Advertisement

Autophagy and Ischemic Stroke

Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1207)

Abstract

Ischemic stroke refers to brain tissue ischemia, hypoxic necrosis, and brain softening caused by the interruption of the blood supply to the brain without adequate collateral circulation, thus resulting in neurological symptoms. Autophagy is activated in various cell types in the brain, such as neurons, glial cells, and microvascular cells, upon ischemic stroke. Autophagy efflux injury plays an important role in this pathologic process. This chapter outlines the induction of basal autophagy, autophagy in neurons, and the crosstalk between autophagy, necrosis, and apoptosis that contributes to ischemic stroke. We will highlight the interactions between autophagy, oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction, and the role of autophagy in ischemic stroke. We will also review the recent advances in the understanding of the involvement of autophagy in the pathological process of cerebral ischemic preconditioning, periconditioning, and postconditioning.

Keywords

Ischemic stroke Autophagy Apoptosis Necrosis Self-adaption 
This is a preview of subscription content, log in to check access.

References

  1. Adhami F, Schloemer A, Kuan CY (2007) The roles of autophagy in cerebral ischemia. Autophagy 3:42–44CrossRefGoogle Scholar
  2. Balduini W, Carloni S, Buonocore G (2009) Autophagy in hypoxia–ischemia induced brain injury: evidence and speculations. Autophagy 5:221–223CrossRefGoogle Scholar
  3. Boland B, Nixon RA (2006) Neuronal macroautophagy: from development to degeneration. Mol Aspects Med 27:503–519CrossRefGoogle Scholar
  4. Boland B, Kumar A, Lee S et al (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28:6926–6937CrossRefGoogle Scholar
  5. Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40:331–339CrossRefGoogle Scholar
  6. Bu Q, Liu X, Zhu Y et al (2014) W007B protects brain against ischemia–reperfusion injury in rats through inhibiting inflammation, apoptosis and autophagy. Brain Res 1558: 100–108Google Scholar
  7. Carloni S, Buonocore G, Balduini W (2008) Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol Dis 32:329–339CrossRefGoogle Scholar
  8. Carloni S, Girelli S, Scopa C et al (2010) Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 6: 366–377Google Scholar
  9. Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12: 1509–1518Google Scholar
  10. Ding WX, Ni HM, Gao W et al (2007) Linking autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol 171:513–524CrossRefGoogle Scholar
  11. Du L, Hickey RW, Bayir H et al (2009) Starving neurons show sex difference in autophagy. J Biol Chem 284:2383–2396CrossRefGoogle Scholar
  12. Fisher M (2011) New approaches to neuroprotective drug development. Stroke 42:24–27CrossRefGoogle Scholar
  13. Golstein P, Kroemer G (2007) Cell death by necrosis: towards a molecular definition. Trends Biochem Sci 32:37–43CrossRefGoogle Scholar
  14. Green AR, Shuaib A (2006) Therapeutic strategies for the treatment of stroke. Drug Discov Today 11:681–693CrossRefGoogle Scholar
  15. Guan R, Zou W, Dai X (2018) Mitophagy, a potential therapeutic target for stroke. J Biomed Sci 25:87CrossRefGoogle Scholar
  16. Høyer-Hansen M, Jäättelä M (2007) AMP-activated protein kinase: a universal regulator of autophagy? Autophagy 3: 381–383Google Scholar
  17. Jiang Z, Chen CH, Chen YY et al (2014) Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats. NeurNeurosci Lett 566:298–303CrossRefGoogle Scholar
  18. Kobayashi A, Czonkowska A (2005) Thrombolysis in acute ischemic stroke (Polish). Farmakoter Psychiatr Neurol 1:5–18Google Scholar
  19. Koike M, Shibata M, Tadakoshi M et al (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172:454–469CrossRefGoogle Scholar
  20. Krebiehl G, Ruckerbauer S, Burbulla LF et al (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s Disease-Associated Protein DJ-1. PLoS ONE 5:e9367CrossRefGoogle Scholar
  21. Kuma A, Hatano M, Matsui M et al (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032–1036CrossRefGoogle Scholar
  22. Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97CrossRefGoogle Scholar
  23. Li J, McCullough LD (2010) Effects of AMP-activated protein kinase in cerebral ischemia. J Cereb Blood Flow Metab 30:480–492CrossRefGoogle Scholar
  24. Liu C, Gao Y, Barrett J et al (2010) Autophagy and protein aggregation after brain ischemia. J Neurochem 115:68–78CrossRefGoogle Scholar
  25. Luo T, Park Y, Sun X et al (2013) Protein misfolding, aggregation, and autophagy after brain ischemia. Transl Stroke Res 4: 581–588Google Scholar
  26. Maiuri MC, Zalckvar E, Kimchi A et al (2007) Selfeating and self-killing: crosstalk between autophagy and apoptosis. Nature Rev Mol Cell Biol 8:741–752CrossRefGoogle Scholar
  27. Meloni BP, Meade AJ, Kitikomolsuk D et al (2011) Characterisation of neuronal cell death in acute and delayed in vitro ischemia (oxygen-glucose deprivation) models. J Neurosci Methods 195:67–74CrossRefGoogle Scholar
  28. Nabavi SF, Sureda A, Sanches-Silva A et al. (2019) Novel therapeutic strategies for stroke: the role of autophagy. Crit Rev Clin Lab Sci 1–18Google Scholar
  29. Park HK, Chu K, Jung KH et al (2009) Autophagy is involved in the ischemic preconditioning. Neurosci Lett 451:16–19CrossRefGoogle Scholar
  30. Rami A, Kögel D (2008) Apoptosis meets autophagy-like cell death in the ischemic penumbra: two sides of the same coin? Autophagy 4:422–426CrossRefGoogle Scholar
  31. Sarbassov DD, Guertin DA, Ali SM et al (2005) Phosphorylation and regulation of Akt/PKB by the rictormTOR complex. Science 307:1098–1101CrossRefGoogle Scholar
  32. Schieke SM, Phillips D, McCoy JP Jr et al (2006) The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 281:27643–27652CrossRefGoogle Scholar
  33. Semenza GL (2008) Mitochondrial autophagy: life and breath of the cell. Autophagy 4:534–536CrossRefGoogle Scholar
  34. Shang J, Deguchi K, Yamashita T et al (2010) Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats. J Neurosci Res 88:2197–2206CrossRefGoogle Scholar
  35. Sharp FR, Lu A, Tang Y et al (2000) Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab 20:1011–1032CrossRefGoogle Scholar
  36. Sheng R, Zhang LS, Han R et al (2010) Autophagy activation is associated with neuroprotection in a rat model of focal cerebral ischemic preconditioning. Autophagy 6:482–494CrossRefGoogle Scholar
  37. Tardy C, Codogno P, Autefage H et al (2006) Lysosomes and lysosomal proteins in cancer cell death (new players of an old struggle). Biochim Biophys Acta 1765:101–125PubMedGoogle Scholar
  38. Thorburn A (2008) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis 13:1–9CrossRefGoogle Scholar
  39. Uchiyama Y (2001) Autophagic cell death and its execution by lysosomal cathepsins. Arch Histol Cytol 64: 233–246Google Scholar
  40. Wang P, Shao BZ, Deng ZQ et al (2018) Autophagy in ischemic stroke. Prog Neurobiol.  https://doi.org/10.1016/j.pneurobio.2018.01.001CrossRefPubMedPubMedCentralGoogle Scholar
  41. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124:471–484CrossRefGoogle Scholar
  42. Yang Z, Klionsky DJ (2009) An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 335:1–32PubMedPubMedCentralGoogle Scholar
  43. Yu S, Yu M, He X et al (2019) KCNQ1OT1 promotes autophagy by regulating miR-200a/FOXO3/ATG7 pathway in cerebral ischemic stroke. Aging Cell e12940Google Scholar
  44. Zhang LL, Huang S, Ma XX et al (2016) Angiotensin (1-7) attenuated angiotensin II-induced hepatocyte EMT by inhibiting NOX-derived H2O2-activated NLRP3 inflammasome/IL-1β/Smad circuit. Free Radic Biol Med 97:531–543CrossRefGoogle Scholar
  45. Zhou X, Zhou J, Li X et al (2011) GSK-3 inhibitors suppressed neuroinflammation in rat cortex by activating autophagy in ischemic brain injury. Biochem Biophys Res Commun 411:271–275CrossRefGoogle Scholar

Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of NeurologyThe Second Affiliated Hospital of Soochow UniversitySuzhouChina

Personalised recommendations

Cite chapter

Buy options