Reasearch progress of signaling pathways and related therapies in neurogenesis after ischemic stroke
CHEN Yanxi1 XU Zhidong2 SUN Fangling1 WANG Wen1
1.Experimental Animal Center, Xuanwu Hospital, Capital Medical University Beijing Municipal Geriatric Medical Research Center, Beijing 100053, China; 2.School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Hebei Province, Shijiazhuang 050018, China
Abstract：Ischemic stroke is a cerebrovascular disease that seriously reduces people’s quality of life. The effective therapeutic drug of this disease, Alteplase, has a narrow thrombolytic time window, which limits the application of patients. Wnt/β-catenin, Notch, PI3K/Akt, MAPK, and Eph-ephrin pathways play important roles in the development of central nervous system and are involved in cell growth, migration, and adhesion. Since adult nerve cells growth have been stopped, reactivation of these pathways may bring hope for endogenous regeneration and repair of brain injury. Finding mechanisms and drugs targeting these pathways involved in neurogenesis will be beneficial to stroke rehabilitation. This article reviews the key processes and drug development of these pathways involved in neurogenesis.
陈彦熹1 徐志栋2 孙芳玲1 王文1. 缺血性脑卒中后神经发生相关信号通路及药物研究进展[J]. 中国医药导报, 2023, 20(21): 35-39.
CHEN Yanxi1 XU Zhidong2 SUN Fangling1 WANG Wen1. Reasearch progress of signaling pathways and related therapies in neurogenesis after ischemic stroke. 中国医药导报, 2023, 20(21): 35-39.
[1] Khatri P. Intravenous thrombolysis before thrombectomy for acute ischaemic stroke [J]. Lancet，2022，400（10346）：76-78.
[2] Li W，Ye A，Ao L，et al. Protective Mechanism and Treatment of Neurogenesis in Cerebral Ischemia [J]. Neurochem Res，2020，45（10）：2258-2277.
[3] Jurkowski MP，Bettio L，K Woo E，et al. Beyond the Hippocampus and the SVZ：Adult Neurogenesis throughout the Brain [J]. Front Cell Neurosci，2020，14：576444.
[4] Zhan L，Liu D，Wen H，et al. Hypoxic Postconditioning Activates the Wnt/β-catenin Pathway and Protects against Transient Global Cerebral Ischemia through Dkk1 Inhibition and GSK-3β Inactivation [J]. FASEB J，2019，33（8）：9291- 9307.
[5] Kriska J， Janeckova L， Kirdajova D，et al. Wnt/β-catenin Sig- naling Promotes Differentiation of Ischemia-activated Adult Neural Stem/Progenitor Cells to Neuronal Precursors [J]. Front Neurosci，2021，15：628983.
[6] Sun FL，Wang W，Zuo W，et al. Promoting Neurogenesis via Wnt/β-catenin Signaling Pathway Accounts for the Neurorestorative Effects of Morroniside against Cerebral Ischemia Injury [J]. Eur J Pharmacol，2014，738：214-221.
[7] Zhang S，Kong DW，Ma GD，et al. Long-term Administration of Salvianolic Acid A Promotes Endogenous Neurogenesis in Ischemic Stroke Rats through Activating Wnt3a/GSK3β/ β-catenin Signaling Pathway [J]. Acta Pharmacol Sin，2022， 43（9）：2212-2225.
[8] Chen YA，Tsai YC，Chen YD，et al. Intraventricular Medium B Treatment Benefits an Ischemic Stroke Rodent Model via Enhancement of Neurogenesis and Anti-apoptosis [J]. Sci Rep， 2020，10（1）：6596.
[9] Yang X，Song D，Chen L，et al. Curcumin Promotes Neurogenesis of Hippocampal Dentate Gyrus via Wnt/β-catenin Signal Pathway Following Cerebral Ischemia in Mice [J]. Brain Res，2021，1751：147197.
[10] Yan Y，Kong L，Xia Y，et al. Osthole Promotes Endogenous Neural Stem Cell Proliferation and Improved Neurological Function through Notch Signaling Pathway in Mice Acute Mechanical Brain Injury [J]. Brain Behav Immun，2018，67： 118-129.
[11] Tian H，Li X，Tang Q，et al. Yi-nao-jie-yu Prescription Exerts a Positive Effect on Neurogenesis by Regulating Notch Signals in the Hippocampus of Post-stroke Depression Rats [J]. Front Psychiatry，2018，9：483.
[12] Ribeiro TN，Delgado-García LM，Porcionatto MA. Notch1 and Galectin-3 Modulate Cortical Reactive Astrocyte Response after Brain Injury [J]. Front Cell Dev Biol，2021，9：649854.
[13] Liu B，Zhang Q，Ke C，et al. Ginseng-Angelica-Sansheng- Pulvis Boosts Neurogenesis Against Focal Cerebral Ischemia-Induced Neurological Deficiency [J]. Front Neurosci，2019，13：515.
[14] An B，Ma Y，Xu Y，et al. Crocin Regulates the Proliferation and Migration of Neural Stem Cells after Cerebral Ischemia by Activating the Notch1 Pathway [J]. Folia Neuropathol，2020，58（3）：201-212.
[15] Gao H，Huang N，Wang W，et al. Astragalus Flavone Induces Proliferation and Differentiation of Neural Stem Cells in a Cerebral Infarction Model [J]. Med Sci Monit，2022，28： e933830.
[16] Zhou Z，Dun L，Wei B，et al. Musk Ketone Induces Neural Stem Cell Proliferation and Differentiation in Cerebral Ischemia via Activation of the PI3K/Akt Signaling Pathway [J]. Neuroscience，2020，435：1-9.
[17] Kisoh K，Hayashi H，Arai M，et al. Possible Involvement of PI3-K/Akt-Dependent GSK-3β Signaling in Proliferation of Neural Progenitor Cells after Hypoxic Exposure [J]. Mol Neurobiol，2019，56（3）：1946-1956.
[18] Wang Y，Liu X，Hu T，et al. Astragalus Saponins Improves Stroke by Promoting the Proliferation of Neural Stem Cells through Phosphorylation of Akt [J]. J Ethnopharmacol，2021， 277：114224.
[19] Du Q，Deng R，Li W，et al. Baoyuan Capsule Promotes Neurogenesis and Neurological Functional Recovery Through Improving Mitochondrial Function and Modulating PI3K/ Akt Signaling Pathway [J]. Phytomedicine，2021，93：153795.
[20] Choi NY，Kim JY，Hwang M，et al. Atorvastatin Rejuvenates Neural Stem Cells Injured by Oxygen-Glucose Deprivation and Induces Neuronal Differentiation Through Activating the PI3K/Akt and ERK Pathways [J]. Mol Neurobiol，2019，56（4）：2964-2977.
[21] Gudasheva TA，Povarnina PY，Volkova AA，et al. A Nerve Growth Factor Dipeptide Mimetic Stimulates Neurogenesis and Synaptogenesis in the Hippocampus and Striatum of Adult Rats with Focal Cerebral Ischemia [J]. Acta Naturae，2019，11（3）：31-37.
[22] Liu W，Wu W，Lin G，et al. Physical Exercise Promotes Proliferation and Differentiation of Endogenous Neural Stem Cells via ERK in Rats with Cerebral Infarction [J]. Mol Med Rep，2018，18（2）：1455-1464.
[23] Park HJ，Choi JH，Nam MH，et al. Induced Neurodifferentiation of hBM-MSCs Through Activation of the ERK/ CREB Pathway via Pulsed Electromagnetic Fields and Physical Stimulation Promotes Neurogenesis in Cerebral Ischemic Models [J]. Int J Mol Sci，2022，23（3）：1177.
[24] Cheng CY，Huang HC，Kao ST，et al. Angelica Sinensis Extract Promotes Neuronal Survival by Enhancing p38 MAPK-mediated Hippocampal Neurogenesis and Dendritic Growth in the Chronic Phase of Transient Global Cerebral Ischemia in Rats [J]. J Ethnopharmacol，2021，278：114301.
[25] Chen X，Wu H，Chen H，et al. Astragaloside Ⅵ Promotes Neural Stem Cell Proliferation and Enhances Neurological Function Recovery in Transient Cerebral Ischemic Injury via Activating EGFR/MAPK Signaling Cascades [J]. Mol Neurobiol，2019，56（4）：3053-3067.
[26] Gudasheva TA，Povarnina PY，Antipova TA，et al. Neuroregenerative Activity of the Dipeptide Mimetic of Brain- derived Neurotrophic Factor GSB-106 Under Experimental Ischemic Stroke[J]. CNS Neurol Disord Drug Targets，2021， 20（10）：954.
[27] Liu Y，Ren J，Kang M，et al. Progranulin Promotes Functional Recovery and Neurogenesis in the Subventricular Zone of Adult Mice after Cerebral Ischemia [J]. Brain Res，2021，1757：147312.
[28] Doeppner TR，Bretschneider E，Doehring M，et al. Enhancement of Endogenous Neurogenesis in Ephrin-B3 Deficient Mice after Transient Focal Cerebral Ischemia [J]. Acta Neu- ropathol，2011，122（4）：429-42.
[29] Kischel A，Audouard C，Fawal MA，et al. Ephrin-B2 Paces Neuronal Production in the Developing Neocortex [J]. BMC Dev Biol，2020，20（1）：12.
[30] Yu Z，Li W，Lan J，et al. EphrinB2-EphB2 Signaling for Dendrite Protection after Neuronal Ischemia in Vivo and Oxygen-glucose Deprivation in Vitro [J]. J Cereb Blood Flow Metab，2021，41（7）：1744-1755.
[31] Liu T，Zeng X，Sun F，et al. EphB4 Regulates Self-Renewal，Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro [J]. Cell Physiol Bioc- hem，2017，41（2）：819-834.
[32] Wang J，Zhang Z，Fu S，et al. Overexpression of EphB4 Promotes Neurogenesis，but Inhibits Neuroinflammation in Mice with Acute Ischemic Stroke [J]. Mol Med Rep，2021， 24（5）：756.
[33] Cai J，Wu C，Tang C，et al. The influence of Tongqiao Hua- shuan Decoction on the Expression of VEGF and EphB2 in MCAO Model Rats [J]. Ann Palliat Med，2019，8（5）：667- 675.
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