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

BACKGROUNDThe functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke.

METHODSRat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/ group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 × 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome.

RESULTSMCI-186 upregulated the expression of SDF-1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72 , P < 0.01) and the improvement of foot-fault (r = 0.70, P < 0.01).

CONCLUSIONMCI-186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Bone Marrow Cells ; cytology ; physiology ; Brain Ischemia ; drug therapy ; metabolism ; therapy ; Chemokine CXCL12 ; metabolism ; Disease Models, Animal ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; therapy ; Male ; Mesenchymal Stromal Cells ; physiology ; Neurogenesis ; physiology ; Rats ; Rats, Sprague-Dawley ; Stroke ; drug therapy ; metabolism ; therapy

OBJECTIVETo explore the pattern of variations in middle cerebral artery peak systolic velocity (MCA PSV) and cardiothoracic ratio (CTR) during early pregnancy, establish their reference ranges and explore their correlation with the crown-rump length (CRL).

METHODSA total of 522 pregnant women with normal findings in antenatal examinations underwent routine color Doppler ultrasound examination to collect the data of MCA PSV, CTR and CRL. The reference ranges of MCA PSV and CTR for different CRL levels were established, and the correlation of MCA PSV and CTR with CRL was analyzed.

RESULTSDuring the first trimester, MCA PSV and CRL showed a moderate positive correlation with a correlation coefficient of 0.426 (P<0.001), while CTR and CRL showed no significant correlation (0.168, P<0.001). The reference range of MCA PSV was 14.35 (14.08-14.62) cm/s and that of CTR was 0.34 (0.33-0.34) during early pregnancy.

CONCLUSIONColor Doppler ultrasound is a safe and feasible modality to assess fetal MCA PSV and CTR for detecting fetal growth abnormalities in early pregnancy. The established reference ranges of MCA PSV and CTR offer a clinical theoretical basis for detecting α-thalassemia in early pregnancy.

Blood Flow Velocity ; Crown-Rump Length ; Female ; Fetal Diseases ; diagnostic imaging ; Humans ; Middle Cerebral Artery ; physiology ; Pregnancy ; Pregnancy Trimester, First ; Reference Values ; Systole ; Ultrasonography, Doppler, Color ; Ultrasonography, Prenatal

PURPOSE: Lacunar stroke, in the context of small vessel disease, is a type of cerebral infarction caused by occlusion of a penetrating artery. Pulsatility index (PI) is an easily measurable parameter in Transcranial Doppler ultrasound (TCD) study. PI reflects distal cerebral vascular resistance and has been interpreted as a surrogate marker of small vessel disease. We hypothesized that an increased PI, a marker of small vessel disease, might be associated with a larger infarct volume in acute lacunar stroke. MATERIALS AND METHODS: This study included 64 patients with acute lacunar stroke who underwent TCD and brain MRI. We evaluated the association between the mean PI value of bilateral middle cerebral arteries and infarct volume on diffusion-weighted MRI using univariate and multivariate linear regression. RESULTS: The mean infarct volume and PI were 482.18±406.40 mm3 and 0.86±0.18, respectively. On univariate linear regression, there was a significant positive association between PI and infarct volume (p=0.001). In the multivariate model, a single standard deviation increase of PI (per 0.18) was associated with an increase of 139.05 mm3 in infarct volume (95% confidence interval, 21.25 to 256.85; p=0.022). CONCLUSION: We demonstrated that PI was an independent determinant of infarct volume in acute lacunar stroke. The PI value measured in acute stroke may be a surrogate marker of the extent of ischemic injury.
Aged ; Cerebral Infarction/*diagnostic imaging/*physiopathology ; *Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Middle Cerebral Artery ; Pulsatile Flow/physiology ; Retrospective Studies ; Stroke, Lacunar/*diagnostic imaging/*physiopathology ; *Ultrasonography, Doppler, Transcranial ; Vascular Resistance/physiology

OBJECTIVETo observe whether adenosine Al receptor (Al R) mediated neuroprotection of Shenmai Injection (SI) on rat cerebral ischemia/reperfusion (I/R) injury.

METHODSThe focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO). Totally 60 successfully modeled rats was divided into 5 groups according to randomized block principle, i.e., the model group, the SI group, the SI + AlR antagonist (1,3-dipropyl-8-cyclopentylxanthine, DPCPX) group, the AlR antagonist control group, and the dimethyl sulfoxide (DMSO) control group, 12 in each group. Besides, a sham-operation group was set up (n =12). SI at 15 mL/kg was peritoneally injected to mice in the SI group immediately after cerebral I/R. Equal volume of normal saline was injected to mice in the model group and the sham-operation group. DPCPX at 1 mg/mL was peritoneally injected to mice in the Al R antagonist control group 30 min before peritoneal injecting SI. DPCPX at 1 mg/kg and DMSO at 1 mL/kg were peritoneally injected to mice in the AlR antagonist control group and the DMSO control group 30 min immediately before cerebral I/R. Rats' neurobehavioral scores were assessed after 24 h reperfusion. The volume of cerebral infarction and Bcl-2 protein expression of cerebral infarction penumbra were also detected. Results Compared with the sham-operation group, neurobehavioral scores, the volume of cerebral infarction, and Bcl-2 protein expression increased (all P <0. 05). Compared with the model group, neurobehavioral scores and the volume of cerebral infarction obviously decreased, but Bcl-2 protein expression increased in the SI group (all P <0. 05). Compared with the SI group, neurobehavioral scores increased, the volume of cerebral infarction was obviously enlarged, and Bcl-2 protein expression was obviously reduced in the A1R antagonist control group (all P <0. 05).

CONCLUSIONSSI's neurobehavioral scores could be partially reversed in the Al R antagonist control group, the volume of cerebral infarction and Bcl-2 protein expression improved. AlR might possibly meditate neuroprotection of SI on MACO mire

Adenosine ; Animals ; Brain Ischemia ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Infarction, Middle Cerebral Artery ; Mice ; Neuroprotection ; physiology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptor, Adenosine A1 ; metabolism ; Reperfusion Injury ; drug therapy ; Xanthines

This study was aimed to investigate the changes of the hypothalamic-pituitary-adrenal axis (HPAA) activity and the cytokines system in the hypothalamus of the depressive rats which were exposed to chronic unpredictable mild stressors (CUMS) after middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and Western blot, mRNA and/or protein expressions of corticotropin releasing factor (CRF), tumor necrosis factors-α (TNF-α), suppressor of cytokines signaling 3 (SOCS3), phosphorylation of signal transducers and activators of transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results showed that, compared with control group, CUMS+MCAO group exhibited increased mRNA levels of CRF, TNF-α, SOCS3, as well as up-regulated CRF, TNF-α, SOCS3 and pSTAT3 protein expressions. Furthermore, there were correlations between CRF and TNF-α, TNF-α and SOCS3, SOCS3 and pSTAT3, respectively. These observations indicated the CRF system was activated in the post stroke depression (PSD) status. The TNF-α and its signaling pathway, STAT3/SOCS3, were up-regulated in mRNA and protein levels. In conclusion, this study presents the evidence which supports the hypothesis of signaling cross-talk between the CRF system and TNF-α signaling pathway after ischemic stroke and CUMS.
Animals ; Hypothalamo-Hypophyseal System ; physiology ; Hypothalamus ; physiology ; Infarction, Middle Cerebral Artery ; Phosphorylation ; Pituitary-Adrenal System ; physiology ; Rats ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Up-Regulation

OBJECTIVETo observe the effect and mechanism of Huatuo Zaizao extractum (HTZZ) on focal ischemia/reperfusion (I/R) blood-brain barrier injury induced by middle cerebral artery occlusion.

METHODSixty healthy male adult Sprague-Dawley rats was randomly divided into the sham operation group, the MCAO model group, the Tanakan (20 mg x kg(-1)) group, and high, middle and low-dose HTZZ groups (5, 2.5, 1.25 g x kg(-1)), with 10 in each group and single-dose duodenal administration. Middle cerebral artery occlusion was adopted to establish the rat focal I/R model. After ischemia for 90 min and reperfusion for 24 h, the pathological injury at the ischemia side was observed by HE staining. The blood-brain barrier structure was observed under transmission electron microscope. Expressions of G protein-coupled receptor kinases 2 (GRK2), matrix metalloproteinases 2 (MMP-2) and MMP-9 were detected by western blotting technique.

RESULTAfter 90 min MCAO/24 h reperfusion, penumbra cerebral cortical micro-vessels showed edema, mitochondrial injury, vacuolation, membrane injury and reduction. Along with the changes, sub-cells of G protein-coupled receptor kinase 2 (GRK2) in cortical penumbra brain tissues transferred from cytoplasm to membrane, with increase in expressions of MMP-2 and MMP-9. HTZZ could effectively recover cerebral micro-vascular endothelial edemaand blood-brain barrier ultrastructure injury induced by I/R, reduce expression of functional (membrane coupling) GRK2, and inhibit expressions of MMP-2 and MMP-9.

CONCLUSIONCell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.

Animals ; Behavior, Animal ; drug effects ; physiology ; Blood-Brain Barrier ; drug effects ; injuries ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; G-Protein-Coupled Receptor Kinase 2 ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Infarction, Middle Cerebral Artery ; complications ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Microvessels ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; metabolism ; physiopathology

OBJECTIVE: To investigate the diagnostic value of transcranial Doppler ultrasound in early stage cerebral arteriosclerosis. METHODS: We selected 50 patients with early cerebral arteriosclerosis as the disease group. At the same time we selected another 50 patients as a control group with no significant symptoms in the nervous system. By 2 MHz pulse Doppler probe through double-temporal windows and pillow windows Basilar artery (BA), the bilateral middle cerebral artery (MCA) was detected. In the TCD spectrum, we selected the spectrum of a single-family cardiac cycle, identified the starting point (ts), pulse-incisure point (ti), end point (te), and the peak velocity (tp), measured the time of the spectrum starting point to the peak velocity (Tp) and calculated the time required for the peak velocity in the share of ventricular systolic (Tp/Ti), the time required for the peak velocity in the share of the whole cardiac cycle (Tp/T). Tp, Tp/Ti and Tp/T were respectively named as time to peak velocity (TPV), peak-time index-1 (PTI-1) and peak-time index-2 (PTI-2). All data were analyzed by SPSS13.0. RESULTS: There was no significant difference in blood vessel velocity, PI, RI and S/D of BA and RMCA (P>0.05) between the control group and the disease group. Compared with the control group, TPV of the BA, LMCA and RMCA significantly extended, PTI-1 and PTI-2 of BA, LMCA and RMCA increased significantly in the disease group (P<0.01). In the disease group, there was no significant correlation between peak time index and PI, S/D (P>0.05). CONCLUSION TPV, PTI-1 and PTI-2 are sensitive indicators of early stage cerebral arteriosclerosis.
Adult ; Basilar Artery ; diagnostic imaging ; Blood Flow Velocity ; physiology ; Case-Control Studies ; Female ; Humans ; Intracranial Arteriosclerosis ; diagnostic imaging ; Male ; Middle Aged ; Middle Cerebral Artery ; diagnostic imaging ; Ultrasonography, Doppler, Transcranial

OBJECTIVETo observe the effect of willed movement therapy on the expression of neurotrophin 3 (NT-3) and growth associated protein 43 (GAP-43) in rats with cerebral ischemia-reperfusion (IR) and investigate the neuroprotective mechanism of willed movement therapy in nerve regeneration and repair.

METHODSCerebral IR model was established by middle cerebral artery occlusion (MCAO) in SD rats. The rats were randomly divided into MCAO group, environment modification group (EM group) and willed movement therapy group (WM group). The rats were evaluated for neurological deficits and decapitated on days 3, 7 and 15 after the reperfusion to examine the expressions of NT-3 and GAP-43 in the ischemic brain tissues by immunohistochemistry.

RESULTSCompared with MCAO and EM groups, the rats in WM group showed significantly lowered grade of neurological deficits (P<0.05) at 15 days and significantly increased the expressions of NT-3 and GAP-43 (P<0.05) at 7 and 15 days after the reperfusion. No significant difference was found in the expression of NT-3 and GAP-43 between MCAO and EM groups (P>0.05). The expression of NT-3 was positively correlated to that of GAP-43 in the ischemic tissues.

CONCLUSIONSWilled movement therapy increases the expression of NT-3 and GAP-43 in the ischemic brain area in rats with cerebral ischemia-reperfusion, which is probably related to nerve regeneration and repair.

Animals ; Brain Ischemia ; metabolism ; therapy ; Exercise Therapy ; methods ; GAP-43 Protein ; metabolism ; Infarction, Middle Cerebral Artery ; metabolism ; therapy ; Male ; Movement ; physiology ; Nerve Regeneration ; Neuronal Plasticity ; physiology ; Neurotrophin 3 ; metabolism ; Physical Exertion ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; therapy