Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

Case report: Coexistence of triple-seronegative myasthenia gravis and pathology-proven cryptogenic organizing pneumonia.

Objective: Emerging evidence shows that patients with myasthenia gravis (MG) were at a higher risk for the co-occurrence of other autoimmune diseases, which reflects phenotypic heterogeneity in MG. The coexistence of MG and cryptogenic organizing pneumonia (COP) has rarely been reported. The present case is to report the coexistence of triple-seronegative MG and pathology-proven COP in a patient. Methods: The clinical data of the patient were derived from medical records of Nanjing First Hospital, Nanjing Medical University, China. Written informed consent was obtained from the patient. Results: We presented a 56-year-old man with acute respiratory syndrome, who was diagnosed with COP based on the intra-alveolar fibroinflammatory buds (Masson's bodies) in the pathology of bronchoscopy biopsy. Oral prednisone induced dramatic symptomatic improvement and complete resolution of previous lung lesions. After a stable course of no respiratory symptom for 2 months, he was referred to the neurology department with complaints of fluctuating generalized muscle weakness. He was diagnosed with triple-seronegative MG based on fluctuating weakness, neostigmine test-positivity and RNS-positivity. After three-month treatment with pyridostigmine in combination with tacrolimus, the symptoms gradually improved and he achieved minimal symptom expression. Conclusions: This case highlights the rare coexistence of triple-seronegative MG and pathology-proven COP. However, a causal association between COP and MG cannot be explicitly ascertained. In future, more data are needed to clarify the relationship, taking into account the limited number of cases reported with this coexistence of the diseases.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

FLAIR vascular hyperintensity predicts early neurological deterioration in patients with acute ischemic stroke receiving endovascular thrombectomy.

Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently observed in patients with acute ischemic stroke (AIS). FVH is associated with functional outcome at 3 months in AIS patients receiving endovascular thrombectomy. In the present study, we assessed whether FVH predicted early neurological deterioration (END) and hemorrhagic transformation (HT) within 72 h in AIS patients receiving endovascular thrombectomy. We retrospectively analyzed 104 patients with acute internal-carotid-artery or proximal middle-cerebral-artery occlusion within 16 h after symptom onset. Before thrombectomy, all patients underwent brain magnetic resonance imaging. END was defined as an increase of 4 points or more from baseline National Institutes of Health Stroke Scale (NIHSS) during 72 h following onset. HT was assessed by brain computed tomography. Statistical analyses were performed to predict END and HT. The proportion of high FVH score, high American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grade in non-END group was higher than that in END group (p < 0.001, p < 0.001, respectively). FVH score was positively correlated with ASITN/SIR grade (r = 0.461, p < 0.001). FVH score was a predictor factor for END (adjusted OR, 13.552; 95% CI, 2.408-76.260; p = 0.003), while FVH score was not a predictor factor for HT. Furthermore, NIHSS at admission (adjusted OR, 1.112; 95% CI, 1.006-1.228; p = 0.038) and high-density lipoprotein cholesterol (adjusted OR, 18.865; 95% CI, 2.998-118.683; p = 0.002) were predictor factors for HT. To assess FVH score before thrombectomy might be useful for predicting END in AIS patients receiving endovascular thrombectomy.

Hybrid PET-MRI for early detection of dopaminergic dysfunction and microstructural degradation involved in Parkinson's disease.

Dopamine depletion and microstructural degradation underlie the neurodegenerative processes in Parkinson's disease (PD). To explore early alterations and underlying associations of dopamine and microstructure in PD patients utilizing the hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI). Twenty-five PD patients in early stages and twenty-four matched healthy controls underwent hybrid 18F-fluorodopa (DOPA) PET-diffusion tensor imaging (DTI) scanning. The striatal standardized uptake value ratio (SUVR), DTI maps (fractional anisotropy, FA; mean diffusivity, MD) in subcortical grey matter, and deterministic tractography of the nigrostriatal pathway were processed. Values in more affected (MA) side, less affected (LA) side and mean were analysed. Correlations and mediations among PET, DTI and clinical characteristics were further analysed. PD groups exhibited asymmetric pattern of dopaminergic dysfunction in putamen, impaired integrity in the microstructures (nigral FA, putaminal MD, and FA of nigrostriatal projection). On MA side, significant associations between DTI metrics (nigral FA, putaminal MD, and FA of nigrostriatal projection) and motor performance were significantly mediated by putaminal SUVR, respectively. Early asymmetric disruptions in putaminal dopamine concentrations and nigrostriatal pathway microstructure were detected using hybrid PET-MRI. The findings further implied that molecular degeneration mediates the modulation of microstructural disorganization on motor dysfunction in the early stages of PD.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

Admission blood cell counts are predictive of stroke-associated infection in acute ischemic stroke patients treated with endovascular therapy.

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.

Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.

The association between hyperglycemia and the prognosis of acute spontaneous intracerebral hemorrhage.

OBJECTIVE: To evaluate the potential association between the plasma glucose levels and the 90-day prognosis in patients with spontaneous intracerebral hemorrhage (sICH). METHODS: Patients with a well-defined diagnosis of sICH admitted within 24 h of onset were included. Random plasma glucose at admission and fasting plasma glucose on the following day were measured. Hyperglycemia was defined as a random plasma glucose ≥10 mmol/L or a fasting plasma glucose ≥7 mmol/L. Neurological severity at admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Functional outcomes were evaluated using modified Rankin Score (mRS) at three months after onset. Potential correlations between plasma glucose levels and neurological severity or functional outcomes values were assessed on Spearman's correlation analysis. Multivariable logistic regression analyses were performed to identify whether there were independent risk factors for 90-day outcomes after sICH. RESULTS: 228 consecutive adult patients with a mean age of 62.4 ± 12.9 years were prospectively enrolled. No significant association was observed between the random glucose levels (r = 0.108, p = 0.146) or fasting glucose levels (r = 0.116, p = 0.098) with functional outcomes at 90 days after discharge. However, hyperglycemia was associated with the neurological severity of sICH, both random glucose levels （r = 0.183, p = 0.009）and fasting glucose levels (r = 0.133, p = 0.045). On logistic regression analyses, age and NIHSS values at admission were independently associated with poor outcomes. CONCLUSION: Hyperglycemia was associated with neurological severity of sICH, but not with 90-day outcomes.

TREM2 p.H157Y Variant and the Risk of Alzheimer's Disease: A Meta-Analysis Involving 14,510 Subjects.

We recently revealed that p.H157Y (rs2234255), a rare coding variant of triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer's disease (AD) susceptibility in Han Chinese. Contrastingly, although p.H157Y was previously identified in both AD cases and controls by several sequencing studies, no association of this variant with disease susceptibility was reported. To gain a credible conclusion on the association between p.H157Y and AD risk, a meta-analysis involving 7,102 cases and 7,408 controls was conducted. Our results indicated that p.H157Y was associated with an increased risk of AD (OR=3.65, 95% CI: 1.61-8.28; P=0.002), further establishing TREM2 as an important susceptibility gene for this disease.

Independent Correlation of Serum Homocysteine with Cerebral Microbleeds in Patients with Acute Ischemic Stroke due to Large-Artery Atherosclerosis.

BACKGROUND AND AIM: The severity of cerebral microbleeds (CMBs) affected the prognosis of patients with acute cerebrovascular disease. Considering the impact of CMBs on clinical decision, it is necessary to assess the risk factors of CMBs. We aimed to evaluate the independent risk factors of CMBs in patients with acute ischemic stroke of large-artery atherosclerosis. MATERIALS AND METHODS: 112 patients were enrolled in the study. The baseline information, the results of laboratory examination and cranial MRI were collected. The independent risk factors of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis were evaluated. RESULTS: CMBs were found in 56 (50%) patients. Older age and higher homocysteine (Hcy) level were associated with an elevated chance of occurrence of CMBs. Further, there was a positive correlation between CMBs grade and serum Hcy level. CONCLUSIONS: Serum Hcy level is strongly associated with the presence of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis. Serum Hcy level may be a potential therapeutic target for alleviating adverse clinical outcomes of CMBs.

Common Polymorphisms Within QPCT Gene Are Associated with the Susceptibility of Schizophrenia in a Han Chinese Population.

A recent genome-wide association study conducted in Caucasians has identified glutaminyl-peptide cyclotransferase (QPCT) gene as a susceptibility gene for schizophrenia, as its common single nucleotide polymorphism (SNP) rs2373000 was significantly associated with the risk of this disease. To date, this finding has not been validated in other populations or ethnic groups. The aim of this study was to investigate the association of common SNPs spanning QPCT gene with the susceptibility of schizophrenia in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. A total of 6 tagSNPs including rs2373000 was selected and then genotyped in our sample. Although the relation between rs2373000 and the risk of schizophrenia was not successfully replicated, we showed for the first time that the minor allele (C) of rs3770752 was associated with a reduced risk of schizophrenia (odds ratio (OR) = 0.645; 95 % confidence interval (CI) 0.486-0.855; P corrected = 0.012) in our cohorts. Meanwhile, this allele seemed to modify the schizophrenia risk through a dominant manner (CC + CT vs. TT, OR = 0.625; 95 % CI 0.457-0.854; P corrected = 0.03). In addition, we found that the minor allele (T) of rs3770748 remarkably reduced the schizophrenia risk via a recessive manner (TT vs. TC + CC, OR = 0.618; 95 % CI: 0.449-0.851; P corrected = 0.03). Taken together, these findings demonstrate a significant association between common SNPs within QPCT gene and schizophrenia risk in a Han Chinese population, suggesting QPCT gene may represent a susceptibility gene for this disease.

Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer's Disease.

As a recently identified bioactive peptide of brain renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)] along with its metabolic enzyme angiotensin-converting enzyme (ACE) 2 and its receptor Mas forms ACE2/Ang-(1-7)/Mas axis. Accumulating evidence suggests an essential role of ACE2/Ang-(1-7)/Mas axis in maintaining normal cognitive functions in both animals and human subjects, and dysregulation of this axis contributed to the pathogenesis of several neurodegenerative diseases such as hypertension-induced neurodegeneration and vascular dementia. To date, whether this axis was associated with the etiology and progression of Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, remains unclear. In the current study, by using senescence-accelerated mouse prone 8 (SAMP8) mice, an animal model of sporadic AD, we showed for the first time that the level of Ang-(1-7) in the brain was significantly reduced during disease progression. More importantly, an inverse correlation was found between Ang-(1-7) level and tau hyperphosphorylation, a pathological hallmark of AD, in cerebral cortex and hippocampus of SAMP8 mice. Meanwhile, this has been further confirmed in P301S mice, an animal model of pure tauopathy. All these findings suggested that Ang-(1-7), the main effector of brain ACE2/Ang-(1-7)/Mas axis, might be implicated in the etiology and progression of AD, possibly via modulation of tau hyperphosphorylation.

ABCB1 hypomethylation is associated with decreased antiplatelet effects of clopidogrel in Chinese ischemic stroke patients.

Current predictive models including the CYP2C19 polymorphism and clinical factors still explain only about 12% of variability of clopidogrel responsiveness. Up until recently, the precise mechanism of clopidogrel resistance remains unclear. P-glycoprotein (P-gp) encoded by ABCB1, a transmembrane calcium-dependent efflux pump for clopidogrel, implicated a role in clopidogrel resistance. In this present study, we investigated the methylation status of ABCB1 gene promoter in relation to ABCB1 mRNA expressions and the antiplatelet effects of clopidogrel. This study was a prospective cohort analysis of eligible stroke patients (n = 183, aged 18-75 years) who received clopidogrel (75 mg/day) for at least 5 days before discharge. A final subcohort of 87 patients with CYP2C19*1/*1 genotype were enrolled in the study population. Patients were grouped in quartiles of maximum platelet aggregation (MPA values (Q1, Q2, Q3 and Q4, MPA(Q1) < 14.1%, MPA(Q4) > 35.4%). The methylation status of the ABCB1 promoter was 1.8 times in the Q1 MPA group (10.1 ± 2.4%) than in the Q4 MPA group (5.5 ± 2.1%) (P < 0.001). ABCB1 methylation correlated inversely with MPA (R = - 0.764, P < 0.001) and mRNA expression (R = - 0.839, P < 0.001). Results of a multivariate linear regression model demonstrated that ABCB1 methylation was independently associated with MPA (ß(coef ficient) = - 4.71, P < 0.001). ABCB1 expression was 0.62 times in the Q1 MPA group (5.3 ± 1.4 per thousand) than in the Q4 MPA (8.5 ± 2.5%o), and the expression of ABCB1 correlated positively with ADP-induced MPA (R = 0.791, P < 0.001). ABCB1 promoter methylation status in whole blood appears to be inversely associated with ABCB1 mRNA expressions and MPA. In conclusions, hypomethylation of ABCB1 promoter is associated with a decreased response to clopidogrel in ischemic stroke patients via increased ABCB1 mRNA expression.

The effects of previous statin treatment on plasma matrix metalloproteinase-9 level in Chinese stroke patients undergoing thrombolysis.

It is unclear whether previous statin therapy influences the prognosis, hemorrhagic transformation, and plasma matrix metalloproteinases (MMP)-9 levels in Chinese stroke patients receiving intravenous thrombolysis. We conduct a prospective cohort study of 193 patients treated with intravenous thrombolysis. All the enrolled patients were divided into 2 groups (the control group and the statin group), according to the previous history of statin use. The plasma MMP-9 levels were detected before and at 6 hours, 12 hours, 24 hours, and 72 hours after intravenous thrombolysis. The clinical outcome of stroke was measured in terms of the functional outcome and occurrence of symptomatic intracerebral hemorrhage. The MMP-9 levels increased after thrombolysis in statin group and control group. No significant intergroup difference was found in the MMP-9 levels before and at 6 hours after thrombolysis, but the levels were significantly lower in the statin group than in the control group at 12, 24, and 72 hours (P < .001) after thrombolysis. Similarly, no significant intergroup difference was noted in the occurrence of symptomatic intracranial hemorrhage as was the case with the modified Rankin scale (assessed by the Mann-Whitney U test) at 7 days (P = .428) and 90 days (P = .419) after thrombolysis. Our results indicate that pretreatment with statin can inhibit the thrombolysis-induced increase in plasma MMP-9 levels but does not significantly affect the prognosis of acute ischemic stroke patients undergoing intravenous thrombolysis.

Sex differences in clinical characteristics and outcomes after intracerebral haemorrhage: results from a 12-month prospective stroke registry in Nanjing, China.

BACKGROUND: There is uncertainty surrounding the differences in outcomes after intracerebral haemorrhage (ICH) between men and women. This study aimed to investigate the sex differences in clinical characteristics, severity and outcomes of Chinese ICH patients. METHODS: The Nanjing First Hospital stroke registry was a hospital-based registry of stroke patients with 1-year prospective follow-up. From 2004 to 2008, a total of 651 consecutively recruited patients with acute ICH were enrolled. Primary outcome was death or dependency defined as a modified Rankin Scale score of 3-6 at 12 months. Multivariable logistic regression analyses were performed to determine whether there were sex differences in clinical outcomes after ICH. Clinically important and biologically plausible risk factors of death or dependency were selected from available variables. RESULTS: A total of 615 ICH patients were enrolled. There was no significant difference in age (63.5 ± 14.0 vs. 62.7 ± 12.7, p = 0.500) between women and men. At baseline, men were more likely to be current smokers (46.1% vs. 3.6%, P < 0.001) or current drinkers (35.4% vs. 3.6%, P < 0.001), but women had higher admission National Institute of Health Stroke Scale (NIHSS) scores than men (10 vs. 8, P = 0.039). Women also had higher rates of death or dependency at 3, 6, and 12 months (61.2% vs. 46.8%, P = 0.001; 56.7% vs. 45.3%, P = 0.009; and 51.8% vs. 44.1%, P = 0.065; respectively). After adjustment for age, existing hypertension and diabetes, prior stroke, previous ischemic heart disease, previous atrial fibrillation, current smoking and alcohol consumption status, pre-stroke dependency, onset-to-door time, admission NIHSS score, admission systolic blood pressure and location of bleeding, the association between the female gender and death or dependency remained statistical significant at 3 months [odds ratio (OR): 1.76; 95% confidence interval (CI): 1.07-2.89], but did not reach statistical significance at 6 months (OR: 1.59; 95% CI: 0.99-2.54) and 12 months (OR: 1.22; 95% CI: 0.77-1.95). CONCLUSIONS: In a Chinese population, women are more likely to be dead or dependent early after ICH than men. However, this gender difference gradually attenuates over the period of 12 months.