benzofurans and Cerebral-Infarction

Cerebral ischemia is also known as ischemic stroke. In recent years, research on neuroprotection after ischemia has became a hot spot as stroke can result in symptoms of nerve damages such as hemiplegia, learning and memory disorders. The key factors that cause the death of cells include excitotoxicity, oxidative damage, nitrosative stress and inflammation. However, there is no effective preparation for the treatment of post-ischemic nerve defects at present, so it is urgent to find and develop effective drugs for the treatment of nerve damages after ischemia. Traditional Chinese medicine has advantages and potentials in the treatment of neurological diseases. Many scholars have carried out related researches on the active ingredients of traditional Chinese medicine and achieved some good results. In this context, the researches on the neuroprotective effects of traditional Chinese medicines such as tetramethylpyrazine, butylphthalide and total saponins of Panax notoginseng were reviewed. The author found that the neuroprotective researches of traditional Chinese medicine mostly focused on anti-apoptosis, anti-inflammatory and anti-oxidative stress, but those effects were not sounique to the nervous system. Furthermore, most ingredients of traditional Chinese medicine showed a poor water-soluble property. In view of the research status and existing problems of traditional Chinese medicine in nerve injury, the suggestions for the research and development of the potent neuroprotective agents were proposed in this study from the perspective of pharmacological mechanism research and preparation theory.

Topics: Benzofurans; Brain Ischemia; Cerebral Infarction; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Neuroprotective Agents; Panax notoginseng; Pyrazines; Saponins

This study aims to explore the curative effect of dl-3-n-butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and hypersensitive C-reactive protein (hs-CRP) levels.. A total of 136 ACI patients treated in our hospital, who met the criteria, were selected and randomly divided into two groups: control group (n = 60, including 28 males and 32 females) and treatment group (n = 76, including 32 males and 44 females). Patients in the control group were treated with routine drug therapy, while patients in the treatment group were treated with NBP on this basis. A dose of 100 ml was administered by intravenous injection for 2 times/day, for 14 days. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and Barthel index (BI) self-care ability. The levels of the two factors in serum were measured using enzyme-linked immunosorbent assay, and the changes in levels of these two factors in serum at different time points before and after treatment were compared between the two groups.. (a) Lp-PLA2 and hs-CRP levels in the treatment group after treatment were significantly lower than those before treatment and those in the control group after treatment (p < .05). (b) The NIHSS and BI scores in the treatment group were significantly lower after treatment than before treatment and those in the control group after treatment (p < .05).. Dl-3-n-butylphthalide can improve the expression of Lp-PLA2 and hs-CRP in serum in ACI patients. Furthermore, NBP has significant efficacy in inhibiting inflammation and improving neurological symptoms.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Acute Disease; Benzofurans; C-Reactive Protein; Cerebral Infarction; Drug Monitoring; Female; Humans; Male; Middle Aged; Neuroprotective Agents; Treatment Outcome

Progressive cerebral infarction (PCI) is associated with high rates of mortality and disability. Many studies have shown that Dl-3n-butylphthalide (NBP) is effective against acute ischemic stroke. The administration of NBP can result in an increased number of capillaries in the ischemic region, promote the establishment of collateral circulation, protect the mitochondria, and narrow the infarction area, among other effects. In the present study, we evaluated the efficacy and safety of NBP for the treatment of PCI.Between March 2008 and May 2012, we performed a randomized, double-blind placebo-controlled study including 304 inpatients with PCI. These patients were randomly assigned to the test (152 cases) and control groups (152 cases). The test group received 200 mg of NBP soft capsules orally, 15 minutes before each meal, 3 times daily. The control group received 200 mg of placebo soft capsules orally, 15 minutes before each meal, 3 times daily. Treatment was administered during 21 days. The National Institute of Health Stroke Scale (NIHSS) score was assessed before the treatment and on days 7, 14, 21, and 30 after treatment. The Barthel index (BI) was assessed on the same days and on day 90.In the test group, the NIHSS scores on days 7, 14, 21, and 30 were 14.75 ± 4.85, 11.62 ± 3.49, 8.87 ± 5.17, and 6.38 ± 4.93, respectively. In the control group, they were 16.08 ± 3.76, 13.28 ± 5.02, 11.05 ± 4.25, and 8.43 ± 5.41 (P < .05), respectively. The BI on days 7, 14, 21, 30, and 90 were 51.57 ± 15.11, 61.21 ± 16.39, 70.48 ± 18.21, 76.41 ± 19.02, and 81.10 ± 15.52 for the test group and 46.79 ± 18.42, 55.93 ± 19.12, 64.84 ± 17.67, 70.65 ± 18.54, and 76.54 ± 17.05 for the control group (P < .05), respectively. Adverse events were elevation of alanine aminotransferase and aspartate aminotransferase (P > .05).NBP was useful to improve the outcome of patients with PCI and decreased their disability for activities of daily living. NBP was an efficacious and safe treatment for PCI.

Topics: Activities of Daily Living; Administration, Oral; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Benzofurans; Cerebral Infarction; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuroprotective Agents; Severity of Illness Index; Time Factors; Treatment Outcome

To observe the curative effect of dl-3-n-Butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on levels of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).. A total of 160 ACI patients treated in our hospital who met the criteria were selected and randomly divided into treatment group (n=80, including 42 males and 38 females) and control group (n=80, including 40 males and 40 females). The control group was treated with routine drug therapy, while the treatment group was treated with butylphthalide on this basis. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and the Activity of Daily Life Scale (ADL Scale). The levels of the two factors in serum were measured using enzyme-linked immunosorbent assay (ELISA), and the changes in the levels of the two factors in serum at different time points before and after treatment were compared between the two groups.. After treatment, the levels of the two factors in serum in both groups were significantly increased compared with those before treatment (p<0.05), and the increase in treatment group was more significant than that in control group (p<0.05). The scores of ADL scale in both groups were significantly increased after treatment compared with those before treatment, and the increase in treatment group was more significant than that in control group (p<0.05). The scores of NIHSS in both groups were significantly decreased compared with those before treatment, and the decrease in treatment group was more significant than that in control group (p<0.05).. NBP can improve the expressions of VEGF and bFGF in serum of ACI patients, and its effect is superior to that of conventional drugs.

Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Benzofurans; Cerebral Infarction; Female; Fibroblast Growth Factor 2; Humans; Male; Middle Aged; Neuroprotective Agents; Stroke; Vascular Endothelial Growth Factor A; Young Adult

To investigate the effect of Butylphthalide and Xue Shuan Tong on serum inflammatory factors and prognosis of patients with cerebral infarction. One hundred and twenty patients with acute cerebral infarction were randomly divided into control group, Butylphthalide group and Xue Shuan Tong group, with 40 patients in each group. Conventional therapy was performed in the control group; On the basis of conventional therapy, 100ml Butylphthalide intravenously twice a day was administrated among patients in Butylphthalide group; On the basis of conventional therapy, 250ml 0.9% NaCl intravenously once a day was conducted among patients in Xue Shuan Tong group. A treatment course of continuous 7 days was taken in the three groups. The serum levels of IL-2 and CGRP were detected for patients in the three groups before and after treatment. Carotid plaque thickness and size as well as intima-media thickness were detected by ultrasonic testing for patients in three groups before treatment and 90 days after follow-up. The NIHSS, Barthel and MRS scoring were performed for all the patients after 90-day follow-up to evaluate the prognosis. After treatment, differences in the levels of IL-2 and CGRP for patients in the three groups showed statistical significance (P<0.05), while the levels of IL-2 and CGRP in Xue Shuan Tong group were significantly higher than those in the other two groups (P<0.05). After 7-day treatment, plaque size and thickness in Xue Shuan Tong group and Butylphthalide group were significantly reduced, compared with those before treatment (P<0.05), but no significant differences was shown in the plaque size and thickness between Xue Shuan Tong group and Butylphthalide group (P>0.05) .The CA-IMT in Xue Shuan Tong group and Butylphthalide group was significantly reduced after treatment, and that in Butylphthalide group was significantly larger than that in Xue Shuan Tong group (P<0.05). After 90-day follow-up, NIHSS scores in Butylphthalide group were significantly less than those in the other two groups (P<0.05). After 90-day follow-up, Barthel scores in Butylphthalide group and Xue Shuan Tong group were significantly larger than those in control group (P<0.05), while differences between Butylphthalide group and Xue Shuan Tong group indicated no statistical significance (P>0.05). There were significant differences in MRS scores among patients in the three groups after 90-day follow-up (P<0.05). Butylphthalide and Xue Shuan Tong are clinically effective

Topics: Aged; Aged, 80 and over; Benzofurans; Calcitonin Gene-Related Peptide; Carotid Arteries; Carotid Intima-Media Thickness; Cerebral Infarction; Drugs, Chinese Herbal; Female; Humans; Inflammation; Interleukin-2; Male; Middle Aged; Nervous System Diseases; Plaque, Atherosclerotic; Prognosis

To explore the effects of butylphthalide on the levels of serum CRP, PAPK7, NT-3 and neurological function in patients with acute cerebral infarction (ACI). 120 patients with ACI who were treated at Peking University First Hospital from September 2014 to June 2016 were selected as the research objects. The patients were randomly divided into a control group and an observation group, with 60 cases in each group. Conventional methods were adopted in the control group, and the observation group used butylphthalide for treatment. Two months later, the clinical efficacy, serum C-reactive protein (CRP), Parkinson's disease protein 7 (PAPK7), neurotrophic factor-3 (NT-3) levels, and the National Institutes of Health Stroke Scale (NIHSS) score before and after treatment were put into comparison and analysis. Before treatment, the NIHSS score showed no significant difference between the two groups (p>0.05); An observably higher NIHSS score of the observation group compared with the control group was seen after treatment (p=0.000). Butylphthalide has a significant therapeutic effect on patients with ACI. It can effectively restore the patients' neurological function, and remarkably improve the serum CRP, PAPK7 and NT-3 levels, which is worthy of clinical promotion.

Topics: Aged; Benzofurans; C-Reactive Protein; Cerebral Infarction; Female; Gene Expression Regulation; Humans; Male; Neuroprotective Agents; Neurotrophin 3; Protein Deglycase DJ-1

To assess cerebral hemodynamic changes by transcranial doppler ultrasound in patients with acute cerebral infarction before and after treatment with butylphthalide, A total of 90 patients with acute cerebral infarction admitted to our hospital from January 2019 to January 2020 were selected and equally divided into the control group and the experimental group according to the order of admission. The control group was treated with conventional treatment, while the experimental group was additionally given butylphthalide drug treatment. The experimental group obtained better hemodynamic indexes as compared with the control group (P<0.05). The experimental group yielded a notably higher total clinical effective rate after treatment in contrast with the control group (P<0.05). After treatment, the serum indexes of the experimental group were evidently lower than those of the control group (P<0.05). After treatment, a remarkably lower NIHSS score of the experimental group than the control group was observed (P<0.05). The BI index score of the experimental group after treatment was considerably higher than that of the control group (P<0.05). After treatment, the MMSE score in the experimental group was significantly higher than it was in the control group (P<0.05). The treatment of butylphthalide in patients with acute cerebral infarction can effectively improve the clinical symptoms of the patients and the cerebral hemodynamics of the patients tested by TCD found that this treatment yields an excellent therapeutic effect and is worthy of promotion and application.

Topics: Acute Disease; Benzofurans; Brain Ischemia; Cerebral Infarction; Hemodynamics; Humans; Stroke; Ultrasonography, Doppler, Transcranial

To investigate the effect of tetramethylpyrazine hydrochloride combined with butylphthalide on serum S100B, CRP, Hcy and NIHSS score in patients with acute cerebral infarction. 80 patients with acute cerebral infarction treated in our hospital from February 2019 to February 2021 were selected for retrospective analysis, and according to different treatment methods, the patients were equally divided into control group (conventional treatment) and experimental group (tetramethylpyrazine hydrochloride and butylphthalide). After treatment, the total effective rate of patients in the experimental group was significantly higher than that in the control group (P<0.05); the levels of serum S100B, CRP and Hcy, and NHISS scores in the two groups decreased, and the experimental group was significantly lower than the control group (P<0.05); the ADL scores of the two groups increased and the experimental group witnessed higher score (P<0.05); the number of patients in the experimental group with scores of 0-2 and 5 were significantly larger than that in the control group (P<0.05). The combination of tetramethylpyrazine hydrochloride and butylphthalide emanates a promising result in the treatment of patients with ACI. It reduces serum S100B, CRP and Hcy levels, protects nerve tissue, and improves nerve function, and thus merits clinical application.

Topics: Acute Disease; Benzofurans; Brain Ischemia; Cerebral Infarction; Humans; Pyrazines; Retrospective Studies; S100 Calcium Binding Protein beta Subunit; Stroke

Topics: Adult; Aged; Benzofurans; Cerebral Infarction; Cytokines; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Kallikreins; Male; Middle Aged; Phosphopyruvate Hydratase; Treatment Outcome

This paper aimed to discuss the denoising ability of magnetic resonance imaging (MRI) images based on fuzzy C-means clustering (FCM) algorithm and the influence of Butylphthalide combined with Edaravone treatment on nerve function and vascular endothelial function in patients with acute cerebral infarction (ACI). Based on FCM algorithm, Markov Random Field (MRF) model algorithm was introduced to obtain a novel algorithm (NFCM), which was compared with FCM and MRF algorithm in terms of misclassification rate (MCR) and difference of Kappa index (KI). 90 patients with ACI diagnosed in hospital from December 2018 to December 2019 were selected as subjects, who were divided into combined treatment group (conventional treatment + Edaravone + Butylphthalide) and Edaravone group (conventional treatment + Edaravone) randomly, each consisting of 45 cases. The National Institutes of Health Stroke Scale (NIHSS) score and endothelial function index level such as plasma nitric oxide (NO), human endothelin-1 (ET-1), and vascular endothelial cell growth factor (VEGF) were compared before and after treatment between the two groups. The results showed that the MCR of NFCM was evidently inferior to FCM and MRF, and the KI was notably higher relative to the other two algorithms. After treatment, the NIHSS score of the combined treatment group was (9.09 ± 1.86) points and that of Edaravone group was (14.97 ± 3.44) points, with evident difference between the two groups (

Topics: Algorithms; Benzofurans; Biomarkers; Cerebral Infarction; Drug Therapy, Combination; Edaravone; Endothelium, Vascular; Female; Follow-Up Studies; Fuzzy Logic; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Neuroprotective Agents; Prognosis

Observe the clinical efficacy of l-3-n-Butylphthalide (NBP) in acute ischemic stroke (AIS) patients within 24 h after intravenous thrombolysis using recombinant tissue plasminogen activator (hereafter termed "IT").. One-hundred and seventy-eight patients with AIS were divided randomly into two groups: NBP and control. The former was given a NBP injection within 24 h after IT. After intravenous injection of NBP for 8-10 days, patients switched to soft capsules of NBP before or during meals. NBP treatment was continued for ≥30 days after hospital discharge. In the control group, NBP was not injected within 24 h after IT, and NBP capsules were not given after 8-10 days. Both groups were reviewed for CT or MRI 24 h after IT. The National Institutes of Health Stroke Scale (NIHSS) score was calculated. The number of patients with a modified Rankin scale (mRS) 0-2 before, 24 h, and 90 days after IT was documented. Prevalence of cerebral hemorrhage and reocclusion of blood vessels after IT was calculated.. There were no differences in sex, age, blood pressure, blood glucose, or cerebral-infarction types between the two groups before treatment. The NIHSS score 24 h after IT and the percentage of mRS scores 0-2 were not significantly different between the two groups. Compared with the control group, the NIHSS score in the NBP group was significantly improved at 90 days, and the number of patients with a mRS score 0-2 increased significantly. There was no significant difference in hemorrhage prevalence after IT between the two groups. Prevalence of blood-vessel occlusion after IT was significantly lower in the NBP group than that in the control group.. Use of NBP within 24 h after IT can reduce the prevalence of reocclusion of blood vessels without increasing the risk of cerebral hemorrhage.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Benzofurans; Capsules; Cerebral Infarction; Female; Humans; Male; Middle Aged; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator

Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory demyelinating disorders of the central nervous system; they are characterized by severe optic neuritis and transverse myelitis. Intravenous methylprednisolone pulse (IVMP) therapy is an effective treatment that is administered to patients in the acute phase of NMOSD; this therapy has achieved remarkable results in clinical practice. However, there are no reports on NMOSD patients who have experienced an acute bilateral cerebral infarction while undergoing IVMP treatment.. We report on a 62-yr-old woman who was undergoing IVMP therapy for the primary diagnosis of NMOSD. Unexpectedly, the patient's existing limb weakness worsened, and she developed motor aphasia on the second day of IVMP treatment. Additionally, brain magnetic resonance imaging revealed acute bilateral cerebral infarction.. The patient's clinical manifestations, medical imaging results, and laboratory test results were taken into consideration; the final diagnosis was acute bilateral cerebral infarction in the presence of NMOSD.. Subsequent to the onset of acute cerebral infarction, the patient was immediately treated with oral aspirin, atorvastatin, and intravenous butylphthalide. The hormone dose was adjusted to an oral 60-mg/d dose for maintenance; this was followed by immunoadsorption plasmapheresis for 3 days, and double-filtration plasmapheresis for 2 days.. Following treatment onset, the patient's ocular symptoms significantly improved, and her limb muscle strength gradually recovered. Two months after discharge, the patient's husband reported that she was able to walk with the help of others and take care of herself, and that there was no recurrence.. Medical professionals must be aware of the possibility of NMOSD patients with cerebrovascular risk factors suffering an acute cerebral infarction while undergoing high-dose IVMP therapy, as this therapy can exacerbate existing problems.

Topics: Acute Disease; Administration, Intravenous; Administration, Oral; Anticholesteremic Agents; Aphasia, Broca; Aspirin; Atorvastatin; Benzofurans; Cerebral Infarction; Female; Humans; Magnetic Resonance Imaging; Methylprednisolone; Middle Aged; Neuromyelitis Optica; Neuroprotective Agents; Plasmapheresis; Platelet Aggregation Inhibitors; Treatment Outcome

To study the effect of 3-n-butylphthalide (NBP) on neuronal apoptosis in rats with cerebral infarction (CI) through the p38/mitogen-activated protein kinase (MAPK) pathway.. A total of 30 rats were divided into control group (healthy rats, n=10), model group (CI rat model, n=10), and NBP group (CI rat model + intraperitoneal injection of NBP, n=10). Then, the neurological function, degree of cerebral ischemia, apoptosis of brain tissues, the protein and messenger ribonucleic acid (mRNA) expressions of p-p38 and MAPK in brain tissues were detected using the neurological score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and Western blotting, respectively.. In NBP group, the neurological score was significantly lower than in model group, and the difference was statistically significant (p<0.05). The results of TTC staining revealed that the area of the white region in brain slices was significantly larger in model group than in control group, indicating the successful establishment of middle cerebral artery occlusion (MCAO) model. Compared with model group, NBP group had a smaller area and lighter color of the white region in brain slices, suggesting that NBP markedly reduces the MCAO-induced CI. The apoptosis rate in NBP group was higher than in control group (p<0.05), but lower than in model group (p<0.05), while it was higher in model group than in control group (p<0.05). The protein expressions of p38 and MAPK in NBP group were higher than in control group (p<0.05), but lower than in model group (p<0.05), while they were higher in model group than in control group (p<0.05). Moreover, the mRNA expressions of p38 and MAPK were lower in control group than in model group (p<0.05), while they were higher in model group than in NBP group (p<0.05), but there was no significant difference in the mRNA expression of p38 between NBP group and control group (p>0.05).. NBP alleviates neuronal apoptosis in CI by down-regulating the p38 signal and inhibiting the expression of MAPK, thereby treating CI.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Benzofurans; Cerebral Infarction; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation; Injections, Intraperitoneal; MAP Kinase Signaling System; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Rats

The purpose of this study was to evaluate the cerebral protection of salvianolic acid B (Sal B) against cerebral I/R injury and investigate the underlying mechanism. As shown by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI) analyses, Sal B significantly reduced cerebral infarct size, and accompanied with improved neurobehavioral functions as indicated by the modified Bederson score and Longa five-point scale. Sal B decreased the production of reactive oxygen species (p < .05, n = 10). The data of Western blotting and reverse transcription quantitative real time polymerase chain reaction (qRT-PCR) analyses showed that the expression of GFAP, Iba1, IL-1β, IL-6, TNF-α and Cleaved-caspase 3 was significantly reduced by Sal B in I/R injured brain tissues as compared to corresponding controls (p < .05, n = 10). Over activation of astrocytes and microglia were inhibited by Sal B as shown by immunostaining of GFAP and Iba 1. These data suggest that Sal B has neural protective effects against I/R-induced cerebral injury and could be an effective candidate for further development of clinical therapy.

Topics: Animals; Benzofurans; Brain Injuries; Calcium-Binding Proteins; Caspase 3; Cerebral Infarction; Cytokines; Disease Models, Animal; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Neuroprotective Agents; Reperfusion

The aim of this study was to explore whether Dl-3-n-butylphthalide (DBT) could protect blood-brain barrier (BBB) of mice with experimental cerebral infarction and the relevant mechanism.. Adult male CD-1 mice were selected as the study objects. The permanent middle cerebral artery occlusion (MCAO) model was prepared by Longa's modified suture-occluded method. The mice were randomly divided into 3 groups: the sham operation group (Sham group), the cerebral infarction model group (CI group) and the DBT (120 mg/kg) intervention group (DBT group). Neurologic function deficits were evaluated by Longa's modified scoring method after 24 h of permanent MCAO. The wet and dry weight method was used for measuring water content in brain tissues. 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining method was applied to determine the volume of cerebral infarction. Changes in the protein and messenger ribonucleic acid (mRNA) expression levels of matrix metallopeptidase 9 (MMP-9), claudin-5, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), NF-E2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) in ischemic brain tissues were detected using immunohistochemistry, Western blotting and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Ultrastructure changes in BBBs were observed under an electron microscope.. DBT improved the neurologic function deficits of mice and reduced the infarction volume of mice with cerebral infarction. DBT alleviated edema and decreased the permeability of BBBs of mice with cerebral infarction. DBT down-regulated the expression of MMP-9 and up-regulated the expression of claudin-5 in brain tissues of mice with cerebral infarction. DBT increased the expressions of VEGF and GFAP. DBT improved the ultrastructure in capillary endothelial cells of BBBs and increased the expressions of Nrf-2 and HO-1.. DBT may protect BBB by activating the Nrf-2/HO-1 signaling pathway, thus achieving its protective effect on the brain.

Topics: Animals; Benzofurans; Blood-Brain Barrier; Brain; Cerebral Infarction; Heme Oxygenase-1; Male; Membrane Proteins; Mice; Neuroprotective Agents; NF-E2-Related Factor 2; Rats, Sprague-Dawley; Signal Transduction

This study investigates the impacts of n-butylphthalide (NBP) on the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) in rats with focal cerebral ischemia. The thread embolization method was used to prepare the rat model of cerebral ischemia-reperfusion (CIR). The animals were divided into a sham operation group, a model control group and NBP treatment group. The NBP group was orally administered 25 mg/kg NBP twice a day after the surgery. The immunohistochemistry and reverse transcription-polymerase chain reaction were performed to observe the protein and mRNA expressions of VEGF and TGF-β 16 hours, 1 day and 2 days after inducing CIR. The mRNA and protein expressions of VEGF and TGF-β1 in the model control group and the NBP treatment group were all increased after CIR, and those of the NBP treatment group at each post-CIR time point were higher than the model control group (p < 0.01). After CIR, the expressions of VEGF and TGF-β1 increased, suggesting that VEGF and TGF-β1 exhibited protective effects towards the ischemic brain injuries, and that NBP could upregulate the expressions of VEGF and TGF-β1 in the peri-infarcted area, thus possibly protecting the ischemic brain tissues through this mechanism.

Topics: Animals; Behavior, Animal; Benzofurans; Brain Ischemia; Cerebral Infarction; Intercellular Signaling Peptides and Proteins; Male; Neurologic Examination; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

To explore the effect of 3-n-butylphthalide pretreatment on the delayed neuronal death(DND) and the expreesion of heat shock protein70 (HSP70) in rat hippocampus after ischemia/ reperfusion.. All rats were randomly divided into sham group (n = 36), total cerebral ischemia (TCI) group (n = 36), butylphthalide (NBP) group (n = 6), NBP + TCI group( n = 36), quercetin + NBP + TCI group (n = 6), dimethyl sulfoxide (DMSO) + NBP + TCI group (n = 6). The model of total cerebral ischemia/reperfusion was established by blocking vertebral arteries and carotid arteries. In sham group, TCI group and NBP group, the animals were further divided into instantly, 6 h, 12 h, 1 d, 3 d, 5 d groups according to the time interval after sham operation or TCI. Histological changes of the hippocampus were evaluated using thionin staining under light microscope by determining the delayed neuronal death (DND) and the expression of HSP70 was assayed using immunohistochemistry.. NBP pretreatment could reduce delayed neuronal death in CA1 of hippocampus induced by TCI-reperfusion injury in rats, and up-regulated the expression of HSP70 in CA1 hippocampus of brain ischemic/reperfusion for 5 days. Quercetin blocked the acquirement of the brain ischemic tolerance induced by NBP preconditioning.. 3-n-butylphthalide (NBP) prevents the neurons from ischemia/reperfusion injury through upregulating the expression of HSP70.

Topics: Animals; Benzofurans; CA1 Region, Hippocampal; Cell Death; Cerebral Infarction; HSP70 Heat-Shock Proteins; Ischemic Preconditioning; Neurons; Rats; Rats, Wistar; Reperfusion Injury

The aim of this study was to explore the effect of butylphthalide on the brain edema, blood-brain barrier of rats of rats after focal cerebral infarction and the expression of Rho A. A total of 195 sprague-dawley male rats were randomly divided into control group, model group, and butylphthalide group (40 mg/kg, once a day, by gavage). The model was made by photochemical method. After surgery 3, 12, 24, 72, and 144 h, brain water content was done to see the effect of butylphthalide for the cerebral edema. Evans blue extravasation method was done to see the changes in blood-brain barrier immunohistochemistry, and Western blot was done to see the expression of Rho A around the infarction. Compared with the control group, the brain water content of model group and butylphthalide group rats was increased, the permeability of blood-brain barrier of model group and butylphthalide group rats was increased, and the Rho A protein of model group and butylphthalide group rats was increased. Compared with the model group, the brain water content of butylphthalide group rats was induced (73.67 ± 0.67 vs 74.14 ± 0.46; 74.89 ± 0.57 vs 75.61 ± 0.52; 77.49 ± 0.34 vs 79.33 ± 0.49; 76.31 ± 0.56 vs 78.01 ± 0.48; 72.36 ± 0.44 vs 73.12 ± 0.73; P < 0.05), the permeability of blood-brain barrier of butylphthalide group rats was induced (319.20 ± 8.11 vs 394.60 ± 6.19; 210.40 ± 9.56 vs 266.40 ± 7.99; 188.00 ± 9.22 vs 232.40 ± 7.89; 288.40 ± 7.86 vs 336.00 ± 6.71; 166.60 ± 6.23 vs 213.60 ± 13.79; P < 0.05), and the Rho A protein of butylphthalide group rats was decreased (western blot result: 1.2230 ± 0.0254 vs 1.3970 ± 0.0276; 1.5985 ± 0.0206 vs 2.0368 ± 0.0179; 1.4229 ± 0.0167 vs 1.7930 ± 0.0158;1.3126 ± 0.0236 vs 1.5471 ± 0.0158; P < 0.05). The butylphthalide could reduce the brain edema, protect the blood-brain barrier, and decrease the expression of Rho A around the infarction.

Topics: Animals; Benzofurans; Blood-Brain Barrier; Brain; Brain Edema; Cerebral Cortex; Cerebral Infarction; Disease Models, Animal; Immunohistochemistry; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; rhoA GTP-Binding Protein; Time Factors; Water

SMND-309 is a novel derivative of salvianolic acid B, and has shown protective effects against rat cortical neuron damage in vitro and in vivo. However the molecular mechanisms through which SMND-309 affords this protection are unclear. The present study aimed to investigate the mechanisms associated with the protective activities of SMND-309 in a cerebral ischemia and reperfusion injury rat model. In this study, we used AG490, a specific inhibitor of the signaling pathway involving the Janus Kinase 2 (JAK2)/Signal Transducers and Activators of Transcription 3 (STAT3) signaling molecules and suramin, a potent inhibitor of vascular endothelial growth factor (VEGF), to investigate the mechanisms of SMND-309. The cerebral ischemia and reperfusion injury model was induced by performing middle cerebral artery occlusion (MCAO) in the rats. SMND-309 mitigated the effects of ischemia and reperfusion injury on brain by decreasing the infract volume, improving neurological function, increasing the survival of neurons and promoting angiogenesis by increasing the levels of erythropoietin (EPO), erythropoietin receptor (EPOR), phosphorylated JAK2 (P-JAK2), phosphorylated STAT3 (P-STAT3), VEGF and VEGF receptor 2 (Flk-1) in the brain. Our results suggest that SMND-309 provides significant neuroprotective effects against cerebral ischemia and reperfusion injury. The mechanisms of this protection may be attributed to the increased VEGF expression occurring from the JAK2/STAT3 pathway, activated by the increased EPO/EPOR expression in the brain.

Topics: Animals; Axons; Benzofurans; Brain; Brain Ischemia; Caffeic Acids; Cerebral Infarction; Dendrites; Erythropoietin; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Janus Kinase 2; Male; Neovascularization, Physiologic; Neuroprotective Agents; Phosphoproteins; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Recovery of Function; Reperfusion Injury; Signal Transduction; STAT3 Transcription Factor; Survival Analysis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Water

The protective effect of MDL 74,180 (2,3-dihydro-2,2,4,6, 7-pentamethyl-3-(4-methylpiperazino)-methyl-1-benzofuran-5-ol dihydrochloride) and alpha-tocopherol analogue free radical scavenger, against cerebral ischaemia and reperfusion in conscious rats has been demonstrated. Tissue damage following middle cerebral artery occlusion (2 h) and reperfusion (8 days) was decreased by MDL 74,180 (0.1 and 1.0 mg/kg per h) infusion beginning 15 min before the onset of reperfusion and continuing for 2 h into the reperfusion period, in a dose-related manner. Nitroxide radical adducts, characterized and quantified by electron spin resonance spectroscopy, were formed on the addition of spin traps to homogenized rat brain tissue previously subjected to global ischaemia and reperfusion. The primary oxidative chain free radicals form diamagnetic intermediates whose slow homolytic decomposition subsequently yields the observed stable spin adducts. Infusion of MDL 74,180 (1-10 mg/kg per h) beginning 15 min before the induction of global cerebral ischaemia (20 min) until the end of reperfusion (5 min), led to a dose-dependent reduction in the final concentration of spin adducts.

Topics: Animals; Benzofurans; Brain Chemistry; Brain Ischemia; Cerebral Arteries; Cerebral Infarction; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Free Radicals; Male; Piperazines; Rats; Rats, Wistar; Reperfusion Injury; Spin Labels

dl-3-n-Butylphthalide (NBP) was known to have improving effect on brain energy metabolism after ischemia insult. The purpose of this study is to determine if the drug has protective action against ischemic neuronal damage. In the present study, the effect of NBP on cerebral infarction and neurological deficits after middle cerebral artery occlusion (MCAO) in rats was investigated. Focal cerebral ischemia was produced by permanent occlusion of the proximal portion of the right middle cerebral artery (MCA) according to the technique of Tamura. The infarct area was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining technique. The extent of neurological deficits was evaluated by the method of Bederson. The histological changes in neuronal change after MCAO in rats were also studied. The results indicate that the infarct area and the score of neurological deficits after MCAO were reduced significantly following intraperitoneal pretreatment or pre- and post-treatment with NBP 20 mg . kg-1. The treatment with NBP 10 or 20 mg . kg-1(i.p.), or 20,40 or 80 mg . kg-1 (po) 15 min and even 2 h (20 mg . kg-1, i.p.) after MCAO also markedly reduced the infarct area and the score of neurological deficits. However, no effect was found when NBP (20 mg . kg-1) was injected intraperitoneally 4 h after MCAO. MK-801 (0.5 mg . kg-1, i.p.), a non-competitive antagonist of NMDA receptor, significantly reduced the size of infarction and the score of neurological deficits in rats subjected to MCAO. The potency of NBP in reducing the infarct area and neurological deficits was found to be quite similar to that of MK-801 (0.5 mg . kg-1, i.p.). No neuroprotective effect of nimodipine (1.0 mg . kg-1, sc) was found. Generally, the potency of NBP in protecting rats from ischemic neurological damage is equal to that of MK-801 and is more powerful than that of Nimodipine. Side effects of NBP in behavior was not found. Therefore, NBP seems to be a hopeful drug for the treatment of stroke.

Topics: Animals; Behavior, Animal; Benzofurans; Cerebral Infarction; Dizocilpine Maleate; Male; Neuroprotective Agents; Nimodipine; Rats; Rats, Wistar; Vasodilator Agents

The neuroprotective efficacy of the kappa-opioid agonist enadoline (CI-977) was examined in two acute rat models of focal cerebral ischaemia [non-recovery (4 h) and recovery (24 h)]. In the non-recovery model, Sprague-Dawley rats were anaesthetized throughout the study period. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA). The amount of early ischaemic damage was assessed in coronal sections at nine pre-determined stereotaxic planes. Enadoline at doses of 0.1, 0.3 and 1.0 mg/kg (n = 8), administered s.c. 30 min prior to ischaemia, produced dose-dependent amelioration of cortical damage. Importantly, enadoline had no significant effect on any of the physiological parameters monitored (blood pressure, blood gases, glucose, pH). In the recovery model the left MCA was permanently occluded under isoflurane anaesthesia. Animals were allowed to recover and were killed 24 h later. The amount of ischaemic brain damage and swelling was assessed histologically. In this model pretreatment with enadoline at either 0.1, 0.3, or 1.0 mg/kg s.c. was followed by continuous s.c. infusion at 0.017, 0.05 or 0.17 mg/kg/h respectively (n = 8-17). Enadoline produced dose-dependent reductions in the volumes of infarction and brain swelling; the greatest reductions were seen at 1.0 mg/kg plus 0.17 mg/kg/h in both infarction (reduced by 37.4% from controls) and swelling (reduced by 47.8%). Therefore the kappa-opioid agonist enadoline affords dose-dependent neuroprotection in both the non-recovery and recovery models of focal cerebral ischaemia in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Benzofurans; Brain; Brain Edema; Brain Ischemia; Cerebral Infarction; Dose-Response Relationship, Drug; Male; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa

The effect of a novel, highly potent and selective kappa-opioid receptor agonist CI-977 upon ischaemic brain damage and brain swelling has been examined in a rat model of focal cerebral ischaemia. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA) during a brief period of halothane anaesthesia. The animals were sacrificed 24 h after MCA occlusion and the amount of ischaemic brain damage and swelling was assessed in coronal sections at 8 predetermined stereotactic planes. Treatment with CI-977 (0.03, 0.3 or 3 mg/kg), initiated 30 min prior to MCA occlusion (and at multiple times thereafter) produced dose-dependent reductions in the volumes of infarction and of brain swelling, with the most marked reductions being noted with CI-977 (0.3 mg/kg) in both infarction (reduced by 38% from controls; P less than 0.02) and swelling (reduced by 31%; P less than 0.002). There was an excellent correlation between the volume of brain swelling and ischaemic damage which was similar with saline-treated and CI-977-treated animals (overall correlation coefficient r = 0.896). These results indicate that CI-977 is effective in reducing infarction in a model of focal cerebral ischaemia, and that the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.

Topics: Animals; Benzofurans; Brain Edema; Cerebral Infarction; Disease Models, Animal; Ischemic Attack, Transient; Male; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa