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Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves electrophysiological and neurobehavioral outcomes following long-term recovery after cerebral ischemia and the possible contributions of lithium-mediated mechanisms of neuroplasticity.Male Sprague Dawley rats were subjected to right middle cerebral artery occlusion for 90 min, followed by 28 days of recovery. Lithium chloride (1 mEq/kg) or vehicle was administered via intraperitoneal infusion once per day at 24 h after reperfusion onset. Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treated with 2 or 20 μM lithium for 24 or 48 h; subsequent brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptosomal-associated protein-25 (SNAP-25) levels were analyzed using western blotting.Compared to controls, lithium significantly reduced infarction volume in the ischemic brain and improved electrophysiological and neurobehavioral outcomes at 28 days post-insult. In cultured cortical neurons, BDNF, GAP-43, and PSD-95 expression were enhanced by 24- and 48-h treatment with lithium after OGD.Lithium upregulates BDNF, GAP-43, and PSD-95, which partly accounts for its improvement of neuroplasticity and provision of long-term neuroprotection in the ischemic brain.

Peri-infarct depolarizations (PIDs) are spontaneous waves that propagate slowly across the penumbra region following stroke, contributing to secondary infarct growth and negatively affecting stroke outcomes. KThe Kir6.1 knockout (Kir6.1Much more PIDs appeared in Kir6.1This study shows that loss of Kir6.1, not Kir6.2 facilitates the induction of PIDs in focal cerebral ischemia, indicating that Kir6.1-forming channels in the brain may provide protection against PIDs.

Objective Ischemic stroke is a major cause of death in the global population, with a high disability and mortality rate. Lack of regenerative ability is considered to be the fundamental cause. This study aims to determine the effect of Shh pathway, which mediates regenerative signaling in response to CNS injury, on myelin repair and Olig1 expression in focal ischemic lesions in the rat. Methods A model of middle cerebral artery occlusion (MCAO) was established using the intraluminal suture method where the middle cerebral artery (MCA) was restricted for 120 min. Cyclopamine, a specific inhibitor of Shh, or saline was administered 12 h after MCAO surgery and lasted for 7 days. After MCA occlusion, male Sprague-Dawley rats were randomly allocated to cyclopamine- or saline-treated groups. A group of no-injection animals after MCAO were used as controls. The Shh signaling pathway, myelinogenesis-related factor MBP and Olig1 were testedby immunohistochemistry and RT-PCR assay. Results The levels of Shh and its component Gli1 were elevated from 1 d up to 14 d following ischemia, indicating that the Shh-Gli1 axis was broadly reactivated. Treatment with cyclopamine can partially block the Shh signaling pathway, prevent myelin repair, and decrease the Olig1 expression following ischemic stroke. Conclusion That blockade of Shh signaling concurrently with the creation of a lesion aggravated ischemic myelin damage, probably via its downstream effects on Olig1 transcription. Shh plays a contributory role during regeneration in the CNS, thereby providing promising new therapeutic strategies to assist in recovery from ischemic stroke.

Background and Purpose: Quantitative electroencephalogram (QEEG) parameters have been previously utilized in prognosis following acute ischemic stroke (AIS). However, the use and interpretation of QEEG parameters remain scarce following endovascular treatment (EVT) of AIS.Methods: AIS patients were prospectively enrolled following EVT, and 24-hour EEG monitoring was conducted. Global delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR), and relative band power were analyzed. Primary outcome was a poor outcome (modified Rankin Scale ≥4 at 90-day follow-up). Multivariate logistic regression and diagnostic analyses were performed.Results: Poor outcome was seen in 35.5% (11/31) of enrolled patients. Multivariable logistic regression identified that higher DAR (OR 1.10, 95% CI 1.02-1.18, p = 0.02) and higher DTABR (OR 1.13, 95% CI 1.01-1.27, p = 0.02) were associated with poor outcome. DAR ≥14.3 demonstrated high sensitivity (90.9%), specificity (90.0%) and accuracy (90.3%) for poor outcome.Conclusions: Early evidence of elevated DAR and DTABR on quantitative EEG was associated with poor outcome at 90 days following EVT for AIS.

Objectives Lithium exerts a broad neuroprotective effect on the brain. This study examined whether lithium exerts therapeutic effects on stroke by restoring neural connections at the ischemic core of cortices post brain insult. Methods We treated rats with lithium or vehicle (saline) every 24 h for the first 72 h, starting at the beginning of reperfusion after inducing middle cerebral artery occlusion (MCAO) in rats. Somatosensory evoked potential (SSEP) recording and behavioral testing were employed to evaluate the beneficial effects of lithium treatment. To examine the effects of lithium-induced neuroplasticity, we evaluated the dendritic morphology in cortex pyramidal cells and the primary neuronal cell culture that underwent brain insults and oxygen and glucose deprivation (OGD), respectively. Results The results demonstrated that rats subjected to MCAO had prolonged N1 latency and a decreased N1/P1 amplitude at the ipsilateral cortex. Four doses of lithium reduced the brain infarction volume and enhanced the SSEP amplitude. The results of neurobehavioral tests demonstrated that lithium treatment improved sensory function, as demonstrated by improved 28-point clinical scale scores. In vitro study results showed that lithium treatment increased the dendritic lengths and branches of cultured neurons and reversed the suppressive effects of OGD. The in vivo study results indicated that lithium treatment increased cortical spine density in various layers and resulted in the development of the dendritic structure in the contralateral hemisphere. Conclusion Our study confirmed that neuroplasticity in cortical neurons is crucial for lithium-induced brain function 50 recovery after brain ischemia.

Objectives: To investigate the factors affecting the risk of recurrent stroke after intracranial artery stenting.Methods: This is a subgroup analysis of a prospective single-arm registry study with 20 participating sites. Patients aged 18-85 years old with symptomatic intracranial atherosclerotic stenosis caused by 70-99% stenosis combined with poor collaterals were included in this study. The median follow-up in this study was 26.4 months.Results: A total of 260 patients were recruited in this study. Ischemic stroke related to target vessel occurred in 11 patients (4.2%) from 30 days to the last follow-up. The multivariate analysis revealed age ≥60 years old (OR: 11.991, 95% CI: 1.400-102.716; p = 0.023), no smoking (OR: 0.087, 95% CI: 0.010-0.787; p = 0.030), and Mori C type (OR: 5.129, 95% CI: 1.242-21.178; p = 0.024) retained significance in the model. There was no significant difference in the ischemic stroke based on medical history of hypertension, diabetes, dyslipidemia, baseline percent stenosis, length of stenosis, residual stenosis, and different stent types.Conclusions: Recurrence of ischemic stroke after intracranial stenting may be associated with elderly age, non-smoking, and Mori C type lesion. These factors will need to be monitored in future trials of intracranial stenting.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

Objective The aim of this study was to find out the relationship between serum biomarkers and cerebral collateral status in acute ischemic stroke with cerebral large artery atherosclerosis. Methods We enrolled patients with ischemic stroke due to large artery atherosclerosis within 7 days of symptom onset, age 18-80 years, from August 2016 to December 2017. Twelve biomarkers representing different pathophysiological mechanisms were tested after admission. Whole-brain perfusion combined with multiphase computed tomography angiography was performed to assess cerebral collateral structure and function. Results Fifty-two patients completed the test of candidate biomarkers and recruited in this study. The mean age was 55.0 (11.1) years, 42 (80.8%) patients were male, 20 (38.5%) had poor collateral, 36 (69.2%) patients had anterior circulation stenosis or occlusion. Compared with poor collateral group, the level of MMP-9 (135,475.00 pg/ml vs. 103,612.00 pg/ml, p = 0.040) and PGF (5.75 pg/ml vs. 3.46 pg/ml, p = 0.046) was significantly higher in good collateral group. The adjusted OR (95%CI) of MMP-9 and PGF were 5.533 (1.10-27.74, p = 0.038), 7.73 (1.41-42.39, p = 0.018), respectively. sTie-2 level had a positive correlation with proportion of Tmax 4-6 (r = 0.302, p = 0.033) and HMW-KGN had negative correlation with proportion of Tmax 6-8 (r = -0.338, p = 0.02). After adjustment, the correlation of sTie-2 level and proportion of Tmax 4-6 was statistically significant (p = 0.003), and correlation of HMW-KGN and Tmax6-8 was not statistically significant (p = 0.056). Discussion Serum PGF and MMP-9 levels may correlate with collateral status based on MP-CTA in acute ischemic stroke patients with cerebral large artery atherosclerosis. Higher PGF and MMP-9 concentration associated with good collateral status.

Objective Neural cell adhesion molecule L1CAM (L1) is involved in neuroprotection. To investigate a possible neuroprotective effect of L1 during ischemia, we determined whether blocking L1 with an antagonistic antibody would worsen the outcome of focal cerebral ischemia-reperfusion and increase blood-brain barrier (BBB) disruption. Methods Transient middle cerebral artery occlusion (MCAO) was performed in anesthetized rats. Five µg of antagonistic mouse IgG monoclonal L1 antibody 324 or non-immune control mouse IgG was applied on the ischemic-reperfused cortex during one hour of MCAO and two hours of reperfusion. At two hours of reperfusion, BBB permeability, size of infarct using tetrazolium staining, number of TUNEL-labeled apoptotic cells, and immunohistochemistry for expression of PTEN and p53 were studied. Results The antagonistic L1 antibody 324 increased the percentage of cortical infarct area (+36%), but did not affect BBB permeability in the ischemic-reperfused cortex. The antagonistic L1 antibody increased number of apoptotic neurons and p53 expression, but decreased PTEN expression. Conclusion Functional antagonism of L1 increases infarct size by increasing numbers of apoptotic neurons without affecting BBB permeability during the early stage of cerebral ischemia-reperfusion. Our data suggest that L1 affects primarily the brain parenchyma rather than BBB during early stages of cerebral ischemia-reperfusion and that endogenous brain L1 may be neuroprotective.

Thromboaspiration catheters are increasingly used for the endovascular treatment of large vessel stroke (LVS), while tortuous vascular anatomy still remains one major challenge in mechanical thrombectomy. Prompt assessing and understanding cavernous internal carotid artery (cICA) tortuosity may help to predict procedural complexities of mechanical thrombectomy and thus improve the clinical outcomes.A retrospective review was performed on a cohort of LVS patients with thromboaspiration catheter. Simplified classification of cICA tortuosity was applied by measurement of the angle of the posterior genus (P) and the height from the peak of the posterior genu to the trough of the anterior genu (D). Statistical analyses were performed to analyze differences among the obtained types of cICA tortuosity regarding procedural characteristics and clinical outcomes.A total of 150 patients with LVS proximal to the internal ICA terminus and middle cerebral artery (MCA) were included in this study, and three types of cICA tortuosity were defined by the simplified classification. The index, such as patients ages and hypertension, procedural fluoroscopy time, the degree of cICA tortuosity, first-pass success, final reperfusion, and 90-day mortality showed significant differences among the three types (The study indicated that the grading of cICA tortuosity is highly correlated with procedural complexity and clinical outcome in mechanical thrombectomy. The proposed classification system may be helpful in pre-procedure prognostication complexity and clinical outcomes.

Stroke, a cerebrovascular disease, has been introduced as the second cause of death and physical disability in the world. Recently, cell-based therapy has been considered by the scientific community as a promising strategy for reducing ischemic damages. The stem cells of the umbilical cord release growth and neurotrophic factors. The remarkable properties of these cells are the reason why they were selected as a potential candidate in the present research.In this study, the impact of transplanting umbilical cord stem cells on injuries resulting from ischemia was investigated. The male rats were categorized into three major. Using stereotaxic surgery, stem cells were injected to the right striatum of the brain. One week after transplantation, cerebral ischemic induction surgery was performed. The rats in the transplantation + ischemia group were separately divided into distinct sub-groups to explore the score of the neurological deficits, infarction volume, integrity of the blood-brain barrier, and brain edema.In this study, a significant decrease was observed in the neurological deficits of the transplantation + ischemia group compared with those of the control group. Similarly, the volume of infarction, the permeability of the blood-brain barrier, and edema were significantly reduced in the transplantation + ischemia group in comparison with those of the control group.The pretreatment of the transplanted umbilical cord stem cells in the striatum of ischemic rats possibly leads to restorative events, exerting a decreasing effect on cell death. Subsequently, these events may improve the motor ability and reduce ischemic injuries.

Radiological and clinical cerebral vasospasm (CV) is defined either as a delayed narrowing of cerebral arteries after aneurysmal subarachnoid hemorrhage (aSAH) or/and occurrence of new neurological deficit/worsening of Modified Glasgow coma score for 2 or more points. The objective of this study is to determine the presence and correlation between clinical and radiological presence of vasospasm in patients with aSAH.This study was designed as a clinical, prospective single center study at the Clinic of Neurosurgery, Clinical Center of Vojvodina, Novi Sad, Serbia. A total of 50 patients was included in the study after having radiologically confirmed aSAH. Intensity and region of CV was determined by CT and CTA performed both on admission and on day 9 of hospitalization, except for cases where clinical protocol required earlier imaging due to occurrence of clinical signs and symptoms of CV. In all patients, values of arterial blood pressure (PABP), headache (HA), body temperature (PBT), nonspecific behaviors (NSB), deterioration of consciousness (DC), new neurological deficit (NND), deterioration of two points or more per modified Glasgow Coma Scale (DmGCS ≥ 2) were monitored.CTA showed angiographic vasospasm detected in 100% patients with aSAH. Statistically significant positive correlation was found between the intensity of radiological CV and appearance of NND and DmGCS ≥ 2.This study confirms that CV always follows aSAH. Future research into pathophysiology of CV is needed in order to determine exact treatment strategies and targets so treatment towards zero mortality can be achieved.

Post-stroke autonomic nervous dysfunction measured with heart rate variability (HRV) is correlated with the traditional risk factors and poor outcome. This study aimed to investigate the association between HRV and infarct locations, etiology subtypes, and neurological functional outcomes in patients with acute ischemic stroke (AIS).In this prospective observational study, 186 consecutive patients were assigned to four major stroke severity categories based on the National Institutes of Health Stroke Scale score (NIHSS) and the modified Rankin Scale score (mRS): mild (NIHSS 0-4) stroke, moderate (NIHSS 5-14) stroke, 'favorable' (mRS 0-2) group, and 'unfavorable' (mRS 3-5) group. HRV time domain parameters were applied to evaluate the autonomic function of patients within 1 week after admission. All patients were classified into different etiology subtypes based on the TOAST (modified Trial of ORG 10172 in Acute Stroke Treatment) classification. The association of HRV with stroke location, etiology subtypes, neurological outcome was explored for all participants. Univariate and multivariate analyses were applied to explore the prediction value of HRV.160 participants had large artery atherosclerotic infarction (LAA), 61 had right internal carotid artery system infarction (R-ICA), and 61 had vertebrobasilar artery system infarction (VB). Root-mean-square of differences (RMSSD) of adjacent RR intervals and the proportion calculated by dividing the interbeat interval differences50 ms (pNN50) in patients of VB group was significantly lower than those of patients in R-ICA group (P 0.01). HRV parameters in the LAA group was significantly lower than non-LAA group (P 0.01). At discharge, significant lower HRV presented in the unfavorable group and moderate group (P 0.05). After logistic univariate and multivariate analysis, lower SDNN (OR = 1.019; 95% CI = 1.003-1.035;HRV measured after admission is related to the AIS infarction basin, TOAST subtypes, and neurological outcomes at discharge suggesting a possible role for HRV in evaluating AIS and identifying high-risk patients.

It has been established that poor outcomes in ischemic stroke patients are associated with the post-reperfusion inflammatory response and up-regulation of TLR4. Therefore, suppression of the TLR4 signaling pathway constitutes a potential neuroprotective therapeutic strategy. Schisandrin B, a compound extracted fromI/R: schemia/reperfusion; IL: interleukin; MCAO/R: middle cerebral artery occlusion and reperfusion; NF-κB: nuclear; TLR4: Toll-like receptor 4; TNF-α: tumor necrosis factor-α.

Following stroke, angiogenic strategy has been proposed to alleviate ischemia-induced injury by promoting angiogenesis and improving cerebrovascular function in the ischemic regions. Ligustilide (LGSL) is known to have neuroprotection against ischemic stroke-induced injury. But the effect of LGSL on promoting angiogenesis after ischemic stroke is unknown. The purpose of this study was to determine the effects of LGSL on neuroprotection and angiogenesis after stroke.BrdU cell proliferation assay, transwell, wound healing, and tube-formation experiments were performed to evaluate the effects of LGSL on mouse microvascular endothelial cells (bEnd.3). Male adult C57/BL6 mice were subjected to focal transient cerebral ischemia followed by intragastric LGSL administration. Immunostaining was performed to assess angiogenesis. VEGF level was assayed by ELISA. eNOS expression was performed by Western blot.LGSL significantly improved neurological function. LGSL promoted angiogenesisLGSL promoted focal angiogenesis and attenuated ischemia-induced brain injury, suggesting that LGSL is a potential agent that improves angiogenesis and promotes recovery from ischemic stroke.

We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism.Mice were divided equally into five groups: Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression.CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased.CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.

Aims: To compare the efficacy of ginkgolide in the treatment of Chinese patients with ischemic stroke between pre-marketing and post-marketing studies. Methods: This is a re-analysis of a pre-marketing (phase II/III, multicenter, double-blind, parallel-controlled; February 2005 to September 2005) and post-marketing (phase IV, multicenter, open, single-arm registration; April 2013 to June 2014) studies. The intervention groups received intravenous ginkgolide (10 mL daily, 14 days). Primary outcome was an improvement of National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores after 14 days. Results: In pre- and post-marketing studies, NIHSS and mRS scores all improved, compared to that of baseline (P < 0.001) in acute phase. Those factors significantly associated with △NIHSS after 14 days of therapy with ginkgolide were grouping (pre-marketing vs. post-marketing; OR 2.169, 95%CI = 1.462–3.216, P < 0.001), male (OR = 1.532, 95%CI = 1.152–2.037, P = 0.003), enrollment within 30 days after onset (OR = 1.915, 95%CI = 1.452–2.526, P < 0.001) and NIHSS score more than 8 points at baseline (OR = 15.140, 95%CI = 11.436–20.045, P < 0.001) after adjustment. Ginkgolide had a greater effect on patients in a relatively acute phase (time of onset to enrollment ≤30 days) and moderate-severe stroke (baseline NIHSS>8 points). Incidences of adverse reactions in the pre-marketing and post-marketing studies were 0.46% and 5.28%, respectively (P < 0.001). Conclusion: Intravenous ginkgolide may improve the outcome of acute ischemic stroke. Differences in effect between pre-marketing and post-marketing studies may be associated with gender, time of onset to enrollment and severity of stroke.

Background and aims: Trimethylamine N-oxide (TMAO), a pro-atherosclerotic intestinal microbiota metabolite, has mechanistic links to atherosclerosis development and cardiovascular diseases. In this study, we aimed to investigate whether serum TMAO levels could predict early neurological deterioration (END) after acute ischemic stroke.Methods: We prospectively recruited patients with first-ever ischemic stroke and hospitalized within 24 h of symptoms onset during Mar 2018 to Mar 2019. Plasma TMAO levels were quantified using stable isotope dilution high-performance liquid chromatography with tandem mass spectrometry after admission. END was defined as an increase in the total National Institutes of Health Stroke Scale by 2 or more points within 3 days.Results: Of the 362 patients included, END was diagnosed in 97 subjects (26.8%). The median TMAO concentrations were 4.8 μmol/L, with tertile levels as follows: first tertile ( 5.6 μmol/L). Patients with END showed higher levels of TMAO (median 5.0 vs. 4.5 μmol/L, P = 0.005) at admission. In univariate logistic analysis, elevated plasma levels of TMAO [odd ratios for highest tertile vs. lowest tertile, 2.14; 95% confidence interval, 1.19-3.82] was a significant predictor of END in patients with ischemic stroke. This association remained significant after controlling for confounders in multivariate logistic analysis. Multiple-adjusted spline regression model further confirmed the dose-response relationship between TMAO levels and END (P < 0.001 for linearity).Conclusions: Our study indicated that increasing TMAO levels at admission might be associated with END after acute ischemic stroke.

Few studies have examined the association between hemoglobin (Hb) levels and early neurological changes following acute ischemic stroke (AIS). The present research investigated whether higher or lower Hb level on admission was associated with early neurological deterioration (END) in AIS patients. Furthermore, we evaluated the predictive effect of Hb concentration on stable or improving outcome.In this prospective cohort study, a total of 1330 patients admitted within 24 hours after AIS onset were finally involved in the analysis. We classified participants into four groups according to baseline Hb levels: ≤120, 121-140, 141-160, and160 g/L. The risk of END was accessed by means of logistic regression analysis, and tendency of improvement and stability by multinomial logit analysis. We further evaluated the pattern and magnitude of association of Hb as a continuous variable and END by multivariate logistic regression analysis of restricted cubic spline.Compared with the reference group, hemoglobin160 g/L was associated with END (OR, 95%CI; 2.149, 1.314-3.512) and severe END (OR, 95% CI as 2.317, 1.351-3.976 and 2.810,1.589-4.968, respectively). Comparatively, higher Hb level also independently predicted improving (OR, 95% CI; 0.322, 0.170-0.609) and stable (OR, 95% CI; 0.371, 0.205-0.673) outcome. Similar results were found when restricted to anterior circulation ischemic stroke after adjustment of variables including large vessel disease.We concluded that patients with higher baseline Hb level are at significantly higher risk for END, and less likely to reach stable or improving status at the early stage of stroke.

To investigate the changes of prominent vessel sign (PVS) and susceptibility vessel sign (SVS) in acute ischemic stroke (AIS) patients with successful and non-successful vascular recanalization treatment, and to study the associations between the susceptibility-weighted imaging (SWI) findings and early clinical and imaging prognosis.Thirty-five patients with the acute MCA territory infarction were retrospectively included and classified into GroupThe mean PVSPVS and SVS changes are influenced by the success of vascular recanalization. However, the changes are unrelated to either early clinical or imaging outcomes in AIS patients. PVS-DWI mismatch can be taken as an imaging biomarker for early clinical outcomes, both for patients with or without successful vascular recanalization.

To identify predictors of functional outcome in patients with an anterior circulation large-vessel occlusion (LVO) in a setting of long transfer distances.Outcomes of LVO patients transferred for an endovascular thrombectomy (EVT) from North Karelia Central Hospital to Kuopio University Hospital between January 2018 and October 2019 were analysed using retrospective patient chart review.Three months after the stroke, modified Rankin Scale (mRS) was 0-2 in 20 of the 41 transferred patients. They were younger (66.7 vs. 74.2 years, p = 0.032) and had less severe stroke symptoms (National Institutes of Health Stroke Scale, NIHSS, 11.5 vs. 16.5, p = 0.029) than those with mRS 3-6. They also had the occlusion less often in M1 and more often in M2. EVT was performed in 32 patients (no differences between those treated with EVT and those not treated with EVT). Their median age was 73.0 years (interquartile range 65.5, 79.8; range 32-86; 25% over 80), mean NIHSS score 14.0 (standard deviation 5.9) and mRS eventually 0-2 in 44%. Only NIHSS was associated with mRS (OR = 1.16; p = 0.016) in the EVT-treated patients. mRS was 0 in 38% of all EVT-treated octogenarians but 4-6 in 83% of those with an internal carotid artery and/or M1 occlusion.Outcomes depended on stroke severity, age and vessel of occlusion. Prognosis was worse if the occlusion included M1, especially in octogenarians. Mothership and Drip-n-ship strategies should be compared in patients from remote locations stratified by stroke severity and patient age.

In ischemic stroke, reperfusion after thrombolysis is associated with secondary brain damage. Dihydromyricetin (DHM), a flavonoid, has shown neuroprotective effects through anti-oxidant, anti-inflammatory and anti-apoptotic properties. This study investigates the potential of DHM, given postreperfusion in middle cerebral artery occlusion (MCAo) model of stroke in rats.MCAo surgery was performed in male Wistar rats. Reperfusion was performed after 90 min of ischemia. DHM (50 and 100 mg/kg) was administered 10-15 min and 2 h postreperfusion followed by daily dosing for 2 more days. Neurobehavioral parameters and infarct size (TTC staining) were assessed after 72 h. The effective dose (100 mg/kg) was then used to study reduction in infarct size (measured by MRI) and effect on apoptosis (evaluated by protein expression of Bax, Bcl-2 and cleaved caspase-3 and TUNEL assay) in peri-infarct cortex. Furthermore, effects of DHM on neuronal damage and activation of astrocytes were studied by immunofluorescence.Poststroke DHM (100 mg/kg) administered for 3 days showed significant improvements in motor-coordination and infarct damage (TTC staining and MRI). MCAo-induced altered apoptotic proteins were normalized to a significant extent in peri-infarct cortex with DHM treatment. Data from TUNEL assay were complementary to the effects on apoptotic proteins. Additionally, DHM caused a significant reduction in the number of reactive astrocytes when compared with the MCAo group.This study demonstrated the efficacy of subacute DHM treatment in ischemia/reperfusion injury by modulating apoptosis and astrogliosis in the peri-infarct cortex. This suggests the potential of DHM in attenuating disease progression.

Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0-2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226-4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings.

Increasing evidence suggests that long noncoding RNAs can exert neuroprotective effects in cerebral ischemia-reperfusion injury. Levels of the long noncoding RNA ANRIL (ANRIL) are reportedly altered in ischemic stroke (IS) patients, but its role in IS requires further clarification. This study was designed to explore the mechanistic function of ANRIL in IS. In vitro, HT22 cells was treated with an oxygen-glucose deprivation/reperfusion (OGD/R). In vivo, brain ischemia/reperfusion was induced by 60-minute transient middle cerebral artery occlusion/ reperfusion (MCAO/R) IS model in C57/BL6 mice. Additionally, cells were transfected with si-ANRIL, pcDNA3.1-ANRIL, pcDNA3.1-NF-κB, or appropriate negative controls, and si-ANRIL and pcDNA3.1-NF-κB were administered into the lateral ventricles in MCAO/R model mice. Cell viability and apoptosis were detected via MTT and flow cytometry assays. mRNA and protein expression of NF-κB were detected via qRT-PCR and Western blotting. IL-1β, IL-6, TNF-a, and iNOS levels were detected via ELISA. In addition, infarcted area and neuronal injury were evaluated via TTC, Nissl, and immunofluorescent staining. We found that ANRIL knockdown increased cell viability and reduced apoptosis in vitro. Additionally, we found that ANRIL knockdown decreased p-P65, P65, IL-1β, IL-6, TNF-a, and iNOS levels, whereas these effects were reversed by NF-κB overexpression both in vitro and in vivo. Our results suggest that ANRIL knockdown attenuates neuroinflammation by suppressing the expression of NF-κB both in vitro and vivo model of IS, sugguesting that ANRIL might be a potentially viable therapeutictarget to diminish neuroinflammation in IS patients.

Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.

Objective: We aimed to evaluate the influence of a novel designed intensive patient care program (IPCP) on cognitive impairment, anxiety, depression and relapse-free survival (RFS) in acute ischemic stroke (AIS) patients. Methods: Two hundred forty-two AIS patients were consecutively recruited in this randomized controlled study and randomly allocated to IPCP group or control group as 1:1 ratio. Patients received IPCP and conventional treatment in IPCP group, while received usual education, cognitive rehabilitation training and conventional treatment in control group for 12-month intervention. Cognitive impairment, anxiety and depression were assessed by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS) anxiety (HADS-A), and HADS depression (HADS-D) at baseline (M0), month (M)3, M6 and M12. After intervention, patients were followed up until 2018/7/30 and RFS was calculated. Results: IPCP increased MMSE score at M12 and change of MMSE score (M12-M0), while decreased cognitive impairment rate at M12. For anxiety, decreased change of HADS-A score (M12-M0) and lower anxiety rate at M12 were observed in IPCP group compared to control group. For depression, decreased HADS-D score at M6 and M12, reduced change of HADS-D score (M12-M0) and lower depression rate at M12 were shown in IPCP group compared to control group. Besides, RFS was numerically longer in IPCP group compared to control group, but without statistical significance. Conclusions: IPCP presents with a positive influence on improving cognitive impairment and decreasing anxiety as well as depression, while a less effect on improving RFS in AIS patients. Abbreviation: IPCP: intensive patient care program; RFS: relapse free survival; AIS: acute ischemic stroke; MRA: magnetic resonance angiography; ITT: intention-to-treat; LOCF: last observation carried forward.

The damage caused by ischemic stroke is mostly refractory to medical therapies and amounts to a substantial degree of mortality and morbidity in the world. The core tenet of treatment for acute ischemic stroke (AIS) is to save 'reversible' ischemic tissue (ischemic penumbra) as quickly as possible within a limited therapeutic time window. The neuroprotective effect of hypothermia has been proven previously in a large number of animal experiments and clinical trials. Some of these animal and human studies have shown that pre-reperfusion hypothermia can reduce myocardial infarction and improve clinical outcomes. However, to date, there is little research about hypothermia before reperfusion in the animal model and human study of AIS. This review will explore possible benefits of the application of pre-reperfusion hypothermia in the setting of AIS.

The association between family history of stroke and clinical outcomes after ischemic stroke remains unclear.A total of 3878 acute ischemic stroke patients from CATIS were included. The participants with ischemic stroke were divided into groups according to types of family history of stroke, stroke onset age and stroke subtypes. The primary outcome was a composite outcome of death and vascular events within 1 year after stroke. Multivariable Cox proportional hazard models were used to analyze the association between family history of stroke and other variables and clinical outcomes.Among 3878 ischemic stroke patients, 708 (18.26%) had a history of stroke in their first-degree relatives and 399 experienced a composite outcome (172 patients died and 227 experienced vascular events) within 1 year after stroke. Overall family history was not associated with the primary outcome (HR, 1.08; 95% CI, 0.37-3.19). However, the patients with maternal stroke history (HR, 1.87; 95% CI, 1.31-2.97), stroke onset age55 years with family history (HR, 2.02; 95% CI, 1.08-3.80) and thrombotic stroke in the patients with family history (HR, 1.46; 95% CI, 1.00-2.12) were associated with primary outcome, death and vascular events, respectively.This study suggests that maternal stroke history, age55 years at stroke onset and thrombotic stroke in the patients with a family history are associated with poor outcomes after stroke. Further studies from other samples are needed to replicate our findings due to a reason for excluding some severe stroke patients in this study.

Preconditioning exercise can exert neuroprotective effects after stroke; however, the effects of exercise intensity, frequency, duration are unknown. We investigated the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats.Rats were divided into the following five groups: 5 times a week of exercise (5/w-Ex) group, 3 times a week of exercise (3/w-Ex) group, once a week of exercise (1/w-Ex) group, no exercise (No-Ex) group, and intact control (control) group. Rats were made to run on a treadmill for 30 min per day at a speed of 25 m/min for 3 weeks. After the running program, the rats were subjected to 60-min left middle cerebral artery occlusion. Two days after ischemia, the cerebral infarct volume, neurological and motor function, Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, expression of caspase-3, and TUNEL positive cells were examined in the cerebral cortex surrounding the ischemic zone.The 3/w-Ex and 5/w-Ex groups showed significantly reduced infarct volumes compared with the No-Ex group, but the 1/w-Ex group did not. In addition, the 3/w-Ex and 5/w-Ex groups had improved neurological scores and sensorimotor function compared with the No-Ex group. The Bax/Bcl-2 ratio, expression of caspase-3, and TUNEL-positive cells significantly decreased in the penumbra area in the 3/w-Ex or 5/w-Ex groups compared with the No-Ex group.Our findings suggested that three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke.TUNEL: terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick and labeling; MCAO:middle cerebral artery occlusion; BAX:Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; TTC: 2,3,5-triphenyltetrazorlium chloride.

Exposure to female estrous, a natural rewarding experience, alleviates anxiety and depression, and the contribution of this behavior to stroke outcome is unknown. The aim of this study was to evaluate whether exposure to female estrous is beneficial to recovery following transient ischemic stroke in male mice.Cerebral ischemia was induced in male ICR mice with thread occlusion of the middle cerebral artery (MCAO) for 30 min followed by reperfusion. MCAO mice were randomly divided into MCAO group and Estrous Female Exposure (EFE) group. The mice in the EFE group were subjected to estrous female mouse interaction from day 1 until the end of the experiment. Mortality was recorded during the investigation. Behavioral functions were assessed by a beam-walking test and corner test from day 1 to day 10 after MCAO. Serum testosterone levels were analyzed with ELISA, and the expression levels of growth-associated protein-43 (GAP-43) and synaptophysin in the cortex of the ischemic hemisphere were determined by western blot on day 7 after MCAO.Exposure to female estrous reduced the mortality induced by cerebral ischemic lesions. The beam-walking test demonstrated that exposure to female estrous significantly improved motor function recovery. The serum testosterone levels and ischemic cortex GAP-43 expression were significantly higher in MCAO male mice exposed to female estrous.Exposure to female estrous reduces mortality and improves functional recovery in MCAO male mice. The study provides the first evidence to support the importance of female interaction to male stroke rehabilitation.GAP-43: growth-associated protein-43; SYP: Synaptophysin; MCAO: middle cerebral artery occlusion; OVXs: ovariectomies; CCA: common carotid artery; ECA: external carotid artery; EFE: estrous female exposure; TTC: 2,3,5-triphenyltetrazolium chloride; PAGE: polyacrylamide gel electrophoresis; PVDF: polyvinylidene difluoride; ANOVA: analysis of variance; LSD: least significant difference.

AIMS The evidence of rt-PA intravenous thrombolysis in patients with minor ischemic stroke (MIS) is still controversial. This study aims to investigate the effect of rt-PA intravenous thrombolysis on the prognosis of patients with MIS. METHODS We continuously enrolled and analyzed patients with MIS admitted into our hospital within 24 h after symptom onset between January 2016 and December 2018, including 96 patients received intravenous thrombolysis within 4.5 h after symptom onset and 84 patients not received intravenous thrombolysis. A favorable long-term outcome was a 90-day mRS score of 0-1. Good short-term outcome was a 7-day NIHSS score of 0 or less than NIHSS onset. RESULTS There were no statistical differences between two groups of patients' age, gender, history of hypertension, coronary heart disease, atrial fibrillation, smoking, drinking, and baseline NIHSS score. Patients with history of stroke (22.62% vs. 10.42%, p

Background and aims Ischemic stroke (IS) is one of the leading causes of death and long-term disability in Bulgaria. IS affects different aspects of the patient's life and results in loss of independence and poor health-related quality of life (HR-QoL). We aimed to analyze the impact of IS on HR-QoL and to identify possible associations with sociodemographic, clinical features, and vascular risk factors (RF). Methods A prospective, hospital-based study was undertaken from 1 July 2019 to 31 June 2020, at a tertiary care referral center for neurological disorders in Bulgaria. A total of 150 patients with acute IS - 50 with thrombolytic and 100 with non-thrombolytic therapy - were included. Thorough clinical and sociodemographic data were collected. The NIHSS scale determined stroke severity, and HR-QoL was assessed with the Stroke Impact Scale Version 3.0 (SIS 3.0) during the first 3 months. Results The overall HR-QoL improved during the observation period, but still, it remained significantly worse. The major predictors of a marked reduction in HR-QoL were age, female sex, lower education level, and actively working at stroke onset, high NIHSS score, anterior circulation stroke, and more extended hospital. Atrial fibrillation and heart failure were significantly associated with poor HR-QoL. The other investigated vascular risk factors were associated with different extends with poorer HR-QoL, except for dyslipidemia. Conclusion Stroke survivors have significantly reduced HR-QoL. Multiple interacting factors are associated with an unfavorable outcome after IS. Early detection of these factors would help to improve the care for IS patients, to reduce disabilities and improve HR-QoL.

The prognostic value of uric acid in ischemic stroke remains controversial, and it is unclear whether renal function status modifies the prognostic value of uric acid in ischemic stroke patients.A total of 3284 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) with creatinine and uric acid measurements were included in this analysis. The primary outcome was a composite of death and major disability (modified Rankin Scale score ≥3) at 1 year after stroke.The prognostic value of uric acid in ischemic stroke was appreciably modified by patients' renal function status (The present study suggests that high serum uric acid concentration is associated with better prognosis in ischemic stroke patients with normal renal function, but not in those with abnormal renal function. The establishment of causality between increased uric acid levels and better stroke prognosis needs more suitably designed randomized clinical trials.

The endoplasmic reticulum stress (ERS) and ERS-related neuronal apoptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. (-)-Clausenamide has been reported to be nootropic and improve learning and memory in amnesia animal models. However, whether (-)-Clau could protect neurons from ischemic injury and the possible mechanism needed further study. The present study aimed to explore the effects of (-)-Clau on primary cortical neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R).Rat primary cortical neurons were used to set up an injury model of OGD/R which imitated the clinical I/R injury. Cell viability and apoptosis were measured by CCK-8 assay, LDH detection and TUNEL staining, respectively. The activation of GRP78/eIF2α-ATF4-CHOP signaling pathway, one of the three branches of ERS, and cleaved caspase-3, the apoptotic marker, were assessed by western blotting.OGD/R induced activation of GRP78/eIF2α-ATF4-CHOP signaling pathway. (-)-Clau significantly attenuated OGD/R-induced decrease in the cellular viability and the activation of GRP78, eIF2α, ATF4 and CHOP. To further confirm the effect of (-)-Clau on OGD/R-induced ERS activation, the ERS inducer Tunicamycin (TM) was applied. TM significantly abolished (-)-Clau's protective effect against ERS and neuronal apoptosis, indicating that the protective effect of (-)-Clau was dependent on inhibiting ERS.The present work demonstrated for the first time that (-)-Clau could reverse the activation of GRP78/eIF2α-ATF4-CHOP branch, thus inhibited ERS and the subsequent apoptosis induced by OGD/R and promoted cell viability in vitro. (-)-Clau could serve as a promising therapeutic agent in the treatment for ischemic stroke in the future.ATF4: activating transcription factor-4; ATF6: activating transcription factor-6; CHOP: transcriptional induction of CCAAT/enhancer binding protein homologous protein; (-)-Clau: 3-hydroxy-4-phenyl-5a-hydroxybenzylN-methyl-g-lactam; eIF2α: eukaryotic initiation factor 2α; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; GRP78: 78-kDa glucose regulated protein; I/R: ischemia/reperfusion; IRE1: inositol requiring enzyme-1; JNK: c-Jun N-terminal kinase; OGD/R: oxygen-glucose deprivation/reoxygenation; PERK: double-stranded RNA-dependent protein kinase-like ER kinase; TM: Tunicamycin; UPR: unfolded protein response.

Objectives: Intravenous thrombolysis and thrombectomy are recommended for patients whose stroke onsets are within first 6 h, and very few options are available for patients whose stroke onset is more than 6 h, which includes most ischemic stroke patients. Human urinary kallidinogenase (HUK) showed potential clinical benefits in acute ischemic stroke patients. This study aims to investigate the safety and clinical benefits of HUK in ischemic stroke patients.Patients and methods: Patients were recruited for a multicenter double-blind, placebo-controlled phase II b and phase III trial. Neurophysiological outcomes were assessed by the European Stroke Scale (ESS) and the functional outcomes were assessed by the activity of daily living scale (ADL). Safety was monitored by recording adverse events.Results: The improvements in ESS scores and ADL scores in the HUK group were significantly greater than that in patients receiving placebo. Furthermore, HUK treatment was also associated with a lower rate of disable, according to ADL. HUK-related adverse events occurred at a low rate, in 1.73% of HUK-treated patients.Conclusion: HUK is safe and provides potential clinical benefits as a treatment for acute ischemic stroke. Further large post-marketing observational studies are needed.

Objectives: This study aimed to assess the preoperative risk factor for perioperative ischemic stroke (PIS) in patients undergoing non-cardiovascular and non-neurological surgeries.Methods: Patients were retrospectively enrolled and grouped into two groups at a ratio of 1:2 according to their PIS status, i.e. patients with PIS in disease group, and patients without PIS in control group. Univariate analysis and multivariate logistic regression analysis were performed on admission laboratory test indices and preoperative risk factors for stroke. The pooled cohort equation (PCE), Essen Stroke Risk Score (ESRS), and Stroke Prognostic Instrument II (SPI-II) were used to separately assess the risk of stroke in patients with or without a history of stroke.Results: There were significant differences between the two groups in the levels of high-density lipoprotein cholesterol (HDL-C), prealbumin, renal insufficiency, dyslipidemia, coronary heart disease, anemia, and hemoglobin; the incidence of electrolyte disturbance; and previous histories of smoking, drinking, and stroke. Multivariate logistic regression analysis showed that renal insufficiency, histories of smoking and stroke, and decreased HDL-C can increase the risk of PIS. There were no significant differences between the disease group and the control group in ESRS or SPI-II score in patients with stroke history. There was a significant difference between the two groups in the risk of PIS evaluated by PCE in patients without stroke history.Conclusions: History of stroke and smoking, renal insufficiency, and low HDL-C are independent risk factors for PIS. It is feasible to assess the risk of stroke in preoperative patients using PCE in clinical practice.

Objective: Chronic inflammation is considered as playing an important role in the pathophysiology of atherosclerosis, but the exact contributing inflammatory pathway on stroke is not clear. We aimed to examine the causal association of inflammatory biomarkers, such as interleukin-1 receptor antagonist (IL-1Ra), soluble interleukin-6 receptor (sIL-6R) and C-reactive protein (CRP), with the risk of ischemic stroke and its subtypes.Methods: Two-sample mendelian randomization analyses were performed using IL-1Ra, sIL-6R and CRP related genetic variants as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the largest GWAS meta-analysis on stroke to date - the Multiancestry Genome-wide Association Study of Stroke (MEGASTROKE) consortium. Associations of IL-1Ra with stroke or its subtypes were estimated using inverse-variance weighted (IVW) method with SNPs rs6743376 and rs1542176 as instruments. Wald ratio method with SNP rs2228145 as the instrument was used for sIL-6R and IVW, MR-Egger, simple and weighted median approaches with 4- or 18-SNPs instruments were used for CRP.Results: Genetically elevated ln(IL-1Ra), ln(sIL-6R) and ln(CRP) levels were not causally associated with ischemic stroke (OR = 1.00, 95% CI: 0.97-1.04, p = 0.80; OR = 0.93, 95% CI: 0.87-0.99, p = 0.03; OR = 1.01, 95% CI: 0.94-1.09, p = 0.78). No significant association was observed between ln(IL-1Ra), ln(sIL-6R) and ln(CRP) level and ischemic stroke subtypes.Conclusions: Our study did not find convincing evidence to support that inflammatory biomarkers like IL-1Ra, sIL-6R and CRP are causally associated with the risk of ischemic stroke or its subtypes.

Leptin may be associated with cardiovascular disease. We tested to determine whether leptin is a marker for first-ever acute ischemic stroke (AIS) in a nested case-referent study.Consecutive patients with first-ever AIS from May 2017 to December 2017 were included. Referents were matched for sex, age and body mass index. Serum leptin levels and routine tests were examined in both groups.The median serum level of leptin in the stroke patients was 14.3 (interquartile range [IQR], 7.2-21.7) ng/ml, which was significantly higher (P 0.001) than in the referents (10.7; 5.7-13.6 ng/ml). There was a positive correlation between serum level of leptin and National Institute of Health Stroke Scale score (r[Spearman] = 0.43, P 0.001). In addition, serum leptin levels paralleled lesion size. Median serum level of leptin in patients with small lesions, medium lesions and large lesions was 7.3 (IQR, 5.3-14.3) ng/ml, 13.9 (IQR, 7.0-21.3) ng/ml, 20.5 (IQR, 12.4-32.7) ng/ml, respectively (analysis of variance: P 0.001). In the univariate model matching for sex and age, leptin as a continuous variable was associated with AIS, after adjustment for possible confounders (odds ratio [OR] 1.07, 95% confidence interval [CI]: 1.04-1.11; P 0.001). After adjusting for all other factors, leptin remained an independent stroke predictor with an adjusted OR of 1.03 (95% CI, 1.00-1.10; P = 0.006). Interestingly, the association between AIS and leptin level was more pronounced among men (adjusted OR = 1.05, 95% CI: 1.01-1.12; P 0.001) when compared with women (adjusted OR = 1.03, 95% CI: 1.10-1.11; P = 0.009).Serum leptin is associated with first-ever AIS, lesion size and stroke severity in a Chinese cohort.

Stroke is the leading cause of death worldwide and stenosis of the carotid artery accounts for more than half of all cases. Carotid duplex is an effective non-invasive ultrasound test which identifies stroke patients with moderate to severe carotid stenosis who are candidates for preventative intervention to reduce the risk of recurrence. In patients with moderate to severe carotid stenosis, reversed ophthalmic artery flow (ROAF) is often observed at the time of the carotid duplex scan. In this study, we investigated whether ROAF, denoting exhaustion of cerebral collateral flow in ischemic stroke patients affected mid-term functional outcomes following carotid artery stenting (CAS) procedures. In total, 144 consecutive patients with a first episode of ischemic stroke and subsequent CAS procedure conducted between January 2010 and November 2014 at Changhua Christian Hospital, Taiwan were included. Clinical data were obtained by medical record review. Disability was assessed at two time points by utilising the Barthel Index (BI) and modified Rankin Scale (mRS) before CAS and 12 months post-CAS. Among 85 patients presenting without ROAF, 48/85 (56.4%) had improved mRS scores following stenting. The condition remained unchanged (stationary) in 36/85 (43.5%) patients after stenting and one patient exhibited deteriorated condition 1/85(1.1%). In contrast, among the 59 patients presenting with ROAF, 24/59 (40.6%) had improved mRS score following stenting. The condition remained unchanged (stationary) in the remaining 35/59 (59.3%) patients after stenting, and no patient exhibited deteriorated condition 0/59 (0 %). This study provides evidence that CAS is a valid and effective treatment option regardless of whether patients exhibited ROAF or not. Patients without ROAF were significantly more likely to have improved mid-term functional outcomes compared to those with ROAF. In the group without ROAF admission, CRP may play a role in predicting subsequent functional outcomes, whereas admission Barthel Index was a predictor of outcome in the ROAF group.

Objectives: Oxidative stress is a known risk factor for the pathogenesis of atherosclerosis, the main cause of ischemic stroke. Glutathione S-transferase (GST) omega-1 and omega-2, members of phase II enzymes, play a role in the antioxidant system. The single nucleotide polymorphisms (SNPs), C419A and A424G in GST omega genes can cause a decrease in enzyme activity. The aim of this study was to investigate the possible association between these polymorphisms and ischemic stroke risk in a Turkish population. Methods: The genotypes and allele frequencies for 239 patients and 130 controls were determined by the PCR/RFLP method. No significant differences were found between patients and controls in terms of genotype and allele frequencies. Results: The frequency of the polymorphic ‘A’ allele was 0.358 in patients and 0.342 in controls for the C419A polymorphism in the GSTO1 gene. The frequency of the polymorphic ‘G’ allele for GSTO2 A424G SNP was 0.370 in patients and 0.404 in controls. The combined homozygous wild type genotype ‘CCAG’ was significantly higher in control group than in the patients. Conclusion: No significant difference was observed between the stroke patients and controls in terms of genotypes and allele distributions. Double combine haplotype CCAA was found to be protective against ischemic stroke when compare to other haplotypes. However, different genotypes of GSTO1 and GSTO2 were observed to have effects on stroke risk in subgroups of diabetics and smokers. In conclusion, the current study is the first to report this finding., Middle East Technical University Research Project Fund

The patterns and mechanisms underlying stroke in cancer patients differ from those of the conventional etiology. In this study, we further investigated the characteristics distinguishing cancer-associated ischemic stroke (CAIS) and the relationship of D-dimer value with CAIS.Sixty-one acute ischemic stroke patients with cancer (cancer group) and 76 stroke patients without cancer (control group) were recruited. Cerebrovascular distribution was divided into 3 circulations and 23 vascular territories, and acute multiple brain infarcts (AMBIs) were defined as discrete MRI diffusion-weighted imaging (DWI) lesions in1 vascular territory.Cancer patients had higher average D-dimer and fibrinogen degradation product values, and fewer stroke risk factors. The numbers of infarct-affected vascular territories, AMBIs, and AMBIs in multiple circulations were significantly higher in the cancer group. Receiver operating characteristic analysis showed that the cutoff value of D-dimer was 2.785 μg/ml; and above features were particularly evident in cancer patients whose D-dimer values were2.785 μg/ml, while those with D-dimer values ≤2.785 μg/ml were similar to controls.D-dimer2.785 μg/ml may be an effective cutoff value and a sensitive index for identifying CAIS patients. AMBIs in ≥3 vascular territories and AMBIs in both the anterior and posterior circulations are two imaging characteristics of CAIS.

There is no definitive data regarding the usefulness of Brain microbleeds (BMBs) as an imaging marker with homeostatic markers to predict intracerebral hemorrhage (ICH) and ischemic stroke risk to personalize decisions on anticoagulation in AF. In this study, we prospectively evaluated clinical, radiological homeostatic biomarkers and their association with stroke outcomes in 73 AF-related ischemic stroke patients.All BMBs were measured manually on Susceptibility-Weighted Imaging (SWI). The levels of NT-pro-BNP, hs-CRP, FVII, FVIII and vWF were studied as homeostatic markers. For all patients, we calculated CHADS2, CHA2DS2-VASc, HAS-BLED scores and modified Rankin Scale (mRS) scores. Functional independence and good clinical outcome were defined as a mRS score of 0-2.The mean age of the study population was 69.74 ± 9.79 years, and 36 patients were female. The leading vascular risk factor was hypertension (61%). BMBs were determined in 20 patients (27.4%) on SWI, 12 patients had less than five lesions. Presence of BMBs lesions on SWI was significantly associated with age and hypertension (p = .020) and congestive heart failure (p = .011). The median CHA2DS2-VASc score in patients was 4.96 ± 1.54. CHA2DS2-VASc score (p = .042), CHADS2 score (p = .037) and HAS- BLED score (p = .033) were significantly related with the presence of BMBs in the study patients. Among homeostatic markers, the levels of NT-pro-BNP, hs-CRP, and vWF were significantly associated with the presence of microbleeds (p = .013, p = .029, p = .020, respectively).Pathogenesis of AF is involved abnormal changes of hemostasis, endothelial dysfunction, antithrombotic state and inflammation. The homeostatic markers, which play role in these pathways, and the presence of BMBs could use to form a prognostic clinic assessment tool to predict bleeding risk.

Poststroke prognosis is associated with autonomic status. The purpose of our study was to determine whether percutaneous mastoid electrical stimulator (PMES) can alleviate abnormal heart rate variability (HRV) and improve clinical outcome.This prospective, randomized, double-blinded, placebo-controlled study enrolled a total of 140 patients with autonomic dysfunction within 3d after acute ischemic stroke. The patients were treated with PMES or sham stimulation once daily over a period of 2 weeks. HRV was primarily assessed by the fractal dimension (FD) at admission and 2 weeks. All patients were followed up for 3 months. The clinical outcome was death and major disability (modified Rankin Scale score≥ 3) at 3 months after acute ischemic stroke.FD of the 2-week treatment period increased in PMES groups. PMES can significantly alleviate abnormal HRV. The difference in FD of the 2-week treatment period between the PMES and sham groups was significant (1.14 ± 0.27 vs. 1.00 ± 0.23; P = 0.001). In fully adjusted models, PMES was associated with reduced 3-month mortality (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.93; P = 0.036). No significant group differences were seen in three major disability and composite outcome (P 0.05).PMES was a safe, effective, and low-cost therapy to alleviate HRV and could significantly reduce mortality in the early recovery phase after acute ischemic stroke.

OBJECTIVES Inflammation plays a key role in the pathogenesis and progression of ischemic stroke (IS). The high mobility group box 1 (HMGB1) nucleoprotein is involved in the amplification of inflammatory responses during acute ischemic injury. HMGB1 levels in patients with active disease are higher than those in healthy controls. We performed a meta-analysis to assess currently published data pertaining to circulating blood HMGB1 levels in IS and the relationship with stroke severity. METHODS We systematically searched for studies investigating the circulating blood HMGB1 levels in patients with IS in PubMed/Medline, Embase, the Cochrane Library, Web of science and China National Knowledge Infrastructure (CNKI). Two independent researchers used the Cochrane Collaboration tools for data extraction and quality assessment. Extracted data were analyzed by Review Manager version 5.3. RESULTS A total of 28 studies were included with a total of 4497 participants, including 2671 IS patients and 1826 matched controls. The meta-analysis revealed that compared with control, IS patients had higher circulating blood HMGB1 levels (n = 4497, standardized mean difference (SMD) = 5.70, 95%confidence interval (CI) = 4.79 to 6.62, Z = 12.23, P

To explore the potential effect of miR-125b on p53-mediated regulation of Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rats with cerebral ischemia-reperfusion (CIR) injury. Sprague-Dawley (SD) rats were used to conduct CIR injury and injected with miR-125b mimic/inhibitor or p53 inhibitor (Pifithrin-α, PFT-α). Dual-luciferase reporter gene assay was used to analyze the targeting relationship between miR-125b and p53. Longa scoring and Triphenyl tetrazolinm chloride (TTC) staining were used to test the neurologic function and determine infarct size, respectively. Hematoxylin-eosin (HE) and Nissl's stainings were conducted to observe the morphology of cortical neurons. Neuronal nuclei (NeuN) expression was detected by immunohistochemical staining. QRT-PCR was performed to detect the expressions of miR-125b and p53. TUNEL staining and Western blotting was used to determine neuronal apoptosis and expressions of Bax/Cytochrome C/Caspase-3 signaling pathway-related proteins, respectively. Our results showed that miR-125b could directly target p53. As observed, overexpression of miR-125b could obviously reduce the neurological score, infarct size, and brain water content after CIR in rats, which also improved the morphology of cortical neurons, increased the number of neurons, reduced neuronal apoptosis, and inhibited the expressions of Bax/Cytochrome C/Caspase-3 pathway. Moreover,the similar results were observed in rats with CIR after injected with PFT-α. But no significant differences in each index were found in CIR group and CIR + anti-miR-125b + PFT-α group.MiR-125b exerts protective effects on CIR injury through inhibition of Bax/Cytochrome C/Caspase-3signaling pathway via targeting p53, which is likely to be a promising treatment for CIR.3'-UTR: 3-untranslated region; CIR: cerebral ischemia-reperfusion; CIS: cerebral ischemic stroke; PFT-α: Pifithrin-α; PVDF: polyvinylidene fluoride; SD: Sprague-Dawley; TBST: tris buffered saline with tween. TTC staining: Triphenyl tetrazolinm chloride staining; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling.