Juexian Song

MiRNA-424 Protects Against Permanent Focal Cerebral Ischemia Injury in Mice Involving Suppressing Microglia Activation

Background and Purpose— We observed that microRNA-424 (miR-424) significantly decreased in an miRNA profile of circulating lymphocytes of patients with ischemic stroke. The present study focused on the potential and mechanism of miR-424 in protecting ischemic brain injury in mice. Methods— Cerebral ischemia was induced by middle cerebral artery occlusion in C57/BL6 mice. Cerebral infarction volume, neuronal apoptosis, and microglia activation were determined by 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence, and Western blot. BV2 microglial cell activity, cell cycle, mRNA, and protein levels of miR-424 targets were accessed by enzyme-linked immunosorbent assay, flow cytometry, real-time polymerase chain reaction, and Western blot, respectively. Results— MiR-424 levels were decreased in the plasma of patients with acute ischemic stroke, as well as in mouse plasma and ipsilateral brain tissue at 4, 8, and 24 hours after ischemia, likewise, in the cortex, hippocampus, and basal ganglia, respectively, after 8-hour ischemia. Interestingly, pre- and post-treatment with overexpression of miR-424 both decreased cerebral infarction size and brain edema after middle cerebral artery occlusion. Meanwhile, lentiviral overexpression of miR-424 inhibited neuronal apoptosis and microglia activation, including suppressing ionized calcium binding adaptor molecule-1 immunoreactivity and protein level, and reduced tumor necrosis factor-&agr; production. In vitro study demonstrated that miR-424 mimics caused G1 phase cell-cycle arrest, inhibited BV2 microglia activity, and reduced the mRNA and protein levels of CDC25A, cyclin D1, and CDK6 in BV2 microglial cells, which were upregulated in brain of middle cerebral artery occlusion mice. Conclusions— MiR-424 overexpression lessened the ischemic brain injury through suppressing microglia activation by translational depression of key activators of G1/S transition, suggesting a novel miR-based intervention strategy for stroke.

Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia.

Abstract Objectives: This study examines the efficacy of puerarin, a drug used in traditional Chinese medicine, in attenuating ischemic brain injury after cerebral ischemia and reperfusion, and explores possible mechanisms underlying neuroprotective effects. Methods: The animal model of ischemia/reperfusion injury was induced by middle cerebral artery occlusion for 2 hours followed by up to 72 hour reperfusion. The rats were randomly assigned into four groups (n=6/group): puerarin at 100, 200 and 400 mg/kg or saline, administered intraperitoneally. Neurological outcome and infarct volume by 2% triphenyl tetrazolium chloride staining were determined 72 hours after reperfusion. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining was used to detect the cell damage of brains (n=5/group). Erythropoietin activation was detected by enzyme-linked immunosorbent assay (n=5/group). Results: Compared with the vehicle saline group, puerarin decreased infarction volume at doses of 200 mg/kg (p=0.045) and 400 mg/kg (p=0.0002), but not at 100 mg/kg (p=0.387). Functional neurological outcome was improved with puerarin at 400 mg/kg (p=0.015), but not at 100 mg/kg (p=0.68) or 200 mg/kg (p=0.056). Puerarin significantly decreased the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining cells compared with the vehicle group 4, 24 and 72 hours after reperfusion. The erythropoietin activity was higher in puerarin treated group compared with the vehicle group. Discussion: Puerarin has neuroprotection effects in rats at doses of 200 and 400 mg/kg, administered intraperitoneally after transient middle cerebral artery occlusion which may be partly due to activation of erythropoietin activity.

Improvement of hematoma absorption and neurological function in patients with acute intracerebral hemorrhage treated with Xueshuantong

Spontaneous intracerebral hemorrhage (ICH) leads to high mortality and morbidity. Currently, there is no effective therapy for ICH. Herein we conducted a clinical study in patients with acute ICH to investigate the efficacy of Xueshuantong Injection, a Chinese herbal prescription known for treatment of ischemic diseases in China. Patients (n=63) were randomly assigned to control (n=29) and Xueshuantong Injection treatment (175 mg/d, n=34) groups. Both groups were evaluated using their history and vital signs. The National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume by CT scanning, and inflammatory factors were assessed before and after two weeks treatment. There were no significant differences in all parameters between two groups before treatment. The treatment group showed significant decreases in both NIHSS score and hematoma volume, compared to control group after treatment (P<0.01 and P<0.05, respectively). Furthermore, the inflammatory factors, as measured by leukocytes, neutrophil percentage and C-reactive protein values, were significantly reduced in treatment group compared to control group after treatment (P<0.05, P<0.05, P<0.01 respectively). Our results showed that treatment with Xueshuantong Injection reduced inflammatory response and increased hematoma absorption, which significantly improved recovery of neurological function. This suggests Xueshuantong Injection as a potential treatment of patients with acute ICH.

Study on the Correlation of Tongue Manifestation with Fibrinogen and Neutrophil in Acute Cerebral Infarction Patients

ObjectiveTo investigate the correlation of tongue manifestation with the fibrinogen level and the neutrophil count in blood of acute cerebral infarction patients.MethodsA total of 200 patients with first unilateral cerebral infarction in Neurology Department of Xuanwu Hospital from March, 2008 to February, 2009 were recruited in this study. The correlation of the tongue fur color and texture with the blood fibrinogen level and the neutrophil count was analyzed in these patients.ResultsThe level of fibrinogen and neutrophil count in thick fur group were significantly higher than that in thin fur group (P<0.05). There was no statistical difference in the level of fibrinogen and neutrophil count found between moist fur and dry fur. Statistical significance existed in the level of fibrinogen between the greasy tongue fur group and non-greasy tongue fur group (P<0.05). The level of fibrinogen and the neutrophil count were compared among different fur color groups, revealing that the level of fibrinogen in yellowish fur group was higher than that of white fur group and normal value with statistical significance (P<0.05) with neutrophil count in yellowish fur group being significantly higher than that in white fur group.ConclusionOur results suggested that the change of tongue manifestation was associated with the level of fibrinogen and the neutrophil count in the blood of cerebral infarction patients.

A pilot study on the relationship between tongue manifestation and the degree of neurological impairment in patients with acute cerebral infarction

ObjectiveTo discuss the relationship between tongue manifestation and the degree of neurological impairment in the patients with acute cerebral infarction.MethodsTwo hundred patients with first unilateral cerebral infarction were recruited. The relationship between different tongue manifestation and National Institute of Health Stroke Scale (NIHSS) were analyzed.ResultsNIHSS scores in the patients from different tongue color groups were analyzed and further analysis demonstrated that the NIHSS score was higher in the patients with red or bluish-purple tongue than that of those with the pink (P <0.01). On tongue fur, the NIHSS score in the patients with thick fur was higher than that of those with the thin (P=0.003). NIHSS score in patients with slippery, moist or dry fur was significant different (P=0.003), Further analysis demonstrated that the NIHSS score was higher in the patients with dry fur than that of those with moist fur, and had statistical significance (P=0.01). The NIHSS score was higher in patients from greasy fur group than that of the non-greasy (P=0.002). There was significant difference of NHISS score in the patients with different fur color (P=0.000), and further analysis demonstrated that the NHISS score in white-yellow, yellow fur group were higher than that of the white (P=0.06 or 0.000).ConclusionThe changes of tongue manifestation might be associated with the degree of neurological impairment in the patients with acute cerebral infarction.

A pilot study on the correlation of tongue manifestation with the site of cerebral infarction in patients with stroke.

ObjectiveTo discuss the correlation of tongue manifestation with the site of cerebral infarction in patients with acute cerebral infarction.MethodsFrom March 2008 to February 2009, 200 cases of hospitalized patients with first unilateral cerebral infarction were chosen in the Department of Neurology, Xuanwu Hospital. The correlation of different tongue color, fur texture, fur color with the site of cerebral infarction was analyzed.ResultsThe site of cerebral infarction in patients were compared between different tongue color by Chisquare test (P=0.314), and further correspondence analysis demonstrated that there was correlation between red tongue and cortical-subcortical infarction group. The site of cerebral infarction in patients were compared between thick fur group and thin fur group, cortical-subcortical infarction occurred more frequently in the former (P=0.0008). The site of cerebral infarction in patients were compared between dry fur group, moist fur group and smooth fur group, correspondence analysis demonstrated there was correlation between dry fur and cortical-subcortical group. The site of cerebral infarction in the patients were compared between white fur group, white-yellow fur group and yellow fur group (P=0.010), and correspondence analysis demonstrated there was correlation between white fur and brainstem infarction; white-yellow fur has relationship with cortical infarction; subcortical infarction was weakly related with white-yellow fur; there was closer relationship between yellow fur and cortical-subcortical infarction.ConclusionThe change of tongue manifestation was associated with the site of cerebral infarction in patients, providing a new combining site for diagnosing cerebrovascular diseases by integrative medicine.

Treatment of Naoxueshu Promotes Improvement of Hematoma Absorption and Neurological Function in Patients with Acute Intracerebral Hemorrhage

Aims: To evaluate the clinical efficacy of Naoxueshu oral liquid in the treatment of intracerebral hemorrhage (ICH) patients. Methods: In our study, December 2008 to August 2010, 88 patients with intracerebral hemorrhage were enrolled and 87 patients with complete information of whom 44 patients received Naoxueshu oral liquid plus regular treatment (Naoxueshu group), 43 patients received regular treatment (control group) only. Naoxueshu oral liquid 10 ml was taken in the Naoxueshu group, with 3 times a day for 21 consecutive days. The regular treatment included (1) dehydration treatment by 20% mannitol; (2) therapy to deal with complications including; (3) supportive therapy. The general clinical information, neurological assessment information, laboratory information, and the hematoma volume information were collected and analyzed pre-and post-treatment. Results: We did not find differences in the information between two groups before treatment (p > 0.05). 21-day after treatment, the white blood cell (WBC) count, hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), Barthel index (BI), and traditional Chinese medicine (TCM) syndrome score in the Naoxueshu group and control group were significantly decreased than before (pnaoxueshu < 0.01, pcontrol < 0.05), and the changes of the WBC count, hematoma volume, NIHSS score, mRS score, and TCM syndrome score in Naoxueshu group were greater than that of control group (P < 0.001). Conclusion: Naoxueshu oral liquid plus regular treatment could decrease the inflammatory response and hematoma, and improve outcomes of ICH patients than regular treatment only. This suggests that Maixueshu oral liquid is a potential treatment for ICH patients.

Treatment of Human Urinary Kallidinogenase Combined with Maixuekang Capsule Promotes Good Functional Outcome in Ischemic Stroke

Aims: To evaluate the clinical efficacy of Human Urinary Kallidinogenase (HUK) and Maixuekang capsule in the treatment of acute ischemic stroke (AIS) patients. Methods: In this study, from January 2016 to July 2016, 60 patients with acute ischemic stroke were enrolled and 56 patients with complete information of whom 21 patients received HUK+ basic treatment (HUK group), 16 patients received HUK+ Maixuekang capsule + basic treatment (HUK+ Maixuekang group), 19 patients received basic treatment (control group). 0.15 PNA unit of HUK injection plus 100 ml saline in intravenous infusion was performed in the HUK group and HUK+ Maixuekang group, with once a day for 14 consecutive days. 0.75 g Maixuekang capsules were taken in HUK+ Maixuekang group, with three times a day for 14 consecutive days. The National Institutes of Health Stroke Scale (NIHSS) scores in three groups were analyzed 7 days after treatment. The modified Rankin Scale (mRS) scores in three groups were analyzed 12 month after the treatment. Results: No difference was found in the NIHSS scores, age, gender, and comorbidities between three groups before treatment (p > 0.05). Seven days after treatment, the NIHSS scores in the HUK group and HUK+ Maixuekang group were significantly decreased than before (p HUK = 0.001, p HUK+Maixuekang < 0.001), and lower than that in the control group (p HUK = 0.032; p HUK+Maixuekang < 0.001). Twelve months after treatment, good functional outcome rate (12 month mRS score ≤ 2) in the HUK group and HUK+ Maixuekang group was significantly higher than that in the control group (p HUK = 0.049, p HUK+Maixuekang = 0.032). Conclusion: The treatment of HUK or HUK combined with Maixuekang capsule can effectively improve the neurological function and promote long-term recovery for AIS patients.

Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats.

Luoyutong (LYT) capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose) as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

Correlation between tongue manifestations and glucose, total cholesterol, and high-density lipoprotein cholesterol in patients with acute cerebral infarction

OBJECTIVE To analyze the association between tongue manifestations and the levels of glucose (GLU), total cholesterol (TCH), and high-density lipoprotein cholesterol (HDL-C) in subjects with acute cerebral infarction. METHODS Hospitalized patients with first unilateral cerebral infarction in the Neurological Department of Xuanwu Hospital were included and the correlation between tongue fur color, fur nature, and the levels of GLU, TCH, HDL-C were analyzed. RESULTS HDL level in the thin fur group was higher than that in the thick fur group (P = 0.02). The difference in the levels of GLU, TCH, and HDL-C among the groups was significant (P < 0.05), classified in terms of slippery, moist, and dry fur. Further comparison between the groups by Student-Newman-Keuls test showed that GLU level in the dry fur group was the highest. Moreover, the TCH level in the slippery fur group was higher than the other two groups. CONCLUSION A correlation between tongue manifestations and GLU, TCH, HDL-C was identified in the patients with acute cerebral infarction.