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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(2): 175-183, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38531768

ABSTRACT

OBJECTIVES: To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia. METHODS: Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3 and a platelet count <100×109/L were obtained from a multicenter register. Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was a 1-year all-cause death. The short-term neurological outcomes were evaluated by modified Rankin scale (mRS) score at discharge. RESULTS: A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled. Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge (OR=1.657, 95%CI: 1.253-2.192, P<0.01) and did not increase the risk of intracranial hemorrhage (OR=2.359, 95%CI: 0.301-18.503, P>0.05), compared with those without antiplatelet therapy. However, dual-antiplatelet therapy did not bring more neurological benefits (OR=0.923, 95%CI: 0.690-1.234, P>0.05), but increased the risk of gastrointestinal bleeding (OR=2.837, 95%CI: 1.311-6.136, P<0.01) compared with those with mono-antiplatelet therapy. For patients with platelet counts ≤75×109/L and >90×109/L, antiplatelet therapy significantly improved neurological functional outcomes (both P<0.05). For those with platelet counts (>75-90)×109/L, antiplatelet therapy resulted in a significant improvement of 1-year survival (P<0.05). For patients even with concurrent coagulation abnormalities, mono-antiplatelet therapy did not increase the risk of various types of bleeding (all P>0.05) but improved neurological functional outcomes (all P<0.01). There was no significant difference in the occurrence of bleeding events, 1-year all-cause mortality risk, and neurological functional outcomes between aspirin and clopidogrel (all P>0.05). CONCLUSIONS: For non-cardioembolic mild stroke patients with thrombocytopenia, antiplatelet therapy remains a reasonable choice. Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.


Subject(s)
Platelet Aggregation Inhibitors , Stroke , Thrombocytopenia , Humans , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Thrombocytopenia/drug therapy , Thrombocytopenia/complications , Female , Male , Stroke/complications , Aged , Platelet Count , Middle Aged , Ischemic Stroke/drug therapy , Ischemic Stroke/complications , Intracranial Hemorrhages/chemically induced
2.
Front Neurol ; 15: 1272802, 2024.
Article in English | MEDLINE | ID: mdl-38327620

ABSTRACT

Background: Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms, but it can also lead to thrombotic events, including ischemic stroke. Case presentation: This report describes the case of a 52-year-old Chinese man who was admitted to the hospital twice due to recurrent cerebral infarction, characterized by sudden speech impairment and weakness in the right upper extremity. Brain MRI revealed multiple ischemic changes, predominantly in the left frontal and parietal lobes. Coagulation tests demonstrated reduced plasma fibrinogen (Clauss method), prolonged prothrombin time and thrombin time, and an elevated international normalized ratio. However, the ELISA assay indicated elevated levels of fibrinogen γ-chain protein. Despite a 2-month-old treatment regimen with aspirin, clopidogrel, and atorvastatin after the first hospitalization, the patient experienced a second ischemic stroke. Genetic analysis using whole-exome sequencing (WES) and Sanger sequencing identified a rare heterozygous missense variation, FGG c.952G>A (rs267606810), in both the stroke patient and his asymptomatic sister. Both individuals exhibited the same alterations in fibrinogen, characterized by reduced functional levels but increased antigenic protein. Subsequently, the patient was diagnosed with ischemic stroke associated with congenital dysfibrinogenemia. Conclusion: This case report expands the clinical phenotype spectrum associated with FGG c.952G>A (rs267606810) and underscores the significance of considering CD as a potential etiology for unexplained ischemic stroke, particularly in patients with a family history of coagulation disorders.

3.
J Alzheimers Dis ; 95(4): 1509-1518, 2023.
Article in English | MEDLINE | ID: mdl-37718807

ABSTRACT

BACKGROUND: Elevated tau phosphorylation has been linked to the Apolipoprotein E (APOE) ɛ4 allele, which is considered one of the most significant genes related to Alzheimer's disease (AD). However, it is uncertain whether the impact of increased plasma tau phosphorylated at threonine 181 (p-tau181) on memory and executive function decline would be greater among APOEɛ4 carriers. OBJECTIVE: To investigate the effects of plasma p-tau181 and APOEɛ4 on memory and executive function. METHODS: The longitudinal analysis included 608 older adults without dementia (aged 72±7 years; 47% female; follow-up period of 1.59±1.47 years) from the ADNI dataset, including 180 individuals with normal cognition and 429 individuals with mild cognitive impairment. Linear mixed-effects models were utilized to assess the contributions of APOEɛ4 status and plasma p-tau181 to longitudinal changes in memory composite score and executive function composite score. RESULTS: At baseline, the APOEɛ4+/Tau+ group exhibited poorer performance in memory composite score and executive function composite score, and an elevated load of cerebrospinal fluid Aß and tau pathologies. To further understand longitudinal changes, we compared groups directly based on plasma p-tau181 and APOEɛ4 status (four groups: APOEɛ4-/Tau-, APOEɛ4-/Tau+, APOEɛ4+/Tau-, APOEɛ4+/Tau+). Both the memory composite score and executive function composite score showed a significantly greater decline in the APOEɛ4+/Tau+ group than in all other groups. CONCLUSIONS: Our findings indicate that there is an interaction between plasma p-tau181 levels and APOEɛ4 status, which contributes to the longitudinal changes of memory and executive function in older adults without dementia.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Female , Aged , Male , Executive Function , Biomarkers/cerebrospinal fluid , Alzheimer Disease/genetics , Alzheimer Disease/cerebrospinal fluid , Cognitive Dysfunction/genetics , Cognition , tau Proteins/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid
4.
Prev Med Rep ; 35: 102340, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37576842

ABSTRACT

Stroke is characterized by high morbidity, high mortality and high disability rate, which is a major health problem worldwide. However, most community-based studies report a lack of public knowledge related to stroke. The aim of this study is to investigate stroke-related knowledge and prevention practices among stroke patients in Taizhou, China. A face-to-face survey was conducted and questionnaires were completed by 156 S patients from June 27 to August 30, 2022. A generalized linear model was applied to explore the factors influencing prevention practices. Among the total participants, 36.5% and 40.4% of them had good knowledge of the stroke-related warning signs and risk factors, respectively. Participants who had good stroke prevention practices accounted for 57.7%. The higher score of stroke-related knowledge among inpatients, the better their prevention practices (B = 0.16, 95 %CI: 0.05 âˆ¼ 0.28). In addition, those with age ≥ 60 (B = 1.20, 95 %CI: 0.42 âˆ¼ 1.97), females (B = 0.93, 95 %CI: 0.24 âˆ¼ 1.61), having physical activities (B = 1.01, 95 %CI: 0.33 âˆ¼ 1.68), or without underlying diseases (B = -1.67, 95 %CI:-2.42 âˆ¼ -0.92) were also related with prevention practices. In general, this survey indicated that the stroke-related knowledge and prevention practices of participants were not good enough. Stroke related knowledge, age, sex, physical activity, and underlying disease were significant factors related to stroke prevention practices. These findings suggest the need to focus on stroke health education for stroke patients.

5.
Neurosci Lett ; 796: 137052, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36608927

ABSTRACT

OBJECTIVE: In this study, we aimed to investigate the relationships among plasma p-tau181, APOE ε4, and cognitive performance in non-demented elderly individuals. METHODS: We used individuals (n = 630) with cognitive normal (CN, n = 182) and mild cognitive impairment (MCI, n = 448). Multiple linear regression models were performed to test the effects of APOE ε4 × plasma p-tau181 interaction on MMSE, CDR-SOB, ADAS-cog13, and RAVLT immediate recall. All models adjusted for age, sex, and education. RESULTS: In total, our study comprised 630 samples including 364 APOE ε4 non-carriers and 266 APOE ε4 carriers. In APOE ε4 carriers, plasma p-tau181 was significantly associated with MMSE (B = -0.04, p = 0.003), ADAS-Cog13 (B [unstandardized coefficient] = 0.21, p < 0.001), CDR-SB (B = 0.02, p = 0.003) and RAVLT immediate recall ((B = -0.17, p = 0.035). After correcting for Aß status and diagnosis, the interaction between APOE ε4 and plasma p-tau181 was significant or marginally significant associations for RAVLT immediate recall (p = 0.076), MMSE (p = 0.011), CDR (p = 0.008), and ADAS-Cog13 (p < 0.001). CONCLUSIONS: Our findings suggested that plasma p-tau181 levels predicted cognitive performance among non-demented older adults, but only in the APOE ε4 carriers.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Apolipoprotein E4/genetics , Cognition , Cognitive Dysfunction/genetics , Linear Models , Heterozygote , Neuropsychological Tests , Alzheimer Disease/psychology
6.
Neurologist ; 28(5): 277-280, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-36715665

ABSTRACT

OBJECTIVES: Interleukins (ILs) play several critical roles in modulating the occurrence and development of atherosclerosis-related diseases. We aimed to investigate the associations between ILs and the diagnosis, progress, and functional outcome in patients with large-artery atherosclerotic (LAA) stroke. METHODS: Plasma levels of IL-2, IL-4, IL-6, and IL-10 were measured within 24 hours after stroke in 181 patients with first-time LAA stroke and on admission in 181 age-matched and sex-matched controls. NIHSS scores were recorded at admission and on Day 1, Day 2, Day 3, Day 4, and Day 5 after the stroke. Functional outcome was measured by the modified Rankin Scale at 3 months after stroke. Subgroup analyses were compared based on short-term progress within 5 days (ΔNIHSS ≥3) and 3-month unfavorable outcome (modified Rankin Scale >2). Logistic regression analysis adjusted for relevant confounders was performed. RESULTS: IL-6 levels were higher in patients with LAA stroke than in controls [AOR (95% CI), 0.701 (95% CI 0.651-0.748, P <0.001], with an area under the receiver operating characteristic curve (AUC) of 0.701. Higher IL-6 levels were associated with short-term progression [AOR (95% CI), 1.070 (1.009, 1.135), P =0.025], with an AUC value of 0.720. Higher IL-6 levels were associated with unfavorable outcomes [AOR (95% CI), 1.075 (1.002, 1.153), P =0.040], with an AUC value of 0.658. No difference in IL-2, IL-4, or IL-10 was found between the groups. CONCLUSIONS: Plasma levels of IL-6 are higher in patients with LAA stroke and are independently associated with short-term progression and 3-month functional outcomes after stroke.


Subject(s)
Atherosclerosis , Stroke , Humans , Interleukin-6 , Interleukin-10 , Interleukin-2 , Interleukin-4 , Stroke/complications , Arteries
7.
Exp Neurol ; 359: 114271, 2023 01.
Article in English | MEDLINE | ID: mdl-36370840

ABSTRACT

Cholinergic system dysfunction has been considered as a critical feature of neurodegenerative progression in Alzheimer's disease (AD). The α7 nicotinic acetylcholine receptors (α7-nAChRs) are widely expressed in the hippocampus cortex and play an important role in memory formation, considered as potential therapeutic agents targets. However, underlying mechanisms have not been fully elucidated. Here, we combine behavioral, molecular biological methods with in vitro slice and in vivo multichannel electrophysiological recording techniques to investigate the molecular, cellular synaptic and neuronal mechanisms of activating α7-nAChR by PHA-543613 (a selective α7-nAChR agonist), which influences the impaired cognitive function using presenilin 1 (PS1) and presenilin 2 (PS2) conditional double knockout (cDKO) mice. Our results demonstrated that PHA-543613 treatment significantly improved the impaired hippocampus-related memory via recovering the reduced the hippocampal synaptic protein levels of α7-nAChR, NMADAR and AMPAR, thereby restoring the impaired post-tetanic potentiation (PTP), long-term potentiation (LTP), activation of molecular signaling pathway for neuronal protection, theta power and strength of theta-gamma phase-amplitude coupling (PAC) at hippocampus in 6-month-old cDKO mice. For the first time, we systematically reveal the mechanisms by which PHA-543613 improves memory deficits at different levels. Therefore, our findings may be significant for the development of therapeutic strategies for AD.


Subject(s)
Alzheimer Disease , alpha7 Nicotinic Acetylcholine Receptor , Mice , Animals , alpha7 Nicotinic Acetylcholine Receptor/agonists , Presenilin-1/genetics , Presenilin-1/metabolism , Presenilin-2/genetics , Presenilin-2/metabolism , Mice, Knockout , Memory Disorders/drug therapy , Memory Disorders/metabolism , Hippocampus/metabolism , Alzheimer Disease/metabolism
8.
Neurologist ; 28(3): 190-194, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36125978

ABSTRACT

INTRODUCTION: The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS. CASE REPORT: A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes. CONCLUSION: Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.


Subject(s)
Acidosis, Lactic , Diabetes Mellitus, Type 2 , MELAS Syndrome , Stroke , Female , Humans , Aged , MELAS Syndrome/diagnosis , MELAS Syndrome/genetics , Mutation/genetics , DNA, Mitochondrial/genetics , Cerebral Infarction
9.
Front Med (Lausanne) ; 9: 859682, 2022.
Article in English | MEDLINE | ID: mdl-36213663

ABSTRACT

Background: The safety of the COVID-19 vaccine in patients at stroke risk is poorly understood. Methods: A survey was conducted on risk factors related to stroke and adverse reactions to vaccines. The participants were divided into low-, medium-, and high-risk groups, according to the stroke risk scorecard recommended by the Stroke Prevention and Control Engineering Committee of the National Health and Family Planning Commission. Factors associated with adverse reactions were analyzed. Reasons for non-vaccination and the aggravation of underlying diseases after vaccination were investigated. Results: 1747 participants participated (138 unvaccinated) and 36.8, 22.1, 41.1% of the vaccinated participants had low, medium, high risk of stroke, respectively. The incidence of adverse reactions after the first and second injection was 16.6, 13.7%, respectively. There was no difference in the incidence of adverse reactions among different risk groups. Sex, vaccine type, sleep quality, worry of adverse reactions, age, and education level were significantly related to adverse reactions to vaccination. The most popular reason for non-vaccination for medium- or high risk-participants was the aggravation of the existing disease. Only 0.3% of vaccinated participants reported slight changes in blood pressure, sugar levels, and lipid levels. No aggravation of stroke sequelae, atrial fibrillation, or transient ischemic attack was reported. Conclusions: Vaccination against COVID-19 (inactive virus) is safe for people at risk of stroke when the existing disease condition is stable. It is suggested to strengthen vaccine knowledge and ensure good sleep before vaccination.

10.
JAMA Netw Open ; 5(5): e2210596, 2022 05 02.
Article in English | MEDLINE | ID: mdl-35522283

ABSTRACT

Importance: Promotion of clinician adherence to stroke guidelines can improve stroke outcomes. Objective: To investigate the outcomes of a multilevel system program on clinician adherence to guidelines for treatment of patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This quality improvement study used a prospective interrupted time series (ITS) and difference-in-difference (DID) design, from August 1, 2018, to January 31, 2020, divided into preprogram term and short and long postprogram terms; each term had 6 months. Data were collected during hospitalization and at discharge with an automated medical record data capture system in 58 public hospitals in Zhejiang province, China. Data were analyzed from August 2018 to January 2020. Exposures: The multilevel system program included a modularized standard template for medical records, centrally supported continuing education, continuous monitoring and feedback, and collaborative workshops. Main Outcomes and Measures: The primary outcome was adherence to 12 key performance indicators (KPIs), expressed as (1) percentage of patient-applicable KPIs achieved in each participant and (2) percentage of participants among whom all applicable KPIs were achieved (dichotomous all-or-none measure). The secondary outcome was severe disability or death (modified Rankin Scale 5-6) at discharge. Results: Among 45 091 patients (mean [SD] age, 69 [12] years; 18 347 female [40.7%]), 28 721 from 30 hospitals received the program and 16 370 from 28 hospitals continued routine care. In adjusted DID analysis, the program was associated with an increase in the absolute percentage of KPIs achieved per patient (6.46%; 95% CI, 5.49% to 7.43%), absolute rate of all-or-none success (8.29%; 95% CI, 6.99% to 9.60%), and decreased rate of severe disability or death at discharge (-1.68%; 95% CI, -2.99% to -0.38%). The ITS result showed the program was associated with an increase in KPIs achieved per patient per week (slope change in short-term period, 0.36%; 95% CI, 0.20% to 0.52%; level change in long-term period, (9.64%; 95% CI, 4.58% to 14.69%) and in all-or-none success (slope change in short-term period 0.34%; 95% CI, 0.23% to 0.46%; level change in long-term period 5.89%; 95% CI, 0.19% to 11.59%). Conclusions and Relevance: The centrally supported program was associated with increases in clinician adherence to guidelines and reduced the proportion of severely disabled or deceased patients with AIS at discharge, providing support for its wider implementation.


Subject(s)
Ischemic Stroke , Stroke , Aged , Female , Hospitals , Humans , Ischemic Stroke/therapy , Male , Prospective Studies , Quality Improvement , Stroke/therapy
11.
BMC Neurol ; 22(1): 13, 2022 Jan 07.
Article in English | MEDLINE | ID: mdl-34996385

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms. METHODS: 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed. RESULTS: Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. CONCLUSIONS: Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.


Subject(s)
Gastrointestinal Microbiome , Parkinson Disease , Cognition , Fatty Acids, Volatile , Humans , Parkinson Disease/drug therapy
12.
Neurosci Lett ; 756: 135955, 2021 06 21.
Article in English | MEDLINE | ID: mdl-33979700

ABSTRACT

We aimed to investigate whether obstructive sleep apnea (OSA) status affects the relationship between cognitive decline and age among non-demented elderly people. A total of 1422 participants (493 normal cognition and 929 amnestic mild cognitive impairment) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Based on the self-reported medical history of OSA, participants were categorized into two groups (OSA- and OSA +). Multiple linear regression models were performed to assess the effect of the OSA * Age interaction on MMSE, ADAS-cog11 and RAVLT immediate recall in non-demented group and in APOE ε4 carriers/non-carriers adjusting for gender and educational attainment. In the present study, the OSA + group demonstrated significant cognitive decline versus the OSA- group. In addition, in APOE ε4- group, our findings showed a significant OSA * age interaction for ADAS-cog11 and RVALT immediate recall, but not MMSE. No significant interaction was observed in the APOE ε4+ individuals. In conclusion, our findings implicate that OSA status may affect the association of age with cognitive impairment among non-demented older people.


Subject(s)
Aging/psychology , Cognition/physiology , Cognitive Dysfunction/complications , Sleep Apnea, Obstructive/complications , Aged , Aged, 80 and over , Apolipoprotein E4/genetics , Female , Genotype , Humans , Male , Neuropsychological Tests
13.
Front Cell Neurosci ; 15: 784154, 2021.
Article in English | MEDLINE | ID: mdl-34975411

ABSTRACT

Objective: The "Glymphatic" system, a network of perivascular tunnels wrapped by astrocyte endfeet, was reported to be closely associated with the diseases of the central nervous system. Here, we investigated the role of the glymphatic system in intracerebral hemorrhage (ICH) and its protective mechanism. Method: Experimental ICH model was induced by type IV collagenase in rats. Cerebral lymphatic blockage was induced by ligation and removal of cervical lymph nodes. The experimental rats were divided into sham-operated (SO) group, ICH group, and cerebral lymphatic blocking and ICH (ICH + CLB) group. Neurological scores were measured using the Garcia scoring system on the third and seventh day after ICH. Active caspase-3 was immunostained to evaluate neuronal apoptosis. Brain water content was calculated using the dry-wet specific gravity method. The expression of inflammatory factors TNF-α, IL-1ß, and IL-10 were detected using ELISA. Aquaporins-4 (AQP-4) and glial fibrillary acidic protein (GFAP) were detected using western blot analysis. Results: The neurological scores of rats in the CLB + ICH group were significantly lower than those in the in ICH group. The number of active caspase-3 neurons was significantly higher in the CLB + ICH group compared to the ICH group. CLB significantly aggravated ICH-induced brain edema 3 d after ICH. There was an increase in the expression of TNF-α, IL-1ß, IL-10, AQP-4, GFAP after ICH. The expression of TNF-α was significantly higher in the CLB + ICH group compared to ICH group 3 d after ICH while there was no difference 7 d after ICH. There was no statistical difference in the expression of IL-1ß between the ICH group and CLB + ICH group. However, the expression of IL-10 in the CLB + ICH group was significantly lower than that in the ICH group. Lastly, AQP-4 expression was significantly lower in the CLB + ICH group compared to the ICH group while the expression of GFAP was higher in the CLB + ICH group compared to the ICH group. Conclusion: CLB exacerbated cerebral edema, neuroinflammation, neuronal apoptosis and caused neurological deficits in rats with ICH via down-regulating AQP-4, up-regulating inflammatory TNF-α and inhibiting IL-10 expression. The glymphatic drainage system protects against neurologic injury after ICH induction in rats under normal physiological conditions.

14.
J Stroke Cerebrovasc Dis ; 29(1): 104483, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31727597

ABSTRACT

OBJECTIVE: Gastrodin, a glucoside of gastrodigenin, inhibits cerebral oxidant stress and apoptosis in multiple central nervous system injury, but its effect in intracerebral hemorrhage (ICH) remains unclear. This study investigated the effect of gastrodin on neuronal apoptosis and neurological deficits in rat ICH model. METHODS: In vitro experiments were performed using hematoma lysate-induced cell damage model in primary cortical neurons. Rat ICH model was produced by a caudatum injection of collagenase. Gastrodin was intraperitoneal injected after 2 hours following ICH. Cell viability, brain water content, neurological score, western blot, and immunofluorescence experiments were performed. RESULTS: Gastrodin significantly decreased hematoma lysate-induced reduction of cell viability and cell apoptosis in primary cortical neurons. Gastrodin significantly improved brain edema and neurological deficits post-ICH. Moreover, gastrodin administration significantly reduced levels of ROS, 8-OHDG, 3-Nitrotyrosine and MDA, while increased GSH-Px and SOD activity, and stimulated the upregulation of Keap1, Nrf2, and HO-1 signaling at 72 hours post-ICH. Furthermore, gastrodin significantly increased Bcl-2 expression, while reduced level of Bax, active caspase-3 and active caspase-9, also reduced the number of active caspase-3 or TUNEL positive neurons at 72 hours post-ICH. CONCLUSION: These results suggest that gastrodin is neuroprotective after ICH and the mechanism may be associated with the inhibition of oxidative stress and neuronal apoptosis.


Subject(s)
Apoptosis/drug effects , Benzyl Alcohols/pharmacology , Cerebral Cortex/drug effects , Cerebral Hemorrhage/drug therapy , Glucosides/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Animals , Apoptosis Regulatory Proteins/metabolism , Behavior, Animal/drug effects , Brain Edema/metabolism , Brain Edema/pathology , Brain Edema/prevention & control , Cells, Cultured , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/physiopathology , Disease Models, Animal , Male , Motor Activity/drug effects , Neurons/metabolism , Neurons/pathology , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Signal Transduction
16.
Sci Rep ; 8(1): 11729, 2018 08 06.
Article in English | MEDLINE | ID: mdl-30082879

ABSTRACT

Increasing evidence supports the involvement of periostin in the pathophysiological processes of stroke and atherosclerosis. The aim of this study was to assess circulating periostin levels at different times after large-artery atherosclerotic (LAA) stroke and their association with stroke. Serum periostin levels were measured using enzyme-linked immunosorbent assay on day 1 in 162 patients with LAA stroke and in 108 age- and sex-matched controls, on day 6 after stroke in 134 patients, and during the 4th week after stroke in 46 of the 162 patients. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS), and the stroke volume was measured. Outcome at 3 months was measured using the modified Rankin Scale (mRS). Our results indicated that periostin levels increased significantly on day 6 after stroke, and this increasing trend persisted for at least 4 weeks after the event. In addition, the increase in periostin levels was positively correlated with the NIHSS scores and stroke volume, but not with the mRS scores after adjusting for the NIHSS scores. In conclusion, these findings suggest that the increase in serum periostin levels observed after stroke may be associated with the stroke severity in patients with LAA stroke.


Subject(s)
Atherosclerosis/blood , Cell Adhesion Molecules/blood , Stroke/blood , Aged , Aged, 80 and over , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies
17.
Clin Chim Acta ; 478: 157-161, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29287901

ABSTRACT

BACKGROUND: Accumulating evidence has suggested that endocan and endoglin may play important roles in cardiovascular disease. However, no previous study has focused on these circulating levels in patients with large-artery atherosclerotic (LAA) stroke. METHODS: Serum levels of endocan and endoglin in 114 patients with LAA stroke and 114 age- and sex-matched controls were measured by ELISA. Serum samples from patients were available on day 1, day 6 and in the 4th week after ischaemic stroke(IS). Stroke severity was determined based on the NIHSS score and the stroke volume. An unfavourable outcome was defined as a mRS score>2 on day 90 after IS. RESULTS: The endocan levels were significantly higher in patients with LAA stroke compared with the controls (p=0.001), and after adjustment for other factors (p=0.001). In addition, higher endocan levels were independently associated with unfavourable outcomes on both day 1 and day 6 after IS (p=0.018 and p=0.011). Endoglin levels were decreased on day 6 (p=0.002) and then recovered in the 4th week after IS. No correlation was found between endocan or endoglin and stroke severity. CONCLUSIONS: Endocan levels are higher in patients with LAA stroke and can help in predicting the short-term unfavourable outcome. Endoglin levels are changed after stroke.


Subject(s)
Atherosclerosis/blood , Endoglin/blood , Neoplasm Proteins/blood , Proteoglycans/blood , Stroke/blood , Aged , Atherosclerosis/complications , Biomarkers/blood , Cardiovascular Diseases/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Stroke/etiology
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(6): 336-9, 2007 Jun.
Article in Chinese | MEDLINE | ID: mdl-17577437

ABSTRACT

OBJECTIVE: To investigate the expression and significance of matrix metalloproteinase-2 (MMP-2) and MMP-9 in peri-hematoma brain tissues after acute brain hemorrhage in human. METHODS: Forty-two patients with acute brain hemorrhage received surgery, the brain tissues adjacent to hemorrhagic site were obtained during surgery, and positive expressions of MMP-2 and MMP-9 were determined with immunohistochemical staining. Brain tissues from 30 patients with cerebral trauma were obtained to serve as controls. RESULTS: The positive expressions of MMP-2 and MMP-9 in focal brain tissues were significantly elevated in early acute brain hemorrhage. Compared with 28 and 27 cases with MMP-2 and MMP-9 positive expression respectively in control group, there were 39 and 37 cases with MMP-2 and MMP-9 positive expression respectively in acute brain hemorrhage group. There were no significant differences between two groups (both P>0.05). CONCLUSION: MMP-2 and MMP-9 might contribute to brain edema formation in the acute intra-cerebral hemorrhage of human.


Subject(s)
Brain/enzymology , Cerebral Hemorrhage/enzymology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Adult , Aged , Female , Humans , Male , Middle Aged
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