Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury

Jun Hu , Zekai Hu , Jiayi Xia , Yeping Chen , Dennis Cordato , Qi Cheng , Jie Wang

Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (3) : 389 -404.

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Animal Models and Experimental Medicine ›› 2025, Vol. 8 ›› Issue (3) : 389 -404. DOI: 10.1002/ame2.12528
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Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury

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Abstract

Cerebral ischemia/reperfusion (I/R) injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways, including autophagy, apoptosis, necroptosis, and phagoptosis, among which autophagy is the most studied. We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury. To the best of our knowledge, this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke. The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.

Keywords

autophagy / cerebral ischemia / ischemia/reperfusion injury / stroke / treatment

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Jun Hu, Zekai Hu, Jiayi Xia, Yeping Chen, Dennis Cordato, Qi Cheng, Jie Wang. Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury. Animal Models and Experimental Medicine, 2025, 8(3): 389-404 DOI:10.1002/ame2.12528

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References

[1]

GBD 2021 Stroke Risk Factor Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the global burden of disease study 2021. Lancet Neurol. 2024; 23(10): 973-1003.

[2]

Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics—2023 update: a report from the American Heart Association. Circulation. 2023; 147(8): e93-e621.

[3]

Wei K, Wang P, Miao CY. A double-edged sword with therapeutic potential: an updated role of autophagy in ischemic cerebral injury. CNS Neurosci Ther. 2012; 18(11): 879-886.

[4]

Kalogeris T, Bao Y, Korthuis RJ. Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol. 2014; 2: 702-714.

[5]

Olowe R, Sandouka S, Saadi A, Shekh-Ahmad T. Approaches for reactive oxygen species and oxidative stress quantification in epilepsy. Antioxidants. 2020; 9(10): 990.

[6]

Ullah H, Di Minno A, Santarcangelo C, Khan H, Daglia M. Improvement of oxidative stress and mitochondrial dysfunction by beta-caryophyllene: a focus on the nervous system. Antioxidants. 2021; 10(4): 546.

[7]

Capucciati A, Zucca FA, Monzani E, Zecca L, Casella L, Hofer T. Interaction of neuromelanin with xenobiotics and consequences for neurodegeneration; promising experimental models. Antioxidants. 2021; 10(6): 824.

[8]

Woo J, Cho H, Seol Y, et al. Power failure of mitochondria and oxidative stress in neurodegeneration and its computational models. Antioxidants. 2021; 10(2): 229.

[9]

Kabir MT, Rahman MH, Shah M, et al. Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders. Biomed Pharmacother. 2022; 146: 112610.

[10]

Uddin MS, Stachowiak A, Mamun AA, et al. Autophagy and Alzheimer's disease: from molecular mechanisms to therapeutic implications. Front Aging Neurosci. 2018; 10: 4.

[11]

Shi R, Weng J, Zhao L, Li XM, Gao TM, Kong J. Excessive autophagy contributes to neuron death in cerebral ischemia. CNS Neurosci Ther. 2012; 18(3): 250-260.

[12]

Liu Y, Xue X, Zhang H, et al. Neuronal-targeted TFEB rescues dysfunction of the autophagy-lysosomal pathway and alleviates ischemic injury in permanent cerebral ischemia. Autophagy. 2019; 15(3): 493-509.

[13]

Lin SC, Hardie DG. AMPK: sensing glucose as well as cellular energy status. Cell Metab. 2018; 27(2): 299-313.

[14]

Hardie DG, Salt IP, Hawley SA, Davies SP. AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J. 1999; 338(Pt 3): 717-722.

[15]

Hinchy EC, Gruszczyk AV, Willows R, et al. Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem. 2018; 293(44): 17208-17217.

[16]

Lasek-Bal A, Jedrzejowska-Szypulka H, Rozycka J, et al. Low concentration of BDNF in the acute phase of ischemic stroke as a factor in poor prognosis in terms of functional status of patients. Med Sci Monit. 2015; 21: 3900-3905.

[17]

Yilmaz U, Tanbek K, Gul S, Koc A, Gul M, Sandal S. Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis. J Cell Mol Med. 2024; 28(8): e18246.

[18]

Deng L, Chen L, Zhao L, et al. Ubiquitination of Rheb governs growth factor-induced mTORC1 activation. Cell Res. 2019; 29(2): 136-150.

[19]

Shi H, Chapman NM, Wen J, et al. Amino acids license kinase mTORC1 activity and Treg cell function via small G proteins rag and Rheb. Immunity. 2019; 51(6): 1012-1027 e7.

[20]

Blommaart EF, Luiken JJ, Blommaart PJ, van Woerkom GM, Meijer AJ. Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem. 1995; 270(5): 2320-2326.

[21]

Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem. 1998; 273(23): 14484-14494.

[22]

Li A, Yuen VM, Goulay-Dufay S, Kwok PC. Pharmacokinetics and pharmacodynamics of dexmedetomidine. Drug Dev Ind Pharm. 2016; 42(12): 1917-1927.

[23]

Zhang F, Ding T, Yu L, Zhong Y, Dai H, Yan M. Dexmedetomidine protects against oxygen-glucose deprivation-induced injury through the I2 imidazoline receptor-PI3K/AKT pathway in rat C6 glioma cells. J Pharm Pharmacol. 2012; 64(1): 120-127.

[24]

Yan M, Dai H, Ding T, et al. Effects of dexmedetomidine on the release of glial cell line-derived neurotrophic factor from rat astrocyte cells. Neurochem Int. 2011; 58(5): 549-557.

[25]

Zhu C, Zhou Q, Luo C, Chen Y. Dexmedetomidine protects against oxygen-glucose deprivation-induced injury through inducing astrocytes autophagy via TSC2/mTOR pathway. Neuromolecular Med. 2020; 22(2): 210-217.

[26]

Ge S, Zhang L, Cui X, Li Y. Protective effects of brain-targeted dexmedetomidine nanomicelles on mitochondrial dysfunction in astrocytes of cerebral ischemia/reperfusion injury rats. Neuroscience. 2022; 498: 203-213.

[27]

Thomas J, Thomas CJ, Radcliffe J, Itsiopoulos C. Omega-3 fatty acids in early prevention of inflammatory neurodegenerative disease: a focus on Alzheimer's disease. Biomed Res Int. 2015; 2015: 172801.

[28]

Li M, Luo X, Long X, et al. Potential role of mitochondria in synoviocytes. Clin Rheumatol. 2021; 40(2): 447-457.

[29]

Tagde P, Tagde P, Islam F, et al. The multifaceted role of curcumin in advanced nanocurcumin form in the treatment and management of chronic disorders. Molecules. 2021; 26(23): 7109.

[30]

Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009; 284(18): 12297-12305.

[31]

Liu X, Tian F, Wang S, Wang F, Xiong L. Astrocyte autophagy flux protects neurons against oxygen-glucose deprivation and ischemic/reperfusion injury. Rejuvenation Res. 2018; 21(5): 405-415.

[32]

Wu M, Zhang H, Kai J, et al. Rapamycin prevents cerebral stroke by modulating apoptosis and autophagy in penumbra in rats. Ann Clin Transl Neurol. 2018; 5(2): 138-146.

[33]

Spilman P, Podlutskaya N, Hart MJ, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS ONE. 2010; 5(4): e9979.

[34]

Inoki K, Ouyang H, Zhu T, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006; 126(5): 955-968.

[35]

Gwinn DM, Shackelford DB, Egan DF, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30(2): 214-226.

[36]

Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011; 331(6016): 456-461.

[37]

Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011; 13(2): 132-141.

[38]

Shang L, Chen S, Du F, Li S, Zhao L, Wang X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci USA. 2011; 108(12): 4788-4793.

[39]

Bjorkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004; 24(5): 806-815.

[40]

Yu J, Li X, Matei N, et al. Ezetimibe, a NPC1L1 inhibitor, attenuates neuronal apoptosis through AMPK dependent autophagy activation after MCAO in rats. Exp Neurol. 2018; 307: 12-23.

[41]

Yang W, Shi H, Zhang J, Shen Z, Zhou G, Hu M. Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats. Lipids Health Dis. 2017; 16(1): 26.

[42]

Kamada H, Sato K, Iwai M, et al. Temporal and spatial changes of free cholesterol and neutral lipids in rat brain after transient middle cerebral artery occlusion. Neurosci Res. 2003; 45(1): 91-100.

[43]

Kudo M, Nagayama T. Light and electron microscopic study of lipid accumulation along margins of experimental cerebral infarcts in rats. Stroke. 1988; 19(12): 1544-1549.

[44]

Zhang JP, Sun GY. Free fatty acids, neutral glycerides, and phosphoglycerides in transient focal cerebral ischemia. J Neurochem. 1995; 64(4): 1688-1695.

[45]

Temel RE, Tang W, Ma Y, et al. Hepatic Niemann-pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007; 117(7): 1968-1978.

[46]

Yamamura T, Ohsaki Y, Suzuki M, et al. Inhibition of Niemann-pick-type C1-like1 by ezetimibe activates autophagy in human hepatocytes and reduces mutant alpha1-antitrypsin Z deposition. Hepatology. 2014; 59(4): 1591-1599.

[47]

Schmitz M, Signore SC, Zerr I, Althaus HH. Oligodendroglial process formation is differentially affected by modulating the intra- and extracellular cholesterol content. J Mol Neurosci. 2013; 49(3): 457-469.

[48]

Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P. Safety and efficacy of ezetimibe: a meta-analysis. Int J Cardiol. 2015; 201: 247-252.

[49]

Yang L, Zhao P, Zhao J, Wang J, Shi L, Wang X. Effects of ezetimibe and anticoagulant combined therapy on progressing stroke: a randomized, placebo-controlled study. J Neurol. 2016; 263(12): 2438-2445.

[50]

Le B, Yang SH. Identification of a novel potential probiotic lactobacillus plantarum FB003 isolated from salted-fermented shrimp and its effect on cholesterol absorption by regulation of NPC1L1 and PPARalpha. Probiotics Antimicrob Proteins. 2019; 11(3): 785-793.

[51]

Le B, Yang SH. Effect of potential probiotic Leuconostoc mesenteroides FB111 in prevention of cholesterol absorption by modulating NPC1L1/PPARalpha/SREBP-2 pathways in epithelial Caco-2 cells. Int Microbiol. 2019; 22(2): 279-287.

[52]

Mashurabad PC, Kondaiah P, Palika R, Ghosh S, Nair MK, Raghu P. Eicosapentaenoic acid inhibits intestinal beta-carotene absorption by downregulation of lipid transporter expression via PPAR-alpha dependent mechanism. Arch Biochem Biophys. 2016; 590: 118-124.

[53]

Valasek MA, Clarke SL, Repa JJ. Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse. J Lipid Res. 2007; 48(12): 2725-2735.

[54]

van der Veen JN, Kruit JK, Havinga R, et al. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005; 46(3): 526-534.

[55]

Sun J, Li X, Liu J, Pan X, Zhao Q. Stigmasterol exerts neuro-protective effect against ischemic/reperfusion injury through reduction of oxidative stress and inactivation of autophagy. Neuropsychiatr Dis Treat. 2019; 15: 2991-3001.

[56]

Zhao L, Zhang B, Cui Y, et al. 3-methyladenine alleviates excessive iodine-induced cognitive impairment via suppression of autophagy in rat hippocampus. Environ Toxicol. 2019; 34(8): 912-920.

[57]

Ding D, Xu S, Zhang H, et al. 3-methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy. Exp Ther Med. 2018; 15(4): 3516-3522.

[58]

Chen ZQ, Mou RT, Feng DX, Wang Z, Chen G. The role of nitric oxide in stroke. Med Gas Res. 2017; 7(3): 194-203.

[59]

Sun M, Zhao Y, Gu Y, Xu C. Inhibition of nNOS reduces ischemic cell death through down-regulating calpain and caspase-3 after experimental stroke. Neurochem Int. 2009; 54(5-6): 339-346.

[60]

Rahman MH, Akter R, Bhattacharya T, et al. Resveratrol and neuroprotection: impact and its therapeutic potential in Alzheimer's disease. Front Pharmacol. 2020; 11: 619024.

[61]

Ma X, Sun Z, Han X, et al. Neuroprotective effect of resveratrol via activation of Sirt1 signaling in a rat model of combined diabetes and Alzheimer's disease. Front Neurosci. 2019; 13: 1400.

[62]

Lee EO, Park HJ, Kang JL, Kim HS, Chong YH. Resveratrol reduces glutamate-mediated monocyte chemotactic protein-1 expression via inhibition of extracellular signal-regulated kinase 1/2 pathway in rat hippocampal slice cultures. J Neurochem. 2010; 112(6): 1477-1487.

[63]

Ao LY, Li WT, Zhou L, et al. Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy via AMPK-ULK1 signaling pathway in rats. Brain Res Bull. 2019; 153: 162-170.

[64]

Park JS, Shin JA, Jung JS, et al. Anti-inflammatory mechanism of compound K in activated microglia and its neuroprotective effect on experimental stroke in mice. J Pharmacol Exp Ther. 2012; 341(1): 59-67.

[65]

Bodalia A, Li H, Jackson MF. Loss of endoplasmic reticulum Ca2+ homeostasis: contribution to neuronal cell death during cerebral ischemia. Acta Pharmacol Sin. 2013; 34(1): 49-59.

[66]

Shi W, Xu D, Gu J, et al. Saikosaponin-d inhibits proliferation by up-regulating autophagy via the CaMKKbeta-AMPK-mTOR pathway in ADPKD cells. Mol Cell Biochem. 2018; 449(1-2): 219-226.

[67]

Lee CR, Chun JN, Kim SY, et al. Cyclosporin a suppresses prostate cancer cell growth through CaMKKbeta/AMPK-mediated inhibition of mTORC1 signaling. Biochem Pharmacol. 2012; 84(4): 425-431.

[68]

Zhang P, Liu X, Li H, et al. TRPC5-induced autophagy promotes drug resistance in breast carcinoma via CaMKKbeta/AMPKalpha/mTOR pathway. Sci Rep. 2017; 7(1): 3158.

[69]

Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334(6059): 1081-1086.

[70]

Xin Q, Ji B, Cheng B, et al. Endoplasmic reticulum stress in cerebral ischemia. Neurochem Int. 2014; 68: 18-27.

[71]

Santos-Galdiano M, Gonzalez-Rodriguez P, Font-Belmonte E, et al. Celecoxib-dependent neuroprotection in a rat model of transient middle cerebral artery occlusion (tMCAO) involves modifications in unfolded protein response (UPR) and proteasome. Mol Neurobiol. 2021; 58(4): 1404-1417.

[72]

Santos-Galdiano M, Perez-Rodriguez D, Anuncibay-Soto B, et al. Celecoxib treatment improves neurologic deficit and reduces selective neuronal loss and glial response in rats after transient middle cerebral artery occlusion. J Pharmacol Exp Ther. 2018; 367(3): 528-542.

[73]

Pei JJ, Sersen E, Iqbal K, Grundke-Iqbal I. Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals. Brain Res. 1994; 655(1-2): 70-76.

[74]

Zhu Y, Yu J, Gong J, et al. PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia. Aging (Albany NY). 2021; 13(3): 3405-3427.

[75]

Feng D, Wang B, Wang L, et al. Pre-ischemia melatonin treatment alleviated acute neuronal injury after ischemic stroke by inhibiting endoplasmic reticulum stress-dependent autophagy via PERK and IRE1 signalings. J Pineal Res. 2017; 62(3): e12395.

[76]

Xiang J, Zhu W, Yang F, et al. Melatonin-induced ApoE expression in mouse astrocytes protects endothelial cells from OGD-R induced injuries. Transl Psychiatry. 2020; 10(1): 181.

[77]

Kilic E, Kilic U, Reiter RJ, Bassetti CL, Hermann DM. Prophylactic use of melatonin protects against focal cerebral ischemia in mice: role of endothelin converting enzyme-1. J Pineal Res. 2004; 37(4): 247-251.

[78]

Grabacka MM, Gawin M, Pierzchalska M. Phytochemical modulators of mitochondria: the search for chemopreventive agents and supportive therapeutics. Pharmaceuticals. 2014; 7(9): 913-942.

[79]

Zhou T, Ye L, Bai Y, et al. Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog. PLoS ONE. 2014; 9(9): e107876.

[80]

Zhou DY, Zhang K, Conney AH, et al. Synthesis and evaluation of curcumin-related compounds containing benzyl piperidone for their effects on human cancer cells. Chem Pharm Bull. 2013; 61(11): 1149-1155.

[81]

Li Y, Wang Y, Kim E, et al. Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb. J Biol Chem. 2007; 282(49): 35803-35813.

[82]

Luo C, Ouyang MW, Fang YY, et al. Dexmedetomidine protects mouse brain from ischemia-reperfusion injury via inhibiting neuronal autophagy through up-regulating HIF-1alpha. Front Cell Neurosci. 2017; 11: 197.

[83]

Chen JL, Wang XX, Chen L, et al. A sphingosine kinase 2-mimicking TAT-peptide protects neurons against ischemia-reperfusion injury by activating BNIP3-mediated mitophagy. Neuropharmacology. 2020; 181: 108326.

[84]

Zhou JH, Zhang TT, Song DD, Xia YF, Qin ZH, Sheng R. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis. Sci Rep. 2016; 6: 27096.

[85]

Chen Z, Xu J, Wu Y, et al. Diosgenin inhibited the expression of TAZ in hepatocellular carcinoma. Biochem Biophys Res Commun. 2018; 503(3): 1181-1185.

[86]

Zhang X, Wang X, Khurm M, et al. Alterations of brain quantitative proteomics profiling revealed the molecular mechanisms of diosgenin against cerebral ischemia reperfusion effects. J Proteome Res. 2020; 19(3): 1154-1168.

[87]

Niso-Santano M, Shen S, Adjemian S, et al. Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy. Autophagy. 2013; 9(3): 415-417.

[88]

Wang L, Xiong X, Zhang X, et al. Sodium tanshinone IIA sulfonate protects against cerebral ischemia-reperfusion injury by inhibiting autophagy and inflammation. Neuroscience. 2020; 441: 46-57.

[89]

Zhang Y, Zhang Y, Jin XF, et al. The role of astragaloside IV against cerebral ischemia/reperfusion injury: suppression of apoptosis via promotion of P62-LC3-autophagy. Molecules. 2019; 24(9): 1838.

[90]

Yang J, Shao C, Li W, Wan H, He Y, Yang J. Protective effects of astragaloside IV against oxidative injury and apoptosis in cultured astrocytes by regulating Nrf2/JNK signaling. Exp Brain Res. 2021; 239(6): 1827-1840.

[91]

Abdullahi W, Tripathi D, Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection. Am J Physiol Cell Physiol. 2018; 315(3): C343-C356.

[92]

Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006; 7(1): 41-53.

[93]

Venna VR, Benashski SE, Chauhan A, McCullough LD. Inhibition of glycogen synthase kinase-3beta enhances cognitive recovery after stroke: the role of TAK1. Learn Mem. 2015; 22(7): 336-343.

[94]

Chuang DM, Wang Z, Chiu CT. GSK-3 as a target for lithium-induced neuroprotection against excitotoxicity in neuronal cultures and animal models of ischemic stroke. Front Mol Neurosci. 2011; 4: 15.

[95]

Teich AF, Sakurai M, Patel M, et al. PDE5 exists in human neurons and is a viable therapeutic target for neurologic disease. J Alzheimers Dis. 2016; 52(1): 295-302.

[96]

Gao J, Long L, Xu F, et al. Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase-3beta-mediated activation of autophagy. Br J Pharmacol. 2020; 177(6): 1434-1452.

[97]

Gao J, Ma C, Xia D, et al. Icariside II preconditioning evokes robust neuroprotection against ischaemic stroke, by targeting Nrf2 and the OXPHOS/NF-kappaB/ferroptosis pathway. Br J Pharmacol. 2022; 180: 308-329.

[98]

Kim YR, van Meer MP, Tejima E, et al. Functional MRI of delayed chronic lithium treatment in rat focal cerebral ischemia. Stroke. 2008; 39(2): 439-447.

[99]

Sharma VK, Singh TG, Garg N, et al. Dysbiosis and Alzheimer's disease: a role for chronic stress? Biomolecules. 2021; 11(5): 678.

[100]

Ait-Belgnaoui A, Colom A, Braniste V, et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil. 2014; 26(4): 510-520.

[101]

Abushouk AI, Negida A, Ahmed H, Abdel-Daim MM. Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity: future applications in Parkinson's disease. Biomed Pharmacother. 2017; 85: 635-645.

[102]

Schweizer S, Meisel A, Marschenz S. Epigenetic mechanisms in cerebral ischemia. J Cereb Blood Flow Metab. 2013; 33(9): 1335-1346.

[103]

International Stroke Genetics Consortium, Wellcome Trust Case Control Consortium, Bellenguez C, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012; 44(3): 328-333.

[104]

Shi W, Wei X, Wang Z, et al. HDAC9 exacerbates endothelial injury in cerebral ischaemia/reperfusion injury. J Cell Mol Med. 2016; 20(6): 1139-1149.

[105]

Arslan S, Berkan O, Lalem T, et al. Long non-coding RNAs in the atherosclerotic plaque. Atherosclerosis. 2017; 266: 176-181.

[106]

Vausort M, Wagner DR, Devaux Y. Long noncoding RNAs in patients with acute myocardial infarction. Circ Res. 2014; 115(7): 668-677.

[107]

Yu S, Yu M, He X, Wen L, Bu Z, Feng J. KCNQ1OT1 promotes autophagy by regulating miR-200a/FOXO3/ATG7 pathway in cerebral ischemic stroke. Aging Cell. 2019; 18(3): e12940.

[108]

Xu Q, Guohui M, Li D, et al. lncRNA C2dat2 facilitates autophagy and apoptosis via the miR-30d-5p/DDIT4/mTOR axis in cerebral ischemia-reperfusion injury. Aging (Albany NY). 2021; 13(8): 11315-11335.

[109]

Zhang J, Yuan L, Zhang X, et al. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia. Exp Neurol. 2016; 277: 162-170.

[110]

Yao X, Yao R, Huang F, Yi J. LncRNA SNHG12 as a potent autophagy inducer exerts neuroprotective effects against cerebral ischemia/reperfusion injury. Biochem Biophys Res Commun. 2019; 514(2): 490-496.

[111]

Gao W, Zhu M, Wang H, et al. Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population. Mutat Res. 2015; 772: 15-22.

[112]

Tragante V, Barnes MR, Ganesh SK, et al. Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci. Am J Hum Genet. 2014; 94(3): 349-360.

[113]

Wang J, Cao B, Han D, Sun M, Feng J. Long non-coding RNA H19 induces cerebral ischemia reperfusion injury via activation of autophagy. Aging Dis. 2017; 8(1): 71-84.

[114]

Wang J, Cao B, Zhao H, et al. Long noncoding RNA H19 prevents neurogenesis in ischemic stroke through p53/Notch1 pathway. Brain Res Bull. 2019; 150: 111-117.

[115]

Wang J, Cao B, Sun R, Chen Y, Feng J. Exosome-transported long non-coding ribonucleic acid H19 induces blood-brain barrier disruption in cerebral ischemic stroke via the H19/micro ribonucleic acid-18a/vascular endothelial growth factor axis. Neuroscience. 2022; 500: 41-51.

[116]

Wang J, Cao B, Gao Y, Chen YH, Feng J. Exosome-transported lncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke. Neural Regen Res. 2023; 18(6): 1316-1320.

[117]

Guo D, Ma J, Yan L, et al. Down-regulation of Lncrna MALAT1 attenuates neuronal cell death through suppressing Beclin1-dependent autophagy by regulating Mir-30a in cerebral ischemic stroke. Cell Physiol Biochem. 2017; 43(1): 182-194.

[118]

Wang H, Zheng X, Jin J, et al. LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4. J Biomed Sci. 2020; 27(1): 40.

[119]

Wang P, Liang J, Li Y, et al. Down-regulation of miRNA-30a alleviates cerebral ischemic injury through enhancing beclin 1-mediated autophagy. Neurochem Res. 2014; 39(7): 1279-1291.

[120]

Li Z, Li J, Tang N. Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-26b and upregulating ULK2 expression. Neuroscience. 2017; 354: 1-10.

[121]

Sun H, Zhong D, Wang C, Sun Y, Zhao J, Li G. MiR-298 exacerbates ischemia/reperfusion injury following ischemic stroke by targeting Act1. Cell Physiol Biochem. 2018; 48(2): 528-539.

[122]

Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019; 20(11): 675-691.

[123]

Han B, Zhang Y, Zhang Y, et al. Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: implications for cerebral ischemic stroke. Autophagy. 2018; 14(7): 1164-1184.

[124]

Deng M, Zhong X, Gao Z, et al. Dynamic changes in Beclin-1, LC3B and p62 at various time points in mice with temporary middle cerebral artery occlusion and reperfusion (tMCAO). Brain Res Bull. 2021; 173: 124-131.

[125]

Shiber A, Ravid T. Chaperoning proteins for destruction: diverse roles of Hsp70 chaperones and their co-chaperones in targeting misfolded proteins to the proteasome. Biomolecules. 2014; 4(3): 704-724.

[126]

Lippai M, Low P. The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. Biomed Res Int. 2014; 2014: 832704.

[127]

Shaid S, Brandts CH, Serve H, Dikic I. Ubiquitination and selective autophagy. Cell Death Differ. 2013; 20(1): 21-30.

[128]

Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J. 2009; 28(7): 889-901.

[129]

Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell. 2003; 115(6): 727-738.

[130]

Minoia M, Boncoraglio A, Vinet J, et al. BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch. Autophagy. 2014; 10(9): 1603-1621.

[131]

Liu X, Yamashita T, Shang J, et al. Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model. J Cereb Blood Flow Metab. 2020; 40(1): 214-224.

[132]

Mo Y, Sun YY, Liu KY. Autophagy and inflammation in ischemic stroke. Neural Regen Res. 2020; 15(8): 1388-1396.

[133]

Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010; 140(3): 313-326.

[134]

Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011; 147(4): 728-741.

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2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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