1.Endothelial glycocalyx: a potential therapeutic target for cerebrovascular diseases
Yisong LI ; Juan ZHU ; Mingjia YU ; Jiawei XU ; Kaibin HUANG ; Suyue PAN
International Journal of Cerebrovascular Diseases 2024;32(3):191-196
Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.
2.Protective effect of Huatuo Zaizao pills on white matter injury and cognitive impairment in mice with chronic cerebral hypoperfusion
Hua LI ; Zhentong LI ; Jiancong CHEN ; Kaibin HUANG ; Suyue PAN
International Journal of Cerebrovascular Diseases 2024;32(7):512-520
Objective:To investigate the protective effect and related mechanisms of Huatuo Zaizao pills (HT) on white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in mice. Methods:Forty adult male C57BL/6J mice were randomly divided into sham-operation group, bilateral carotid artery stenosis (BCAS) model group, and HT group. An animal model of BCAS was constructed using the spring loop into the bilateral common carotid arteries. After continuous treatment with 5 g/kg HT (or an equal amount of purified water) for 4 weeks, cognitive function was evaluated using the novel object recognition test. Morphological and structural changes in myelin sheath were evaluated by LFB myelin staining. White matter damage and glial cell expression were detected by myelin associated glycoprotein (MAG) in the corpus callosum, ionized calcium-binding adapter molecule 1 (IBA-1), and glial fibrillar acidic protein (GFAP) in corpus callosum and hippocampus through immunofluorescence staining. Real time quantitative polymerase chain reaction (qPCR) was used to detect mRNA expressions of myelin-associated proteins, Janus kinase 2 (JAK2), signal transducer and activator of the transcription 3 (STAT3) in corpus callosum, as well as brain-derived neurotrophic factor (BDNF), glutathione peroxidase 1 (GPx-1), and various inflammatory factors in hippocampus.Results:The novel object recognition test showed that mice had significant working memory impairment at 4 weeks after BCAS ( P<0.01), while the HT group showed significant improvement in working memory impairment compared to the BCAS group ( P<0.01). LFB myelin staining showed significant myelin damage in the BCAS group ( P<0.001), while the degree of myelin damage in the HT group was significantly improved compared to the BCAS group. Immunofluorescence staining showed that both the BCAS and HT groups had proliferation of microglia in the corpus callosum and hippocampus, and there was no significant difference between the two groups. In contrast, the activation of astrocytes in the corpus callosum was significantly improved in the HT group compared to the BCAS group ( P<0.05). qPCR showed upregulation of myelin-associated proteins as well as JAK2 and STAT3 mRNA expression in the BCAS group. Compared with the BCAS group, the expressions of JAK2 and STAT3 mRNA were decreased in the HT group (all P<0.05), while the expression of myelin-associated proteins were upregulated (all P<0.05). There were no significant difference in the expressions of inflammatory factors, BDNF, and GPX1 mRNA in the hippocampal tissue between the BCAS group and the HT group. Conclusion:HT may improve cognitive impairment and white matter damage in mice with chronic cerebral hypoperfusion, and the JAK2-STAT3 pathway may be one of its effect pathways.
3.Clinical characteristics of 30 patients with intracranial hypotension syndrome
Siqi WENG ; Yanan CAI ; Sichen HE ; Guohui HUANG ; Zihui DENG ; Bin CHEN ; Xiaojun LIU ; Suyue PAN ; Yabin JI
Chinese Journal of Nervous and Mental Diseases 2024;50(5):263-267
Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.
4.Predictors and predictive scales of malignant brain edema in patients with acute ischemic stroke
Linhan WANG ; Xiaolin ZHAO ; Jiawei XU ; Kaibin HUANG ; Suyue PAN
International Journal of Cerebrovascular Diseases 2022;30(9):684-688
Malignant cerebral edema (MCE) can lead to deterioration of neurological function in patients with acute ischemic stroke, and significantly increase the mortality and disability rate. Therefore, early detection and intervention of MCE is crucial for saving patients' lives. This article reviews the predictors and preventive scales of MCE after acute ischemic stroke.
5.Predictive factors for futile recanalization of acute anterior circulation ischemic stroke after endovascular treatment
Wei LI ; Kaibin HUANG ; Yongming WU ; Suyue PAN
International Journal of Cerebrovascular Diseases 2021;29(3):201-205
Although endovascular therapy improves the recanalization rate of acute large vessel occlusive ischemic stroke, about half of the patients still have poor functional outcome at 90 d, which is called " futile recanalization" . This article reviews and summarizes the predictive factors of futile recanalization after endovascular therapy in acute anterior circulation ischemic stroke, in order to provide help for clinical work and scientific research in the future.
6.Mismatch of ASPECTS based on arterial spin labeling and diffusion-weighted imaging as an indicator for mechanical thrombectomy in patients with wake-up stroke
Dongmei WANG ; Peng HAO ; Mengyao WANG ; Zhenzhou LIN ; Liang ZHOU ; Zusen FAN ; Yue PAN ; Xiaomei ZHANG ; Suyue PAN ; Zhong JI
Journal of Southern Medical University 2020;40(1):1-5
Objective To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans. Methods Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch. Results The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7%) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge. A mRS score of≤2 at 90 days was achieved in 8 of the 12 patients (66.7%). Conclusion The mismatch between ASPECTS assessed based on ASL and DWI can detect a true mismatch in patients with acute LVO of the anterior circulation, and can be used for rapid screening of patients eligible for thrombectomy.
7.Mismatch of ASPECTS based on arterial spin labeling and diffusion-weighted imaging as an indicator for mechanical thrombectomy in patients with wake-up stroke
Dongmei WANG ; Peng HAO ; Mengyao WANG ; Zhenzhou LIN ; Liang ZHOU ; Zusen FAN ; Yue PAN ; Xiaomei ZHANG ; Suyue PAN ; Zhong JI
Journal of Southern Medical University 2020;40(1):1-5
Objective To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans. Methods Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch. Results The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7%) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge. A mRS score of≤2 at 90 days was achieved in 8 of the 12 patients (66.7%). Conclusion The mismatch between ASPECTS assessed based on ASL and DWI can detect a true mismatch in patients with acute LVO of the anterior circulation, and can be used for rapid screening of patients eligible for thrombectomy.
8.Glibenclamide protects neurovascular units in rats with cerebral ischemia/reperfusion injury by regulating inflammatory signaling pathway HSP70/p-Akt/MMP-9/COX-2
Chinese Journal of Neuromedicine 2019;18(8):767-778
Objective To investigate the protective effect of glibenclamide on neurovascular units (NVUs) and its possible mechanism in cerebral ischemia/reperfusion injury models.Methods One hundred and twenty healthy male SD rats were randomly divided into sham-operated group, model group, and glibenclamide (GBC) treatment group (n=40). Two h reperfusion models of acute focal middle cerebral artery occlusion were prepared by thread occlusion in rats of the latter two groups; rats in the model group were treated with 0.05% DMSO saline solution two h after ischemia, and rats in the GBC treatment group were given intraperitoneal injection of 10μg/kg GBC with single dose. Immunofluorescence and Western blotting were used to detect the protein levels of sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4) 8 h after reperfusion, and ELISA was used to detect the plasma level of matrix metalloproteinase 9 (MMP-9). At 24 h after reperfusion, Zea Longa scale was used to determine the neurological deficits; water content in the brain tissues was detected by dry and wet weight method, and blood-brain barrier (BBB) permeability was detected by Evans blue (EB) staining; Nissl staining was employed to detect the survival neurons; ionized calcium bindingadaptor molecule-1 (Iba-1) and cyclooxygenase-2 (COX-2) positive cells and IgG seepage quantity were detected by immumohistochemical staining to assess the neuro-vascular inflammation; the expressions of heat shock protein 70 (HSP70), phosphorylated protein kinase B (p-Akt), phosphorylated c-jun amino-terminal kinase (p-JNK), and phosphatidylinositol-3 kinase (PI3K) were detected by Western blotting.Results (1) At 8 h after reperfusion, the protein expressions of SUR1 and TRPM4 in the brain tissues of the model group were significantly increased as compared with those of the sham-operated group (P<0.05), and the two proteins were co-located; as compared with those in the model group, the protein expressions of SUR1 and TRPM4 in GBC treatment group was decreased, but the differences were not statistically significant (P>0.05). As compared with the sham-operated group, the model group had significantly higher MMP-9 level (P<0.05); as compared with the model group, the GBC treatment group had significantly lower MMP-9 level (P<0.05). (2) At 24 h after reperfusion, as compared with the sham-operated group, the model group had significantly increased Zea Longa scale scores, statistically increased brain water content, significantly increased EB permeability, significantly increased IgG seepage quantity, significantly smaller number of Nissl's staining-positive neurons, significantly larger number of Iba-1, COX-2 positive cells, and significantly decreased protein expressions of HSP70 and p-Akt (P<0.05); as compared with the model group, the GBC treatment group had significantly decreased Zea Longa scores, statistically decreased brain water content, significantly decreased EB permeability, significantly decreased IgG seepage quantity, significantly larger number of Nissl's staining-positive neurons, significantly smaller number of Iba-1, COX-2 positive cells, and significantly increased protein expressions of HSP70 and p-Akt (P<0.05).Conclusion SUR1-TRPM4 expression is increased after cerebral ischemia/reperfusion injury, and inhibition of SUR1-TRPM4 with GBC shows a protective role in NVUs after cerebral ischemia/reperfusion injury, possibly by regulating HSP70/p-Akt/MMP-9/COX-2 inflammatory signal pathway.
9.Developing turns-amplitude clouds for healthy Chinese: reference values and influence factors
Yu PENG ; Shimeng ZHANG ; Minyi WU ; Yao WANG ; Suyue PAN
Chinese Journal of Neurology 2018;51(10):824-830
Objective To establish the reference values and evaluate influence factors of turns-amplitude clouds for healthy Chinese.Methods We recruited 59 healthy subjects From July 2017 to December 2017 in Nanfang Hospital,Southern Medical University,including 34 males and 25 females,who were divided into young group (15-39 years old),middle-aged group (40-64 years old) and the elderly group (over 65 years),respectively.The number of turns (NT) and mean amplitude (MA) normative data of sternocleidomastoid muscle,deltoid muscle,biceps brachii muscle,extensor digitorum muscle,abductor digiti minimi muscle,quadriceps femoris muscle,tibialis anterior muscle,and gastrocnemius muscle were obtained by using concentric needle electrodes.A total of 20-30 records were collected from each muscle in different degree of contraction.A linear regression of lg(MA-100) versus lgNT was made and the slope,intercept,the 95% confidence interval of intercept,the largest MA and largest NT were calculated for each muscle.The influence factors,such as gender,age,muscles,and dominant limbs on the shape of cloud were evaluated by using the Chow breakpoint test.Results Normal turns-amplitude clouds were obtained and presented in this article.Muscle and age were found to be the main influence factors affecting the shape of cloud,and gender may affect some clouds,while the dominant limbs had little influence on the shape of the cloud.Conclusion The reference values of turns-amplitude cloud based on muscle,gender and age are of practical significance in clinic.
10.Research progress of gut microbiota and microbiota-targeted therapy in critical ill patients
Ruoting XU ; Chuhong TAN ; Jia YIN ; Suyue PAN
Chinese Critical Care Medicine 2018;30(11):1099-1102
In physiological conditions, a diverse microbiota might enhance host defense. However, the gut microbiota of critically ill patients is characterized by lower diversity, lower abundances of key commensal genera, and overgrowth by one bacterial generation, a state known as dysbiosis. Increasing evidences indicate that microbiota-derived components can reach the systemic circulation from the gut and modulate immune homeostasis. Dysbiosis could have greater consequences for the critically ill patients and might contribute to poor outcome. In this review, we highlighted the crucial role of intestinal microbiota in systemic homeostasis in the critically ill patients and summarized emerging evidence in the field of microbiota-targeted therapies. This would provide new perspective for further establishing the causes and consequences of dysbiosis found in the critically ill patients as well as developing new strategies of intervention.

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