Treatment Of Ischemic Cerebrovascular Disease Research Articles

Idiopathic hypereosinophilic syndrome presenting as capsular warning syndrome: A case report and literature review.

Few reports of idiopathic hypereosinophilic syndrome exist presenting as ischemic cerebrovascular disease, and the majority are watershed infarction. We report the first case of idiopathic hypereosinophilic syndrome that has clinical features of capsular warning syndrome lasting 6 weeks. A 26-year-old man complained of recurrent right limb weakness, accompanying slurred speech, and right facial paresthesia. The patient was diagnosed with idiopathic hypereosinophilic syndrome (IHES). Adequate glucocorticoid and anticoagulant treatments were given. The patient's motor ability improved, and he was discharged 2 weeks later. Muscle strength in the right-side extremities had fully recovered at a 3-month follow-up after discharge. This case suggests that idiopathic hypereosinophilic syndrome should be considered as a cause of capsular warning syndrome, and the dose of glucocorticoid and the efficacy evaluation index needs to be reevaluated for the treatment of ischemic cerebrovascular disease associated with idiopathic hypereosinophilic syndrome.

Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria

Mitochondrial dysfunction and subsequent accumulation of reactive oxygen species (ROS) are key contributors to the pathology of ischemic cerebrovascular disease. Therefore, elimination of ROS and damaged mitochondria is crucial for the effective treatment of this disease. For this purpose, we designed an inhalation nanotherapeutic agent, P/D@Mn/Co3O4, to treat ischemic cerebrovascular disease. Mn/Co3O4 effectively removed excess ROS from cells, reduced acute cellular oxidative stress, and protected neural cells from apoptosis. Furthermore, it depleted the H+ surrounding mitochondria and depolarized the mitochondrial membrane potential, inducing mitophagy and eliminating abnormal mitochondria, thereby avoiding the continuous overproduction of ROS by eliminating the source of ROS regeneration. On intranasal administration, Mn/Co3O4 encapsulated by platelet membranes and 2,3-(dioxy propyl)-trimethylammonium chloride can bypass the blood–brain barrier, enter the brain through the trigeminal and olfactory pathways, and target inflammatory regions to remove ROS and damaged mitochondria from the lesion area. In rat models of stroke and vascular dementia, P/D@Mn/Co3O4 effectively inhibited the symptoms of acute and chronic cerebral ischemia by scavenging ROS and damaged mitochondria in the affected area. Our findings indicate that the nanotherapeutic agent developed in this study can be used for the effective treatment of ischemic cerebrovascular disease.

Efficacy of modified EDAS combined with a superficial temporal fascia attachment-dural reversal surgery for the precise treatment of ischemic cerebrovascular disease.

To investigate the potential therapeutic benefits of Modified EDAS combined with superficial temporal fascia attachment-dural reversal surgery for the treatment of ischemic cerebrovascular disease. Retrospective analysis was made on the clinical data of 33 patients with ischemic cerebrovascular disease, who were admitted to the Neurological Diagnosis and Treatment Center of the Second Affiliated Hospital of Xinjiang Medical University from December 2019 to June 2021. All patients were treated with Modified EDAS combined with superficial temporal fascia attachment-dural reversal surgery. At 3 months after operation, the outpatient department rechecked the patient's head CT perfusion imaging (CTP) to understand the intracranial cerebral blood flow perfusion. The DSA of the patient's head was re-examined 6 months after operation to observe the establishment of collateral circulation. The improved Rankin Rating Scale (mRS) score was used to evaluate the good prognosis rate of patients at 6 months after surgery. The mRS score ≤2 was defined as good prognosis. The preoperative cerebral blood flow (CBF), local blood flow peak time (rTTP), and local mean transit time (rMTT) of 33 patients were 28.235 ml/(100 g·min), 17.702 s, 9.796 s, respectively. At 3 months after surgery, CBF, rTTP, and rMTT were 33.743 ml/(100 g·min), 15.688, and 8.100 s, respectively, with significant differences (P < 0.05). At 6 months after operation, the establishment of extracranial and extracranial collateral circulation was observed in all patients by re-examination of head DSA. At 6 months after operation, the good prognosis rate was 81.8%. The Modified EDAS combined with superficial temporal fascia attachment-dural reversal surgery is safe and effective in the treatment of ischemic cerebrovascular disease, which can significantly increase the establishment of collateral circulation in the operation area and improve the prognosis of patients.

Network Meta-analysis of single Hirudo prescriptions in treatment of ischemic cerebrovascular disease

This study intended to evaluate the efficacy and safety of single Hirudo prescriptions in the treatment of ischemic cerebrovascular disease(ICVD) by frequency network Meta-analysis and traditional Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library databases were searched to collect the randomized controlled trial(RCT) of single Hirudo prescriptions for ICVD from the inception of the databases to May 2022. The quality of the included literature was evaluated by Cochrane risk of bias tool. Finally, 54 RCTs and 3 single Hirudo prescriptions were included. Statistical analysis was conducted by RevMan 5.3 and Stata SE 15. Network Meta-analysis showed that in terms of the clinical effective rate, the surface under the cumulative ranking curve(SUCRA) of intervention measures was as follows: Huoxue Tongmai Capsules+conventional treatment&gt;Maixuekang Capsules+conventional treatment&gt;Naoxuekang Capsules+conventional treatment&gt;conventional treatment. Traditional Meta-analysis revealed that in terms of the safety of ICVD treatment, Maixuekang Capsules+conventional treatment had higher safety than conventional treatment alone. According to the network Meta-analysis and traditional Meta-analysis, it was found that conventional treatment combined with single Hirudo prescriptions improved the clinical efficacy of ICVD patients, and compared with that of conventional treatment alone, the incidence of adverse reactions of combined treatment was low and the safety was high. However, the methodological quality of the articles included in this study was generally low and there were large differences in the number of articles on the three combined medication. Therefore, the conclusion of this study needed to be confirmed by subsequent RCT.

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury.

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms. Fingolimod (FTY-720) is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities, and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases. In the current research, the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model. Our results revealed that FTY-720 markedly decreased infarct volume, promoted neurological function recovery, and weakened the blood-brain barrier permeability of ischemic rats. The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels. These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling.

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia. However, whether there is a synergistic effect between the two remains unclear. In this study, we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes (MSC-exos) via the tail vein and underwent 14 successive days of treadmill exercise. Neurological assessment, histopathology, and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume, evident synaptic formation and axonal regeneration, and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment. These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone. Mechanistically, further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling. These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment, which may be related to activation of the JNK1/c-Jun signaling pathway. This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

Studies on Chemical Characterization of Ginkgo Amillaria Oral Solution and Its Drug-Drug Interaction With Piceatannol 3'-O-β-D-Glucopyranoside for Injection.

Ginkgo Amillaria oral solution (GAO) is commonly used for the treatment of cardiovascular and cerebrovascular diseases in China. Piceatannol-3′-O-β-D-glucopyranoside for injection (PGI) is mainly used for the prevention and treatment of ischemic cerebrovascular diseases. With the spread of cerebrovascular disease, the possibility of combining the two drugs has increased; however, there is no research on the drug–drug interaction (DDI) between these two medicines. In this paper, an ultrahigh-performance liquid chromatography/quadrupole–orbitrap mass spectrometry (UHPLC/Q-Orbitrap MS) method was established to characterize the chemical constituents of GAO first; 62 compounds were identified or tentatively identified based on their retention time (RT), MS, and MS/MS data. Nine main compounds were determined by ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, incubation with liver microsomes in vitro was fulfilled; the results showed that GAO had a significant inhibitory effect on UGT1A9 and UGT2B7 (p < 0.05), and PGI was mainly metabolized by UGT1A9. The identification results of in vivo metabolites of PGI showed that PGI mainly undergoes a phase II binding reaction mediated by UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) in vivo. Therefore, pharmacokinetic studies were performed to investigate the DDI between GAO and PGI. The results showed that the AUC (p < 0.05) and T1/2 (p < 0.05) of PGI in vivo were significantly increased when administered together with GAO, whereas the CL was significantly decreased (p < 0.05). The exploration of in vitro and in vivo experiments showed that there was a DDI between GAO and PGI.

Berberine protects against chronic cerebral hypoperfusion-induced cognitive impairment and hippocampal damage via regulation of the ERK/Nrf2 pathway

Vascular cognitive impairment caused by chronic cerebral hypoperfusion (CCH) seriously affects the quality of life of elderly patients and places a great burden on society and family. With the development of traditional Chinese medicine (TCM), TCM approaches to the prevention and treatment of senile ischemic cerebrovascular disease has received increasing attention. In this study, rats with bilateral common carotid artery occlusion (BCCAO) were treated with berberine (BBR). Their learning and memory function, neuronal injury and repair, the extracellular regulatory protein kinase (ERK)/nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, and impairment and improvement of the blood–brain barrier (BBB) were evaluated. This study found that BBR can alleviate the pathological injury to the brain, reduce neuronal loss and promote neuronal cell survival after CCH by interfering with the ERK/Nrf2 signaling pathway. BBR can reduce BBB injury in CCH rats by inhibiting the expression of VEGF-A and MMP-9 in plasma, which reveals a protective effect of BBR on vascular cognitive impairment. This study provides a new research direction for BBR in the treatment of ischemic cerebrovascular disease.

Study on the Mechanism of Üstikuddus Sherbiti in Ischemic Cerebrovascular Diseases: Based on Network Pharmacology.

This paper aims to study the potential biological mechanism of Üstikuddus Sherbiti (ÜS) in the treatment of ischemic cerebrovascular diseases (ICVD) by the network pharmacology method. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain effective constituents of ÜS by screening eligible oral utilization, drug similarity, and blood-brain barrier permeability threshold. By drug target prediction and stroke treatment target mining, 2 target data sets were analyzed to find intersection targets and the corresponding constituents were used as active constituents. An active constituent target network and an effective constituent target network were constructed by using Cytoscape 3.7.2 software. Degree parameters of the effective constituent target network were analyzed to find important effective constituents and targets. Through protein-protein interaction (PPI) analysis/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, potential signaling pathways of ÜS in ischemic stroke were found out. AutoDock was used for molecular docking verification. A total of 90 active constituents of ÜS were screened out. There were 10 active constituents against ICVD, including quercetin, luteolin, kaempferol, and naringenin, and 10 important targets for anticerebral ischemia, namely, PIK3CA, APP, PIK3R1, MAPK1, MAPK3, AKT1, PRKCD, Fyn, RAC1, and NF-κB1. Based on the protein interaction network, the important targets of ÜS were significantly enriched in PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction pathway, Ras signaling pathway, etc. ÜS in ICVD has characteristics like multiple targets, multiple approaches, and multiple pathways. Results of molecular docking showed that the active components in ICVD had a good binding ability with the key targets. Its main biological mechanism may be related to the PI3K-Akt and Ras-MAPK centered signaling pathway. Our study demonstrated that ÜS exerted the effect of treating ICVD by regulating multiple targets and multiple channels with multiple components through the method of network pharmacology and molecular docking.

Optimization of source-detector separation for non-invasive regional cerebral blood flow sensing

The detection of cerebral blood flow (CBF) has important clinical value for the diagnosis and treatment of ischemic cerebrovascular disease. The chronic changes of regional cerebral blood flow (rCBF) need long-term detection in specific cerebrovascular diseases such as Alzheimer's disease. In this paper, the optimal source-detector separation (SDS) in optical heterodyne detection combined with interferometric diffusing wave spectroscopy (OHD-iDWS) was studied. Changing the thickness of the skull and the absorption coefficient of the scalp layer, the Polarized Monte Carlo (PMC) method was used to analyze the influence of the average penetration depth and the number of polarized photons on SDS. In addition, the dynamic phantom experiments were used to evaluate the performance of the OHD-iDWS system. In this study, the system further explored the optimal SDS by distinguishing different flow rates, which provided an optimal method for SDS within 20 mm. Using PMC simulation and dynamic phantom experiments to find out the optimal SDS of rCBF sensing, it provides a theoretical basis for more effective detection of rCBF.

10-O-(N N-Dimethylaminoethyl)-Ginkgolide B Methane-Sulfonate (XQ-1H) Ameliorates Cerebral Ischemia Via Suppressing Neuronal Apoptosis

Objectives: The 10-O-(N N-dimethylaminoethyl)-ginkgolide B methane-sulfonate (XQ-1H) is an effective novel drug for the treatment of ischemic cerebrovascular disease derived from Ginkgolide B, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, whether XQ-1H exerts neuroprotective effect via regulating neuronal apoptosis and the underlying mechanism remain to be elucidated. Materials and methods: This study was aimed to investigate the neuroprotective effect of XQ-1H in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and the oxygen glucose deprivation/reoxygenation (OGD/R) induced neuronal apoptosis on pheochromocytoma (PC-12) cells. Results: The results showed that administration of XQ-1H at different dosage (7.8, 15.6, 31.2 mg/kg) reduced the brain infarct and edema, attenuated the neuro-behavioral dysfunction, and improved cell morphology in brain tissue after MCAO/R in rats. Moreover, incubation with XQ-1H (1 µM, 3 µM, 10 µM, 50 µM, 100 µM) could increase the cell viability, and showed no toxic effect to PC-12 cells. XQ-1H at following 1 µM, 10 µM, 100 µM decreased the lactate dehydrogenase (LDH) activity and suppressed the cell apoptosis in PC-12 cells exposed to OGD/R. In addition, XQ-1H treatment could significantly inhibit caspase-3 activation both in vivo and in vitro, reciprocally modulate the expression of apoptosis related proteins, bcl-2, and bax via activating PI3K/Akt signaling pathway. For mechanism verification, LY294002, the inhibitor of PI3K/Akt pathway was introduced the expressions of bcl-2 and phosphorylated Akt were down-regulated, the expression of bax was up-regulated, indicating that XQ-1H could alleviate the cell apoptosis through activating the PI3K/Akt pathway. Conclusions: Our findings demonstrated that XQ-1H treatment could provide a neuroprotective effect against ischemic stroke induced by cerebral ischemia/reperfusion injury in vivo and in vitro through regulating neuronal survival and inhibiting apoptosis. The findings of the study confirmed that XQ-1H could be develop as a potential drug for treatment of cerebral ischemic stroke.

Clinical Application of Medical Imaging in Neurointerventional Treatment of Brain Diseases

The incidence rate of cerebral infarction is high, and the risk of death is also grown significantly with age. Atherosclerotic stenosis is a part of the main causes of cerebral infarction. The effect of drug conservative therapy is not ideal. Interventional therapy is tantamount to send the guidewire, catheter and so on to the lesion site using imaging means, and operates the local area to achieve the purpose of a precise treatment. Therefore, it is important to explore the characteristics and high-risk factors of complications for clinical prevention and guidance of treatment righteousness. This study was to investigate the clinical effect of digital subtraction angiography (DSA) in the treatment of ischemic cerebrovascular disease. Also, this paper discusses the clinical effect of digital subtraction angiography (DSA) in the treatment of cerebral infarction. It has been proved that the application of flat detector CT in the interventional room can not only obtain high-quality 3D angiography (3D rotational angiography), but also display the vessels and high-density structures (skeleton, vascular clamp, coil, stent, and ingenious plaque). Fd-ct has also been proved to be able to perform 3D reconstruction on the stent placed in the patient’s heart and the stent of the external carotid artery. Compared with multi-slice spiral CT, the stent is much clearer and can be used to evaluate the soil and stent placement in the treatment of aneurysms.

Dl-3-n-Butylphthalide Alleviates Demyelination and Improves Cognitive Function by Promoting Mitochondrial Dynamics in White Matter Lesions.

White matter lesions (WMLs) are a type of cerebrovascular disorder accompanied by demyelination and cognitive decline. Dl-3-n-butylphthalide (D1-NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases, although the function of DI-NBP on WML is still not clear. This study aims to investigate whether DI-NBP affects cognitive function and ameliorates demyelination in a model of WML. The bilateral carotid artery stenosis (BCAS) mouse model and in vitro brain slice cultures with low glucose and low oxygen (LGLO) treatment were adopted. The Dl-NBP was administered intragastrically for 28 days after BCAS or added at a dose of 50 μm for 48 h after LGLO. Spatial learning and memory were evaluated by an eight-arm radial maze. Demyelination was detected using a TEM. Mitochondrial dynamics were assessed by time-lapse imaging in the cultured brain slices. The function of the synapse was evaluated by the patch clamp technique. In BCAS mice, obvious demyelination and cognitive decline were observed, while both were significantly relieved by a high-dose D1-NBP treatment (100 mg/kg). Along with demyelination, mitochondrial accumulation in the axons was significantly increased in the BCAS mice model, but with the treatment of a high-dose D1-NBP, mitochondrial accumulation was mitigated, and the anterograde/retrograde transport of mitochondria was increased. Following the improved anterograde/retrograde transport of mitochondria, the synapse activity was significantly upregulated while the reactive oxygen species (ROS) generation was remarkably decreased in the cultured brain slices. In addition, we identified syntaphilin (SNPH) as the downstream target of D1-NBP. The overexpression of SNPH mediated the effects of D1-NBP in mitigating axonal mitochondrial accumulation. In conclusion, the D1-NBP treatment significantly relieved demyelination and improved spatial learning and memory in the WML model by promoting mitochondrial dynamics. These neuroprotective effects of D1-NBP were mediated by inhibiting the mitochondrial arching protein, SNPH, which provided a potential therapeutic target for WML.

Efficacy of neurointervention combined with intravenous thrombolysis in the treatment of ischemic cerebrovascular disease and its influence on neurological function and prognosis of patients.

The present study aimed to investigate the efficacy of neurointervention combined with intravenous thrombolysis in the treatment of ischemic cerebrovascular disease (ICD) and its influence on the neurological function and prognosis of patients. A total of 119 patients with ICD admitted to Xinxiang Central Hospital (Xinxiang, China) from May 2013 to September 2015 were selected. Among them, 65 patients were enrolled in the control group and treated with intravenous thrombolysis, whereas the other 54 patients were enrolled in the observation group and were treated with intravenous thrombolysis combined with neurointervention. The National Institute of Health Stroke Scale (NIHSS) system was used to evaluate the neurological function of patients after treatment. Kaplan-Meier survival curve analysis was carried out to assess the survival of patients. The total effective rate, complications, vascular recanalization and the hospitalization time after treatment were compared between the two groups. The NIHSS scores at 1, 3 and 6 months after treatment were statistically lower in the observation group than those in the control group (P<0.05). The total effective rate and total vascular recanalization in the observation group were higher than those of the control group (P<0.05). The incidence of complications in the observation group was statistically lower than that in the control group (P<0.05). In conclusion, neurointervention combined with intravenous thrombolysis can not only effectively improve the diseased blood vessels of patients and restore the damaged nerve function, but also reduce the incidence of complications. Moreover, neurointervention combined with intravenous thrombolysis is safe and can ensure a better quality of life of patients.

High frequency electrical field-ultrashort wave therapy for treatment of cerebral ischemia/reperfusion injury in rats*: Histopathological evaluation

Abstract BACKGROUND Ultrashortwave (USW) therapy may be a new method for treatment of ischemic cerebrovascular diseases. It is necessary to study its treatment time window. OBJECTIVE To observe the effect of USW on reperfusion injury after occlusion of the middle cerebral artery (MCAO) in rats and discuss its acting mechanisms and best occasion. DESIGN Randomized controlled observation, animal experiment. SETTING Laboratory of Department of Rehabilitation Medicine, First Hospital Affiliated to China Medical University. MATERIALS Sixty-six healthy Wistar rats of either gender and of clean grade, aged 18 – 20 weeks, weighing from 250 to 300 g, were provided by the Experimental Animal Center of China Medical University. An USW device (Shanghai Electrical Device Company) with the frequency of 40.68 MHz and the maximum output power of 40 W, and the first channel power controlled at about 11 W was used in this study. Output power was determined by photometry. METHODS Sixty-six rats were randomly divided into 3 groups: Sham-operation group (n = 6): The suture was inserted only 1.0 depth during operation, which did not cause MACO; Model group (n = 12): The USW treatment procedure was performed with the power off on the model rats; USW treatment group (n = 48): The 48 rats were randomly divided into modeling 0, 6, 12 and 18 hours 4 subgroups. USW therapy without heat was used on the head of rats for 10 minutes at each time point. Twelve rats in USW treatment group were decapitated following treatment at each time point, and then their brain tissues were harvested. The rat brain tissues in other groups were harvested by decapitation at 24 hours after modeling. When the rats were awake, the neurologic deficit was scored by Zea-Longa five-point scale (a score of 0 indicated no neurologic deficit, a score of 1 indicated failure to extend left paw fully, a score of 2 indicated circling to the left, and a score of 3 indicated falling to the left, and rats with a score of 4 did not walk spontaneously and has a depressed level of consciousness.) Rats which still survived at 24 hours and was scored 1 and 2 on the neurologic scoring were involved in the analysis. (1) Determination of cerebral water content: Cerebral water contents of healthy and injured hemisphere were determined by wet/dry weighing method. Cerebral water content (100%) = (1 – dry/wet weight) × 100%. (2)Infarction volume: The brain tissue was sliced into 2 mm sections and each section was stained with 20 g/L 2,3,5-triphenyltetrazolium chloride (TTC) by TTC staining technique for 30 minutes in a water bath at 37 °C. Then, the section was fixed in 100 g/L formaldehyde for 10 minutes. The infarction volume was analyzed by using an imaging analyzer. (3) Preparation of light microscopic sample: The rat brain tissue fixed by 100 g/L neutral formaldehyde and stained with TTC, were gradiently dehydrated with alcoholic, embedded with paraffin, sliced and stained by HE, finally, the sections were observed under the light microscope. MAIN OUTCOME MEASURES Cerebral water content, cerebral infarction volume and cerebral histomorphology of rats in each group. RESULTS Sixty-six rats were involved in the final analysis. (1) Cerebral water content: There were no significant differences of cerebral water content in healthy hemisphere among groups (P > 0.05). Cerebral water content of injured hemisphere in the model group and at modeling 0, 6, 12 and 18 hours in the USW treatment group was (81.50±0.74) %, (81.02±0.83) %, (79.78±0.70) %, (79.74±0.84) %, (79.39±1.06) %, respectively, which was significantly higher than that in the sham-operation group [(78.09±0.52) %, P CONCLUSION USW may play a protective effect on cerebral ischemia/reperfusion injury by decreasing brain edema and/or cerebral infarction volume. The treatment action of USW may start at 6 hours after reperfusion, and the best occasion of application may be at 18 hours after reperfusion.

Similarities and differences between Ginkgo biloba and Panax notoginseng in treatment of ischemic cerebrovascular disease

Ginkgo biloba and Panax notoginseng are both herb medicines for cerebrovascular disease, and play an active role in treating ischemic cerebrovascular disease(ICVD). Their mechanisms of action include antioxidant stress, nerve protection, vascular protection. According to the comparative study of literatures, G. biloba has a certain protective effect from the early stage of free radical formation throughout the whole process of causing cell inflammation and apoptosis in antioxidant stress; while P. notoginseng has mainly anti-inflammatory, anti-apoptosis effects. In the nerve protection and repair of nerve damage caused by glutamate, both could promote neurogenesis, repair damaged axons and protect nerve cells. In addition, G. biloba could also relieve neurotoxicity caused by glutamate damage, while P. notoginseng have a unique effect in repairing blood-brain barrier(BBB) and blood vessel regeneration. In clinic, they are used as auxiliary drugs in combination with thrombolytic therapy, and play curative effects in alleviating inflammation, eliminating edema, improving the cure rate and the prognosis. For cerebral diseases caused by chronic cerebral hypoperfusion, G. biloba could reduce inflammation and improve cognition. In addition, G. biloba could protect neurocyte by adjusting the secretion of dopamine in vivo, and has a certain effect on antidepressant diseases, which however needs further studies.

3‑N‑Butyphthalide improves learning and memory in rats with vascular cognitive impairment by activating the SIRT1/BDNF pathway.

Vascular cognitive impairment (VCI) is a type of cerebral vascular disorder that leads to learning and memory decline. VCI models can be induced by chronic cerebral hypoperfusion via permanent bilateral common carotid artery occlusion. 3-N-Butylphthalide (NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases. Silent information regulator 1 (SIRT1) plays an important role in memory formation and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that plays critical roles in promoting neuronal growth and injury repair. The present study was performed to investigate the effects and the underlying mechanism of NBP on learning deficits in a rat model of VCI. Rats were divided into a control group, model group, low-NBP-dose group (30 mg/kg/day), high-NBP-dose group (60 mg/kg/day), NBP + SIRT1 inhibitor group and NBP + BDNF inhibitor group. Rats were then subjected to Morris water maze and T-maze tests, which identified that NBP treatment significantly attenuated memory impairments in VCI rats. Molecular examination indicated that SIRT1 and BDNF expression levels in the hippocampus were increased by NBP treatment. However, NBP failed to ameliorate cognitive function after inhibition of the SIRT1/BDNF signaling pathway. In addition, NBP in combination with a SIRT1 inhibitor suppressed BDNF protein expression, but inhibition of BDNF did not inhibit SIRT1 protein expression in rats with VCI. The present results suggested that the neuroprotective effects of NBP on learning deficits in a rat model of VCI may be via regulation of the SIRT1/BDNF signaling pathway, in which SIRT1 may be the upstream signaling molecule. Therefore, the SIRT1/BDNF pathway could be a potential therapeutic target for VCI.

An MRI Study of Neurovascular Restorative After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Stroke.

Xiaoshuan enteric-coated capsule (XSEC) is a Chinese medicinal compound widely used for treatment of ischemic cerebrovascular diseases. Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. This study aimed to apply magnetic resonance imaging (MRI) to non-invasively assess whether EE could augment the therapeutic benefits of XSEC on post-ischemic neurovascular remodeling. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with XSEC and EE alone or combination for 30 consecutive days. Beam walking test and Morris water maze (MWM) test were performed to evaluate motor and cognitive function, respectively. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. Western blot and RT-PCR were used to detect the expressions of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the axon guidance molecules. Combination therapy with XSEC and EE significantly reduced cystic volume compared with XSEC and EE monotherapies. In line with this, combination treated rats performed better in the beam walking test and exhibited improved spatial memory in the probe trial of the MWM. Moreover, XSEC and EE combination treatment improved cerebral blood flow (CBF), amplified angiogenesis and upregulated VEGF protein levels. This proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum. Specifically, the combined therapy of XSEC and EE markedly increased the Netrin-1 and Robo-1 protein expression levels compared with vehicle group, while no difference was observed between XSEC or EE monotherapy and vehicle group. Together, these findings indicate that the combination of XSEC and EE benefits neurovascular reorganization. This correlates with restoration of CBF, promotion of neurogenesis and angiogenesis, and activation of the intrinsic axonal guidance molecules, thereby facilitating greater physical rehabilitation after ischemic stroke.

Advances in surgical treatment of ischemic cerebrovascular disease

Restoration of cerebral blood flow is particularly important for the treatment of ischemic cerebrovascular disease. It is notable that surgical approaches play a unique role in treating this devastating disease. Among them, mechanical thrombectomy facilitates rapid and effective recanalization of occluded intracranial large vessels causing ischemic stroke, which contributes to improvement of cerebral perfusion in the ischemic penumbra; decompressive craniectomy is an important therapeutic option for acute massive cerebral infarction, and the timing of surgery determines the final clinical outcomes; for carotid endarterectomy in carotid-artery stenosis, individualized surgical plan is important for the safety and effectiveness of the operation; in the surgical revascularization of Moyamoya disease, precise evaluation of clinical and radiological characteristics, optimal surgical strategies and accuracy of intraoperative judgment will yield maximal therapeutic effects; and hybrid surgery is feasible for the therapy of complex ischemic cerebrovascular diseases, such as extracranial/intracranial arteries tandem stenosis and symptomatic chronic total occlusion of carotid artery. This paper reviews recent technical and clinical advances in the surgical treatment of ischemic cerebrovascular disease.

Effect of Ginkgo biloba extract (EGb50) on mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation injury

Ischemic cerebrovascular disease and cerebral ischemia/reperfusion injury threaten the health of human being. We studied the protective effect of Ginkgo biloba extract 50 (EGb50) on the mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation (H/R) injury and explored its mechanisms, so as to provide new ideas for studies on the treatment for ischemic cerebrovascular disease. We established the H/R injury model in SH-SY5Y cells after administrating EGb50. Subsequently, the mitochondrial membrane potential and the concentration of intracellular Ca²⁺ were measured by flow cytometer. The levels of optic atrophy1 (Opa1) and dynamin-like protein 1 (Drp1) were evaluated by immunofluorescence and western blot. The results showed that the mitochondrial membrane potential was decreased and the level of intracellular Ca²⁺ was increased after H/R injury. Moreover, the expression of mitochondrial fusion protein Opa1 was decreased, while the expression of mitochondrial fission protein Drp1 was increased. However, EGb50 significantly increased the mitochondrial membrane potential and suppressed the level of intracellular Ca²⁺. In addition, EGb50 increased the expression of Opa1 and decreased the expression of Drp1. The results demonstrated that EGb50 has a neuroprotective effect on SH-SY5Y cells after H/R injury, and could improve the energy metabolism and mitochondrial function. The underlying mechanisms may be associated with the regulation of mitochondrial fusion and fission, which provided data support for the treatment of ischemic cerebrovascular disease with EGb50.