<![CDATA[Current Neurovascular Research (Volume 20 - Issue 4)]]> https://eurekaselect.com/journal/31 RSS Feed for Journals | BenthamScience EurekaSelect (+https://eurekaselect.com) 2023-12-29 <![CDATA[Current Neurovascular Research (Volume 20 - Issue 4)]]> https://eurekaselect.com/journal/31 <![CDATA[Clinical Depression, the Mechanistic Target of Rapamycin (mTOR), and Forkhead Transcription Factors (FoxOs)]]>https://eurekaselect.com/article/1347042023-12-29 <![CDATA[Intravenous Thrombolysis is Effective in Mild Stroke Patients with an Admission NIHSS Score of 3 to 5]]>https://eurekaselect.com/article/1357672023-12-29 Background and Purpose: The role of intravenous thrombolysis in patients with acute mild ischemic stroke remains highly controversial. Therefore, this study aims to analyze the efficacy and safety of intravenous thrombolysis in patients with mild ischemic stroke based on admission National Institutes of Health Stroke Scale (NIHSS) score.

Methods: The present study enrolled 507 patients with acute mild ischemic stroke admitted within 4.5 hours of symptom onset with an admission NIHSS score of 0 to 5. Patients were assigned to two groups based on admission NIHSS scores of 0 to 2 and 3 to 5, and subsequent analyses compared functional outcomes between thrombotic and non-thrombotic patients within these groups. The primary outcome was a modified Rankin score (mRS) of 0 or 1 at 90 days, representing functional independence. The safety outcomes were symptomatic intracranial hemorrhage (sICH), early neurological deterioration (END), and the rate of stroke recurrence within 90 days.

Results: Among the 267 patients with NIHSS scores of 0 to 2, 112 (41.9%) patients received intravenous thrombolysis. Overall, thrombolysis administration did not significantly improve the patient's functional prognoses at 90 days (adjusted OR=1.046, 95%CI=0.587-1.863, p = 0.878). However, there was a marked increase in the risk of sICH (p = 0.030). Of the 240 patients with NIHSS scores of 3 to 5, 155 (64.6%) patients received intravenous thrombolysis, resulting in a significant improvement in 90-day functional prognosis (adjusted OR=3.284, 95%CI=1.876- 5.749, p < 0.001) compared to those that did not receive thrombolysis intervention. Importantly, there was no significant increase in sICH incidence (adjusted OR=2.770, 95%CI=0.313-24.51, p = 0.360). There were no statistically significant differences in END or the rate of stroke recurrence within 90 days between thrombotic and non-thrombotic groups.

Conclusions: Intravenous thrombolysis is safe and effective in patients with baseline NIHSS scores of 3 to 5. In contrast, it did not improve 90-day functional outcomes in patients with NIHSS scores of 0 to 2 and instead increased the risk of sICH.

]]> <![CDATA[Smurf2-Mediated Ubiquitination of FOXO4 Regulates Oxygen-glucose Deprivation/Reperfusion-induced Pyroptosis of Cortical Neurons]]>https://eurekaselect.com/article/1351782023-12-29 Background: Smad ubiquitination regulatory factor 2 (Smurf2) has been observed to alleviate ischemia-reperfusion injury. This study sought to explore the molecular mechanism of Smurf2-mediated forkhead box O4 (FOXO4) ubiquitination in oxygen-glucose deprivation/ reperfusion (OGD/R)-induced pyroptosis of cortical neurons.

Methods: Human cortical neurons (HCN-2) were subjected to OGD/R to establish a cell model of cerebral stroke. Smurf2, FOXO4, and doublecortin domain containing 2 (DCDC2) expressions were determined by RT-qPCR and Western blot. LDH release, pyroptosis-related proteins NLRP3, GSDMD-N, and cleaved-caspase-3, as well as inflammatory factors IL-1β and IL-18, were assessed by LDH assay kit, Western blot, and ELISA. The ubiquitination level of FOXO4 was determined by ubiquitination assay. The bindings of Smurf2 to FOXO4 and FOXO4 to DCDC2 were testified by Co-IP, ChIP, and dual-luciferase assays. Rescue experiments were designed to validate the role of FOXO4/DCDC2 in the pyroptosis of HCN-2 cells.

Results: Smurf2 was weakly expressed, while FOXO4 and DCDC2 were prominently expressed in OGD/R-treated HCN-2 cells. Smurf2 overexpression promoted LDH release, reduced NLRP3, GSDMD-N, and cleaved-caspase-3 proteins, and decreased IL-1β and IL-18 concentrations. Sumrf2 improved the ubiquitination level of FOXO4 to downregulate its protein level. FOXO4 is bound to the DCDC2 promoter to facilitate its transcription. Overexpression of FOXO4 or DCDC2 reversed the inhibition of Smurf2 overexpression on pyroptosis of OGD/Rtreated HCN-2 cells.

Conclusion: Smurf2 overexpression facilitated the ubiquitination of FOXO4 to reduce its protein level, thereby suppressing DCDC2 transcription and restricting OGD/R-induced pyroptosis of cortical neurons.

]]> <![CDATA[Targeting the AKT/mTOR/p70S6K Pathway for Oligodendrocyte Differentiation and Myelin Regeneration in Neurological Disorders]]>https://eurekaselect.com/article/1347882023-12-29 Background: The AKT/mTOR/p70S6K pathway has been shown to potentially promote spinal cord injury (SCI) repair in rats. However, its exact mechanism and beyond needs to be further explored.

Objective: This study aims to explore the AKT/mTOR/p70S6K pathway in oligodendrocyte precursor cell (OPC) differentiation, microglial polarization differentiation, and the role of these in myelin regeneration in vitro.

Methods: The isolation, induction and characterization of rat primary neuronal stem cells, OPCs and oligodendrocytes were investigated with immunofluorescence and RT-qPCR. Then, the role of AKT/mTOR/p70S6K signaling was explored using western blotting and immunofluorescence, the effect on myelination was examined with OPC-dorsal root ganglion (DRG) neurons co-culture, and the influence of M1/M2 polarization status of microglia on myelin formation was also observed by adding M1/M2 supernatants into OPC-DRG neurons co-culture.

Results: Activation of the AKT/mTOR/p70S6K pathway elevated the expression of oligodendrocyte differentiation markers, including MBP, PLP and MOG, which also promoted the colocalization of MBP and NFH in OPC-DRG neurons co-culture. More interestingly, stimulation of the AKT/mTOR/p70S6K pathway facilitated M2 polarization of rat microglia. M2 polarization of microglia enhanced OPC differentiation to oligodendrocytes and myelin formation.

Conclusion: Our findings highlight the potential of targeting the AKT/mTOR/p70S6K pathway in promoting oligodendrocyte differentiation and myelin regeneration in neurological disorders such as SCI.

]]> <![CDATA[Pan-Immune-Inflammatory Value Predicts the 3 Months Outcome in Acute Ischemic Stroke Patients after Intravenous Thrombolysis]]>https://eurekaselect.com/article/1355842023-12-29 Background and Purpose: Immune and inflammatory response plays a central role in the clinical outcomes of stroke. This study is aimed to explore the clinical significance of the new inflammation index named pan-immune-inflammation value (PIV) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis therapy (IVT).

Methods: Data were collected from 717 patients who received IVT at the First Affiliated Hospital of Soochow University. Baseline data were collected before intravenous thrombolysis. Multivariate logistic regression analysis was used to assess the association between PIV and 3 months clinical outcome after intravenous thrombolysis. We also used receiver operating characteristic (ROC) curves analysis to assess the discriminative ability of PIV, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in predicting 3 months poor outcome.

Results: Of 717 patients, 182 (25.4%) patients had poor outcomes at 3 months. Patients with 3 months of poor outcome had significantly higher PIV levels compared to those with favorable outcomes [316.32 (187.42-585.67) vs. 223.80 (131.76-394.97), p < 0.001)]. After adjusting for potential confounders, the risk of 3 months of poor outcome was significantly higher among patients whose PIV fell in the third quartile (244.21-434.49) and the fourth quartile (> 434.49) than those in the first quartile (< 139.93) (OR = 1.905, 95% CI: 1.040-3.489; OR = 2.229, 95%CI: 1.229-4.044). The area under the ROC curve of PIV to predict 3 months of poor outcome was 0.607 (95%CI: 0.560-0.654; p < 0.001). The optimal cut-off values of PIV were 283.84 (59% sensitivity and 62% specificity).

Conclusion: The higher levels of PIV were independently associated with 3 months of poor outcomes in AIS patients receiving IVT. PIV like other inflammatory factors (PLR, NLR, and SII), can also predict adverse outcomes after IVT in AIS patients.

]]> <![CDATA[The Effect of Remote Ischemic Postconditioning on Quality of Life and Clinical Events after an Ischemic Stroke]]>https://eurekaselect.com/article/1364782023-12-29 Objectives: Repeated remote ischemic postconditioning (rIPostC) may be an easily applicable treatment following ischemic stroke to improve quality of life (QoL) and clinical outcomes. rIPostC consists of repeated, brief periods of limb ischemia (through inflation of a blood pressure cuff), followed by reperfusion. This study investigated the 1-year follow-up of rIPostC on QoL and clinical events.

Methods: As part of a randomized controlled trial, adult patients with an ischemic stroke within 24 hours after onset of symptoms were randomized to repeated rIPostC or sham-conditioning. rIPostC was applied twice daily during hospitalization (maximum of 4 days). QoL and patientreported outcome measures (PROMs) were assessed at 12-week and 1-year follow-ups. Additionally, we explored the effect of repeated rIPostC on clinical events (recurrent cerebrovascular events, hospitalization, and mortality).

Results: The trial was preliminarily stopped due to limitations in recruitment after the inclusion of 88 patients (rIPostC: 40; sham-conditioning: 48) (70 years, 68% male). Questionnaires were returned by 69 (78%) and 63 (72%) participants after 12 weeks and 1 year, respectively. The median difference of the stroke-specific QoL between rIPostC and sham-conditioning was 0.05 (p =0.986) and -0.16 (p =0.654) after 12 weeks and 1-year, respectively. No significant effect of rIPostC on the different domains of PROMs was detected. We observed no between-group differences in recurrent cerebrovascular events, hospitalization, or all-cause mortality (Hazard Ratios p >0.05).

Conclusion: In this exploratory analysis, we observed no significant difference between repeated rIPostC and usual care on QoL and clinical outcomes at 12 weeks and 1 year in patients with an ischemic stroke.

Clinical Trial Registration Number: NTR6880.

]]> <![CDATA[Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-reperfusion Injury by Down-regulating Mir-155-5p]]>https://eurekaselect.com/article/1340912023-12-29 Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has been studied, but the regulation of EP on miR-155-5p has not been reported.

Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury in vitro.

Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation, inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.

Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the YY1/p53/miR-155-5p axis.]]> <![CDATA[Bone Marrow Mesenchymal Stem Cell Exosomal miR-345-3p Ameliorates Cerebral Ischemia-reperfusion Injury by Targeting TRAF6]]>https://eurekaselect.com/article/1342822023-12-29 Introduction: The purpose of this study was to investigate the effects of bone marrow mesenchymal stem cells (BMSCs) exosomal miR-345-3p and tumor necrosis factor receptorassociated factor 6 (TRAF6) on cerebral ischemia reperfusion (CIR) injury. Exosomes (Exos) derived from BMSCs were isolated and identified. PC12 (rat pheochromocytoma) cells were used to establish an oxygen and glucose deprivation/reoxygenation (OGD/R) model.

Methods: Cell counting kit-8, TUNEL staining, lactate dehydrogenase staining, RT-qPCR, and western blotting were utilized for analyzing the functions of miR-345-3p about PC12 cells. Dualluciferase reporter experiment was then to confirm the link between miR-345-3p and TRAF6. Finally, using male SD rats, the middle cerebral artery occlusion (MCAO) model was constructed. Regulation of I/R damage in MCAO rats of miR-345-3p and TRAF6 were further explored in the changes of modified neurological severity score, cerebral infarction pictures, relative infarct volume, and histopathological changes. After OGD/R treatment, neuronal apoptosis was dramatically increased. After treatment with exosomal miR-345-3p, OGD/R-induced neuroapoptosis was dramatically inhibited. Exosomal miR-345-3p inhibited OGD/R-induced neuroapoptosis by downregulating the expression of TRAF6. However, the miR-345-3p inhibitor aggravated the changes caused by OGD/R.

Results: The corresponding regulations of miR-345-3p were reversed with TRAF6 overexpression. The animal experiments in vivo further verified that miR-345-3p ameliorated brain I/R injury in MCAO rats by targeting TRAF6.

Conclusion: This study found that BMSCs-exosomal miR-345-3p protected against CIR injury by decreasing TRAF6.]]> <![CDATA[Assessment of the Roles of Magnesium and Zinc in Clinical Disorders]]>https://eurekaselect.com/article/1363412023-12-29