Minocycline improves learning and memory functions in ischemic stroke rats via reduction of cerebral ischemia-induced neuroinflammation and apoptosis

Purpose: To study the effect minocycline on learning and memory functions in ischemic stroke rats, and the underlying mechanism. Methods: 60 adult male SD rats were randomly divided into control group, ischemic brain damage (6 and 24 h MACO) groups; and 6 and 24 h minocycline groups, with 12 rats in each group. The volume of cerebral infarction, neuronal cell apoptosis, NF-κB protein expression, learning and memory ability, and the number of Iba-1+CD206-positive cells, and CD206/CD68 mRNA expressions in sham group, 6 h MACO group and 6 h minocycline group were determined and compared. Results: The number of iba-1 +CD206-positive cells, expression level of CD206 mRNA, frequency of platform crossing, and percentage of third quadrant route in 6 h minocycline group were significantly higher than the corresponding values in 6 h MACO group. However, the cerebral infarction volume, number of Nini-positive cells, and the NF- B protein expression levels were markedly reduced, relative to corresponding values in 6 h MACO rats. The number of iba-1+CD206-positive cells was significantly lower in 6 h MACO rats than in sham rats, while the expression level of CD68 mRNA was significantly higher (p < 0.05). The number of TUNEL-positive cells in 6 and 24 h minocycline groups were markedly lower than that in 6 h MACO group (p < 0.05). Conclusion: Minocycline improves learning and memory of ischemic stroke rats by relieving the neuroinflammation induced by cerebral ischemia and cell apoptosis. Thus, the compound can be further developed for management learning and memory deficits in stroke patients.

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Panax Notoginseng Burk Attenuates Impairment of Learning and Memory Functions and Increases ED1, BDNF and β-Secretase Immunoreactive Cells in Chronic Stage Ischemia-Reperfusion Injured Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x08006156 ◽

2008 ◽

Vol 36 (04) ◽

pp. 685-693 ◽

Cited By ~ 22

Author(s):

Chin-Min Chuang ◽

Ching-Liang Hsieh ◽

Hui-Yi Lin ◽

Jaung-Geng Lin

Keyword(s):

Cerebral Infarction ◽

Learning And Memory ◽

Radial Maze ◽

Ischemia Reperfusion ◽

Panax Notoginseng ◽

Cerebral Infarct ◽

Control Group ◽

Memory Functions ◽

Activated Microglia ◽

Maze Test

Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as well as learning and memory functions. The purpose of the present study was to investigate the effect of PN on learning and memory functions in chronic cerebral infarct rats. A cerebral infarct animal model was established by blocking the blood flow of both common carotid arteries and right middle cerebral artery for 90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally 3 days per week for 4 weeks, whereas the control group provided bait and water only. The learning and memory functions were estimated by measuring how successful rats were able to negotiate an 8-arm radial maze test; the test was performed after operation once a week for 4 weeks. Finally, the rats were sacrificed and their brains were removed. The brains were sectioned and analyzed for ED1, glial fibrillary acid protein (GFAP), nuclear factor-κB, and brain derivative neurotrophin factor (BDNF) and β-secretase by immunostaining. Cerebral infarct rats given PN were able to successfully navigate the 8-arm radial maze test four weeks after cerebral infarction. PN also increased ED1, BDNF and β-secretase immunoreactive cells, but did not increase GFAP and NF-κB immunoreactive cells. PN attenuated the reduction in learning and memory functions induced by cerebral infarction in cerebral ischemia-reperfusion injured rats; it also increased the amount of activated microglia and BDNF. These data suggest that the effect of PN, at least in part, is closely related to the increase in BDNF that was generated by activated microglia. The effect that PN has on astrocytes, NF-κB and β-secreatase immunoreactive cells requires further study.

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Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200219121600 ◽

2020 ◽

Vol 23 (3) ◽

pp. 214-224 ◽

Cited By ~ 1

Author(s):

Esra Cakir ◽

Ufuk Cakir ◽

Cuneyt Tayman ◽

Tugba Taskin Turkmenoglu ◽

Ataman Gonel ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Brain Damage ◽

Neurological Deficit ◽

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Degradation Products ◽

Ischemia Reperfusion ◽

Control Group ◽

Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

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MiR-206 regulates the progression of osteoporosis via targeting HDAC4

European Journal of Medical Research ◽

10.1186/s40001-021-00480-3 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Zhiyuan Lu ◽

Dawei Wang ◽

Xuming Wang ◽

Jilong Zou ◽

Jiabing Sun ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Diagnostic Value ◽

Expression Level ◽

Luciferase Reporter ◽

Control Group ◽

Luciferase Reporter Gene ◽

Mineral Density ◽

Gene Assay

Abstract Background More and more studies have confirmed that miRNAs play an important role in maintaining bone remodeling and bone metabolism. This study investigated the expression level of miR-206 in the serum of osteoporosis (OP) patients and explored the effect and mechanism of miR-206 on the occurrence and development of osteoporosis. Methods 120 postmenopausal women were recruited, including 63 cases with OP and 57 women without OP. The levels of miR-206 were determined by qRT-PCR technology. Spearman correlation coefficient was used to evaluate the correlation of miR-206 with bone mineral density (BMD). An ROC curve was used to evaluate the diagnostic value of miR-206 in osteoporosis. The effects of miR-206 on cell proliferation and cell apoptosis of hFOBs were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter gene assay was used to confirm the interaction of miR-206 and the 3′UTR of HDAC4. Results Serum miR-206 had low expression level in osteoporosis patient group compared with control group. The expression level of serum miR-206 had diagnostic value for osteoporosis, and the serum miR-206 levels were positively correlated with BMD. The down-regulated miR-206 could inhibit cell proliferation and promote cell apoptosis. Luciferase analysis indicated that HDAC4 was the target gene of miR-206. Conclusions MiR-206 could be used as a new potential diagnostic biomarker for osteoporosis, and in in vitro cell experiments, miR-206 may regulate osteoblast cell proliferation and apoptosis by targeting HDAC4.

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Abstract WP319: miRNA Screening of Natural Killer Cell Identifies miR-1224 as a Post-Transcriptional Regulator of NK Cell Function After Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wp319 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yan Feng ◽

Hui Zhao ◽

Fu-Dong Shi ◽

Weina Jin

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Nk Cells ◽

Expression Profile ◽

Mirna Expression ◽

Cell Function ◽

Nk Cell ◽

Killer Cell ◽

Mirna Expression Profile ◽

Control Group

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.

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Piceatannol Ameliorates Hepatic Oxidative Damage and Mitochondrial Dysfunction of Weaned Piglets Challenged with Diquat

Animals ◽

10.3390/ani10071239 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1239

Author(s):

Peilu Jia ◽

Shuli Ji ◽

Hao Zhang ◽

Yanan Chen ◽

Tian Wang

Keyword(s):

Oxidative Damage ◽

Protein Expression ◽

Complex I ◽

Sirtuin 1 ◽

Expression Level ◽

Control Group ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Protein Expression Level ◽

Atp Production

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis.

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Proteomic Assessment of iTRAQ-Based NaoMaiTong in the Treatment of Ischemic Stroke in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5107198 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Kening Li ◽

Minghua Xian ◽

Chi Chen ◽

Shengwang Liang ◽

Lei Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Western Blot ◽

Stress Responses ◽

Neuronal Damage ◽

Interaction Analysis ◽

Protective Effects ◽

Cellular Mechanisms ◽

Altered Expression

Background. NaoMaiTong (NMT) is widely used in the treatment of cerebral ischemia but the molecular details of its beneficial effects remain poorly characterized. Materials and Methods. In this study, we used iTRAQ using 2D LC-MS/MS technology to investigate the cellular mechanisms governing the protective effects of NMT. The transient middle cerebral artery occlusion (MCAO) rat model was established and evaluated. The degree of cerebral ischemia was assessed through scoring for nerve injury symptoms and through the assessment of the areas of cerebral infarction. Brain tissues were subjected to analysis by iTRAQ. High-pH HPLC and RSLC-MS/MS analysis were performed to detect differentially expressed proteins (DEPs) between the treatment groups (Sham, MCAO, and NMT). Bioinformatics were employed for data analysis and DEPs were validated by western blot. Results. The results showed that NMT offers protection to the neurological damage caused by MCAO and was found to reduce the areas of cerebral infarction. We detected 3216 DEPs via mass spectrometry. Of these proteins, 21 displayed altered expression following NMT intervention. These included DEPs involved in translation, cell cycle regulation, cellular nitrogen metabolism, and stress responses. Pathway analysis revealed seven key DEPs that were enriched in ribosomal synthesis pathways, tight junction formation, and regulation of the actin cytoskeleton. According to protein-protein interaction analysis, RPL17, Tuba, and Rac1 were affected by NMT treatment, which was validated by western blot analysis. Discussion. We therefore identify new pharmacodynamic mechanisms of NMT for the prevention and treatment of ischemic stroke. These DEPs reveal new targets to prevent ischemic stroke induced neuronal damage.

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Passive Movement Improves the Learning and Memory Function of Rats with Cerebral Infarction by Inhibiting Neuron Cell Apoptosis

Molecular Neurobiology ◽

10.1007/s12035-013-8512-9 ◽

2013 ◽

Vol 49 (1) ◽

pp. 216-221 ◽

Cited By ~ 6

Author(s):

Man Li ◽

Jun Peng ◽

Meng-Die Wang ◽

Yan-Ling Song ◽

Yuan-Wu Mei ◽

...

Keyword(s):

Cerebral Infarction ◽

Learning And Memory ◽

Cell Apoptosis ◽

Memory Function ◽

Passive Movement

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The effect of miR-23b-3p on growth hormone in pituitary cells of Yanbian yellow cattle

10.21203/rs.3.rs-18322/v1 ◽

2020 ◽

Author(s):

Jiuxiu Ji ◽

Angang Lou ◽

Rui Zhang ◽

Taihua Jin ◽

Siyu Xiang ◽

...

Keyword(s):

Protein Expression ◽

Expression Level ◽

Luciferase Reporter ◽

Control Group ◽

Pituitary Cells ◽

Mrna Transcription ◽

Luciferase Reporter Gene ◽

Protein Expression Level ◽

Yellow Cattle ◽

Reporter Gene System

Abstract Background There is a relationship between miR-23b-3p and GH in pituitary of Yanbian yellow cattle. However, the specific mechanism of the effect of miR-23b-3p on GH in pituitary of Yanbian yellow cattle is still unclear.This study aimed to evaluate the effect of miR-23b-3p on growth hormone (GH) in pituitary cells of Yanbian yellow cattle. Methods The primary culture of Yanbian yellow cattle pituitary cells was carried out, and mimics (miR-23b-3p-mi group), mimics reference substance (NC group), inhibitor (miR-23b-3p-in group) and inhibitor reference substance (iNC group) of miR-23b-3p were transfected into the established pituitary primary cells. After 48 h, the cells were collected and the total RNA and protein were extracted.The mRNA transcription and protein expression level of GH and miR-23b-3p target genes were detected by real time fluorescence quantitative PCR (qPCR) and Western blot, respectively. The target relationship of miR-23b-3p was validated by double luciferase reporter gene system. Results Compared with the NC control group, GH mRNA transcription and protein expression level in pituitary cells of Yanbian yellow cattle was significantly decreased by adding miR-23b-3p minics ( P <0.01), while compared with the iNC control group, GH mRNA transcription and protein expression level were significantly increased by adding miR-23b-3p inhibitor( P <0.05). The result of bioinformatics analysis and double luciferase reporter gene system validation proved that miR-23b-3p targeted 3'UTR of pituitary specific transcription factor 1 (POU1F1). Compared with the NC control group, POU1F1 mRNA transcription and protein expression level were significantly inhibited by the addition of miR-23b-3p minics ( P <0.01), while compared with the iNC control group, POU1F1 mRNA transcription and protein expression level were significantly increased by the addition of miR-23b-3p inhibitor ( P <0.01). Conclusions miR-23b-3p could regulate GH in pituitary cells by regulating POU1F1 gene.

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Notch Signaling Pathway Is Involved in bFGF-Induced Corneal Lymphangiogenesis and Hemangiogenesis

Journal of Ophthalmology ◽

10.1155/2019/9613923 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Fang Xie ◽

Xue Zhang ◽

Wenting Luo ◽

Hongyan Ge ◽

Dawei Sun ◽

...

Keyword(s):

Growth Factor ◽

Protein Expression ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Expression Level ◽

Control Group ◽

Fluorescence Signal ◽

Mrna And Protein Expression ◽

Corneal Lymphangiogenesis

Background. Notch/Dll4 involvement in cornea neovascularization (CRNV) and lymphangiogenesis is unclear. This study aimed to explore the role of notch signaling in basic fibroblast growth factor- (bFGF-) induced corneal lymphangiogenesis and hemangiogenesis. Methods. Corneal stroma of C57BL/6 mice was implanted with bFGF- or phosphate-buffered saline- (PBS-) soaked pellets. Corneal lymphangiogenesis and neovascularization were evaluated by immunofluorescence. Vascular endothelial growth factor-A (VEGF-A), Delta-like ligand 4 (Dll4), and Notch1 mRNA and protein expression were examined on days 1, 3, 7, and 14 by real-time polymerase chain reaction and western blot. Corneal cells were treated with ranibizumab, dexamethasone, and γ-secretase inhibitor (GSI). Microspheres were used to evaluate corneal hemangiogenesis in vivo. Results. Corneal hemangiogenesis reached its peak on day 7 after bFGF implantation, and corneal lymphangiogenesis was significantly higher on day 7 and 14, compared with PBS. mRNA and protein expression of VEGF-A, Dll4, and Notch1 were higher in bFGF-induced animal models compared with controls. Corneal hemangiogenesis and lymphangiogenesis decreased after 7 days of ranibizumab or dexamethasone treatment. After adding GSI for 24 h in bFGF-induced cells, the expression of Notch1 and Dll4 were downregulated compared with that in the control group whereas the expression level of VEGF-A was upregulated. Fluorescent particle number was higher in the GSI group. Ranibizumab and dexamethasone decreased the fluorescence signal. Conclusion. The notch signaling pathway plays a role in regulating VEGF expression, affecting corneal lymphangiogenesis and hemangiogenesis in mice. The molecular imaging probe technique can visualize the changes in the VEGF-A expression level of corneal limbus hemangiogenesis.

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Abstract W P86: Photo-stimulation of the Striatum Promotes Functional Recovery and Neurogenesis after Focal Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.wp86 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Mingke Song ◽

Osama Mohamad ◽

Xiaohuan Gu ◽

Shipeng Wei ◽

Ling Wei ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Functional Recovery ◽

Focal Cerebral Ischemia ◽

Blue Laser ◽

Control Group ◽

Stroke Treatment ◽

Adhesive Removal ◽

The Brain ◽

Stimulation Of

Introduction and Purpose: The striatum region of the brain supports self-repair process after experimental cerebral ischemia. Optogenetics is a temporally and spatially precise method to manipulate targeted neuronal populations. We tested whether optogenetic technique can be translated into stroke treatment by photo-stimulation of the striatum after focal cerebral ischemia. Methods: Adult male channelrhodopsin-2 (ChR2) transgenic mice were utilized, taking the advantage of that the cation channel ChR2 is abundantly expressed in the striatum. Before stroke, mice were trained 5 times per day for 3 days with a modified adhesive removal test. Mice were then subjected to the ischemic insult targeting the right sensorimotor (barrel) cortex. Four days after stroke, optical fibers were implanted into the striatum and fixed with a cannula on the skull. In control group, stoke mice received optical fiber implantation but without photo-stimulation. In treatment group, daily photo-stimulation pulses (473 nm blue laser) were started at 5 days after stroke and sustained for 8 days. The adhesive removal test on forepaws was performed 3, 10, 17, 24, and 31 days after stroke. Results: The impaired forepaw sensorimotor function in these two groups progressively recovered over the timeline. Stroke mice treated with photo-stimulation showed significantly better recovery assessed 31 days after stroke compared to stroke control. Our study also shows that the activity of neurogenesis in the brain was augmented by photo-stimulation, which may be responsible for enhanced functional recovery. Conclusions: Optogenetic stimulation of the striatum promotes functional recovery and neurogenesis after focal ischemic stroke.

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