Effects of gastrodin on astrocyte phenotype and the receptor of advanced glycation endproducts expression after hypoxic-ischemic brain damage in neonatal rats

WANG Peng-Xiang; REN Xue-Qi; ZUO Han-Jun; WAN Cheng; SHI Jin-Sha; SHI Hao-Long; ZHAO Min; LI Juan-Juan

doi:10.16098/j.issn.0529-1356.2024.06.004

PDF(13788 KB)

Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (6) : 677-684. DOI: 10.16098/j.issn.0529-1356.2024.06.004

Effects of gastrodin on astrocyte phenotype and the receptor of advanced glycation endproducts expression after hypoxic-ischemic brain damage in neonatal rats

WANG Peng-xiang¹ REN Xue-qi¹ ZUO Han-jun¹ WAN Cheng² SHI Jin-sha¹ SHI Hao-long¹ZHAO Min^1* LI Juan-juan^1*

Author information +

History +

Abstract

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts (RAGE) of astrocytes after hypoxicischemic brain damage(HIBD) in neonatal rats and the effects of gastrodin (GAS) intervention on them. Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group, HIBD group and HIBD+GAS group(100 mg/kg), and the expressions of A1 type astrocyte marker C3, A2 type astrocyte marker S100A10, RAGE, tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor(BDNF), and insulin-like growth factor(IGF-1) in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group, oxygen glucose deprivation(OGD) group, OGD+GAS (0.34mmol/L) group and GAS group, and then the protein expressions of RAGE, TNF-α, BDNF and IGF-1 were detected by Western blotting and immunofluorescence. Results In vivo, Western blotting showed that compared with the sham group, the protein expression levels of C3, S100A10, RAGE, TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group (P <0.05), but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group (P <0.05). Compared with the HIBD group, the C3, RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group (P <0.05), and the protein expression levels of BDNF and IGF-1 further increased(P<0.05). The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment (P<0.05). The immunohistochemical staining results of C3, S100A10, and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results. Furthermore, the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes (P<0.05). After GAS intervention, while the expressions of both RAGE and TNF-α decreased significantly (P<0.05), the expressions of BDNF and IGF-1 increased significantly (P<0.05). Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors, gastrodin can promot the expressions of A2 astrocyte and nutritional factors, which play an important role in neuro-protective effect.

Key words

Receptor of advanced glycation endproduct

/ Astrocyte / Hypoxic-ischemic brain damage / Gastrodin / Western blotting / Neonatal rat

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

WANG Peng-xiang REN Xue-qi ZUO Han-jun WAN Cheng SHI Jin-sha SHI Hao-long ZHAO Min LI Juan-juan.

Effects of gastrodin on astrocyte phenotype and the receptor of advanced glycation endproducts expression after hypoxic-ischemic brain damage in neonatal rats

[J]. Acta Anatomica Sinica. 2024, 55(6): 677-684 https://doi.org/10.16098/j.issn.0529-1356.2024.06.004

References

［1］ Bone E, Andersson AL, Blomgren K, et al. Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats ［J］. Pediatr Res, 1999, 45(4 Pt1): 500-509.

［2］ Linnerbauer M, Rothhammer V. Protective functions of reactive astrocytes following central nervous system insult ［J］. Front Immunol, 2020, 11: 573256.

［3］ Liddelow SA, Barres BA. Reactive astrocytes: production, function, and therapeutic potential ［J］. Immunity, 2017, 46(6): 957-967.

［4］ Gonzalez-reyes RE, Rubiano MG. Astrocyte’s RAGE: more than just a question of mood ［J］. Cent Nerv Syst Agents Med Chem, 2018, 18(1): 39-48.

［5］ Han C, Lu Y, Wei Y, et al. D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation ［J］. Cell Death Dis, 2014, 5: e1117.

［6］ Ma JQ, Sun YZ, Ming QL, et al. Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway ［J］. Food Funct, 2020, 11(5): 4615-4624.

［7］ Guo J, Zhang XL, Bao ZR, et al. Gastrodin regulates the notch signaling pathway and Sirt3 in activated microglia in cerebral hypoxic-ischemia neonatal rats and in activated BV-2 microglia ［J］. Neuromolecular Med, 2021, 23(3): 348-362.

［8］ Molofsky AV, Deneen B. Astrocyte development: a guide for the perplexed ［J］. Glia, 2015, 63(8): 1320-1329.

［9］ Bhalala US, Koehler RC, Kannan S. Neuroinflammation and neuroimmune dysregulation after acute hypoxic-ischemic injury of developing brain ［J］. Front Pediatr, 2014, 2: 144.

［10］ Zhao N, Xu X, Jiang Y, et al. Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation ［J］. J Neuroinflammation, 2019, 16(1): 168.

［11］ Zong X, Li Y, Liu C, et al. Theta-burst transcranial magnetic stimulation promotes stroke recovery by vascular protection and neovascularization ［J］. Theranostics, 2020, 10(26): 12090-12110.

［12］ Donato R. RAGE: a single receptor for several ligands and different cellular responses: the case of certain S100 proteins ［J］. Curr Mol Med, 2007, 7(8): 711-724.

［13］ Yan SD, Chen X, Fu J, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease ［J］. Nature, 1996, 382(6593): 685-691.

［14］ Ramaswamy P, Goswami K, Dalavaikodihalli NN, et al. TNF-α mediated MEK-ERK signaling in invasion with putative network involving NF-κB and STAT-6: a new perspective in glioma ［J］. Cell Biol Int, 2019, 43(11): 1257-1266.

［15］ Madinier A, Bertrand N, Rodier M, et al. Ipsilateral versus contralateral spontaneous post-stroke neuroplastic changes: involvement of BDNF ［J］ ? Neuroscience, 2013, 231: 169-181.

［16］ Bejot Y, Prigent-tessier A, CACHIA C, et al. Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats ［J］. Neurochem Int, 2011, 58(1): 102-111.

［17］ Xu X, Zhang A, Zhu Y, et al. MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-kappaB and PI3K-Akt pathways ［J］. J Cell Physiol, 2018, 234(1): 904-914.

［18］ Zhao Y, Luo C, Chen J, et al. High glucose-induced complement component 3 up-regulation via RAGE-p38MAPK-NF-kappaB signalling in astrocytes: in vivo and in vitro studies ［J］. J Cell Mol Med, 2018, 22(12): 6087-6098.

［19］ Su Z, Yuan Y, Chen J, et al. Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-alpha ［J］. J Neurotrauma, 2011, 28(6): 1089-1100.

［20］ Depins B, Cifuentes-diaz C, Farah AT, et al. Conditional BDNF delivery from astrocytes rescues memory deficits, spine density, and synaptic properties in the 5xFAD mouse model of Alzheimer disease ［J］. J Neurosci, 2019, 39(13): 2441-2458.

［21］ Li X, Yu W, Guan Y, et al. Peripheral circulation and astrocytes contribute to the MSC-mediated increase in IGF-1 levels in the infarct cortex in a dMCAO rat model ［J］. Stem Cells Int, 2020, 2020: 8853444.

［22］ Liu J, Liu J, Liao HY, et al. Effects of resveratrol pretreatment on activation and inflammation ofastrocytes after oxygen-glucose deprivation/reoxygenation injury in vitro［J］. Acta Anatomica Sinica, 2020, 51 (3): 313-319. (in Chinese)

刘菁, 刘杰, 廖鸿雁,等. 白藜芦醇预处理对星形胶质细胞氧糖剥夺/再复氧损伤后活化及炎症反应的影响［J］. 解剖学报, 2020, 51 (3): 313-319.

［23］ Lin LC, Chen YF, Lee WC, et al. Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS/MS ［J］. J Pharm Biomed Anal, 2008, 48(3): 909-917.

［24］ Zhang HS, Ouyang B, JI XY, et al. Gastrodin alleviates cerebral ischaemia/reperfusion injury by inhibiting pyroptosis by regulating the lncRNA NEAT1/miR-22-3p Axis ［J］. Neurochem Res, 2021, 46(7): 1747-1758.

［25］ Sui Y, Bian L, Ai Q, et al. Gastrodin inhibits inflammasome through the STAT3 signal pathways in TNA2 astrocytes and reactive astrocytes in experimentally induced cerebral ischemia in rats ［J］. Neuromolecular Med, 2019, 21(3): 275-286.