with late histology at 24 h. These data indicate that in pretreatment protocols, DWI can be used to quantitatively predict areas at risk of permanent damage. This work also demonstrates that neurological deficits, developing from the damaged forebrain following focal stroke, may provide an index of isradipine’s neuroprotective activity. [ABSTRACT FROM AUTHOR]