Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

OBJECTIVES: To investigate the efficacy of volume-guaranteed high-frequency oscillatory ventilation (HFOV-VG) in preterm infants with respiratory distress syndrome (RDS) and its impact on blood flow in the middle cerebral artery (MCA). METHODS: A prospective study was conducted on 120 preterm infants with RDS who were admitted to the Department of Neonatology at Qinhuangdao Maternal and Child Health Hospital from March 2020 to December 2023. According to the mode of ventilation, the infants were divided into two groups: a conventional mechanical ventilation (CMV) group (60 infants) and an HFOV-VG group (60 infants). The two groups were compared in terms of baseline data, MCA hemodynamic parameters, complications, and outcomes. RESULTS: Compared with the CMV group, the HFOV-VG group had significantly shorter durations of mechanical ventilation and hospital stay and a significantly higher overall response rate (P<0.05). The HFOV-VG group demonstrated significantly better peak systolic velocity, end-diastolic velocity, and mean flow velocity (P<0.05). The HFOV-VG group also exhibited significantly lower 28-day mortality rates and lower incidence rates of bronchopulmonary dysplasia and intraventricular hemorrhage than the CMV group (P<0.05). CONCLUSIONS HFOV-VG can effectively improve cerebral blood perfusion, reduce cerebrovascular resistance, shorten the durations of mechanical ventilation and hospital stay, and enhance overall treatment efficacy. It has significant advantages in reducing the risk of 28-day mortality, bronchopulmonary dysplasia, and intraventricular hemorrhage in preterm infants with RDS.
Humans ; High-Frequency Ventilation/adverse effects* ; Infant, Newborn ; Respiratory Distress Syndrome, Newborn/physiopathology* ; Female ; Middle Cerebral Artery/physiology* ; Male ; Prospective Studies ; Cerebrovascular Circulation ; Infant, Premature

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

OBJECTIVE: To explore the diagnosis and treatment of acute cerebral infarction following extracorporeal membrane oxygenation (ECMO) therapy in patients with cardiogenic shock to review the literature. METHODS: The clinical data of two patients with cardiogenic shock treated with veno-arterial ECMO (VA-ECMO) complicated with acute cerebral infarction admitted to department of intensive care unit (ICU) of Affiliated Hospital of Guizhou Medical University were retrospectively analyzed and the treatment experience was shared. RESULTS: Case 1 was a 46-year-old male patient who was admitted to the hospital on September 16, 2021, due to "repeated chest tightness, shortness of breath, syncope for 2+ years, and worsened for 15 days. Coronary artery angiography showed 3-vessel coronary artery disease lesions. On October 15, 2021, coronary artery bypass grafting (CABG), pericardial fenestration and drainage, thoracic closed drainage, femoral bypass, thoracotomy exploration, and sternal internal fixation were performed under support of extracorporeal circulation. After surgery, the heart rate was 180-200 bpm, the blood pressure could not be maintained, and the improvement was not obvious after active drug treatment. The right femoral artery and femoral vein were intubated, VA-ECMO support treatment was performed, and the patient was transferred to the ICU. Intra-aortic balloon pump (IABP) was treated on the day of transfer because the circulation could not be maintained. Due to acute cerebral infarction in the left hemisphere and right parieto-occipital lobe, subfalcine herniation, tentorial herniation, the patient ultimately died after withdrawing from ECMO. Case 2 was a 43-year-old male patient who was admitted to the hospital on June 29, 2021, with "fever for 8 days and vomiting for 4 days". Bedside ultrasound showed cardiac enlargement and diffuse wall motion reduction in the left and right ventricles. On June 30, 2021, the patient underwent catheterization through the right femoral artery and femoral vein, VA-ECMO support, and was transferred to ICU for treatment. Acute cerebral infarction on both sides of the cerebellum occurred, and after treatment, the patient was discharged with mild impairment of daily living ability. CONCLUSIONS Strengthen monitoring of anticoagulation; regular neurological examination of patients undergoing ECMO therapy; ECMO under light sedation or awake can be performed if the condition permitsif the condition permits, perform light sedation or awake ECMO, which helpful for the early detection of nervous system injury.
Male ; Humans ; Middle Aged ; Adult ; Shock, Cardiogenic/therapy* ; Extracorporeal Membrane Oxygenation ; Retrospective Studies ; Coronary Artery Bypass/adverse effects* ; Cerebral Infarction/therapy*

OBJECTIVE: To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke. METHODS: Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD₃ group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD₃ group were treated with intragastric administration of 1,25-dihydroxyvitamin D₃ (1,25-VitD₃) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex. RESULTS: Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD₃ group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD₃ group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex (P<0.01, P<0.05). CONCLUSION ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Ischemic Stroke ; Interleukin-10 ; Interleukin-6/genetics* ; Microglia ; Scalp ; Acupuncture Therapy ; Vitamins ; Infarction, Middle Cerebral Artery

BACKGROUND: The effect of arteriosclerotic intracranial arterial vessel wall enhancement (IAVWE) on downstream collateral flow found in vessel wall imaging (VWI) is not clear. Regardless of the mechanism underlying IAVWE on VWI, damage to the patient's nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow. The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow. METHODS: The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery (MCA) M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset. The patients were divided into 4 groups according to IAVWE and the stenosis ratio (Group 1, n = 17; Group 2, n = 19; Group 3, n = 13; Group 4, n = 14), and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling (3D-pCASL) and RAPID software. The National Institutes of Health Stroke Scale (NIHSS) scores of the patients were also recorded. Two-factor multivariate analysis of variance using Pillai's trace was used as the main statistical method. RESULTS: No statistically significant difference was found in baseline demographic characteristics among the groups. IAVWE, but not the stenosis ratio, had a statistically significant significance on the late-arriving retrograde flow proportion (LARFP), hypoperfusion intensity ratio (HIR), and NIHSS scores ( F = 20.941, P <0.001, Pillai's trace statistic = 0.567). The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables: LARFP ( R2 = 0.088, F = 10.899, P = 0.002), HIR ( R2 = 0.234, F = 29.354, P <0.001), and NIHSS ( R2 = 114.339, F = 33.338, P <0.001). CONCLUSIONS: Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits. It was an independent factor affecting downstream collateral flow and NIHSS scores, which should be a focus of future studies. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR2100053661.
Humans ; Constriction, Pathologic/pathology* ; Magnetic Resonance Imaging/methods* ; Middle Cerebral Artery/pathology* ; Tomography, X-Ray Computed

This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.
Rats ; Animals ; Astrocytes ; Brain Ischemia/metabolism* ; Brain ; Reperfusion Injury/metabolism* ; Infarction, Middle Cerebral Artery

This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.
Rats ; Animals ; NF-kappa B/metabolism* ; bcl-2-Associated X Protein ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Toll-Like Receptor 4/metabolism* ; Nimodipine/pharmacology* ; Interleukin-6 ; Rats, Wistar ; Signal Transduction ; Infarction, Middle Cerebral Artery ; Reperfusion Injury/prevention & control* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To explore the feasibility of using indocyanine green angiography in mapping the superficial temporal vessels and assisting design and harvesting of the superficial temporal artery based forehead flap. METHODS: A clinical data of 14 patients with facial soft tissue defects repaired with superficial temporal artery based forehead flaps between October 2015 and November 2022 was retrospectively analyzed. There were 9 males and 5 females with a median age of 9.5 years (range, 3-38 years). The forehead flaps were used to reconstruct facial soft tissue defects following excision of facial scar (8 cases) or congenital melanocyte nevus (6 cases). The size of defects ranged from 3 cm×2 cm to 24 cm×9 cm. Before operation, the indocyanine green angiography was used to map the superficial temporal artery and vein, and to analyze the relationship of the arteries and veins. The forehead flaps with unilateral superficial temporal fascia as the pedicle was transferred to repair the small facial defect in 2 cases. The facial pedicle contained the frontal branch of the superficial temporal artery and 2 cm of the superficial temporal fascia around the vessel, and the tiny accompanying vein of the frontal branch of the superficial temporal artery was used as the outflow of the flap. The forehead flaps with the skin pedicle including bilateral or unilateral superficial temporal fascia and the overlying skin was pre-expanded and transferred to repair the large facial defect in 12 cases. The skin pedicle contained the frontal branch of superficial temporal artery and one of main branches of superficial temporal vein. Among the 12 cases, the frontal branch of superficial temporal vein was used as the outflow in 4 cases, and the parietal branch was used as the outflow in 8 cases. The size of the flaps ranged from 3 cm×2 cm to 30 cm×13 cm. The skin pedicles were divided at 3 weeks after the flap transfer. RESULTS: Indocyanine green angiography could clearly showed the course and branching of the superficial temporal artery and vein. Individual differences existed in the location where the frontal branch of the superficial temporal artery entered the forehead. The superficial temporal vein had great variability and did not follow the artery. One patient had expander-related complication, which resulted in 3-cm flap necrosis. The necrotic tissue was debrided and repaired with skin grafting. The other flaps totally survived and the incisions healed by first intention. All patients were followed up 2-24 months, with a median of 11.5 months. The color, texture, and thickness of the flaps matched well with those of recipient sites. Hypertrophic scar was not observed in recipient or donor site. All patients were satisfied with the reconstructive outcomes. CONCLUSION Indocyanine green angiography can clearly visualize the course and the branches of the superficial temporal arteries and veins, which can help surgeons understand the position, distribution, and concomitant relationship of the superficial temporal vessels, and make a rational surgical plan of the forehead flap.
Male ; Female ; Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Temporal Arteries/surgery* ; Indocyanine Green ; Forehead/surgery* ; Retrospective Studies ; Skin Transplantation ; Angiography ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Treatment Outcome

Humans ; Infarction, Middle Cerebral Artery/surgery* ; Thrombectomy ; Thrombosis/etiology* ; Stents/adverse effects* ; Treatment Outcome