Mechanisms and prospects of ischemic tolerance induced by cerebral preconditioning

Mohammad Iqbal Hossain Bhuiyan, Youn Jung Kim, Mohammad Iqbal Hossain Bhuiyan, Youn Jung Kim

Abstract

In the brain, brief episodes of ischemia induce tolerance against a subsequent severe episode of ischemia. This phenomenon of endogenous neuroprotection is known as preconditioning-induced ischemic tolerance. The purpose of this review is to summarize the current state of knowledge about mechanisms and potential applications of cerebral preconditioning and ischemic tolerance. Articles related to the terms ischemic preconditioning and ischemic tolerance were systematically searched via MEDLINE/PubMed, and articles published in English related to the nervous system were selected and analyzed. The past two decades have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. Although both rapid and delayed types of tolerance have been documented in experimental settings, the delayed type has been found to be more prominent in the case of neuronal ischemic tolerance. Many intracellular signaling pathways have been implicated regarding ischemic preconditioning. Most of these are associated with membrane receptors, kinase cascades, and transcription factors. Moreover, ischemic tolerance can be induced by exposing animals or cells to diverse types of endogenous and exogenous stimuli that are not necessarily hypoxic or ischemic in nature. These cross-tolerances raise the hope that, in the future, it will be possible to pharmacologically activate or mimic ischemic tolerance in the human brain. Another promising approach is remote preconditioning in which preconditioning of one organ or system leads to the protection of a different (remote) organ that is difficult to target, such as the brain. The preconditioning strategy and related interventions can confer neuroprotection in experimental ischemia, and, thus, have promise for practical applications in cases of vascular neurosurgery and endo-vascular therapy.

Keywords: Cerebral ischemia; Ischemic tolerance; Pharmacological preconditioning; Preconditioning; Remote preconditioning.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

References

    1. American Heart Association. Heart disease and stroke statistics: 2008 update. Dallas: Americna Heart Association; 2008.
    1. Grotta J. The current status of neuronal protective therapy: why have all neuronal protective drugs worked in animals but none so far in stroke patients. Cerebrovasc Dis. 1994;4:115–120.
    1. Smith WS. Pathophysiology of focal cerebral ischemia: a therapeutic perspective. J Vasc Interv Radiol. 2004;15(1 Pt 2):S3–S12.
    1. Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest. 2000;106:723–731.
    1. Kirino T. Ischemic tolerance. J Cereb Blood Flow Metab. 2002;22:1283–1296.
    1. Frerichs KU. Neuroprotective strategies in nature: novel clues for the treatment of stroke and trauma. Acta Neurochir Suppl. 1999;73:57–61.
    1. Drew KL, Rice ME, Kuhn TB, Smith MA. Neuroprotective adaptations in hibernation: therapeutic implications for ischemia-reperfusion, traumatic brain injury and neurodegenerative diseases. Free Radic Biol Med. 2001;31:563–573.
    1. Feder ME, Hofmann GE. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol. 1999;61:243–282.
    1. Janoff A. Alterations in lysosomes (intracellular enzymes) during shock: effects of preconditioning (tolerance) and protective drugs. Int Anesthesiol Clin. 1964;2:251–269.
    1. Dirnagl U, Simon RP, Hallenbeck JM. Ischemic tolerance and endogenous neuroprotection. Trends Neurosci. 2003;26:248–254.
    1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124–1136.
    1. Kume M, Yamamoto Y, Saad S, Gomi T, Kimoto S, Shimabukuro T, et al. Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury. J Lab Clin Med. 1996;128:251–258.
    1. Toosy N, McMorris EL, Grace PA, Mathie RT. Ischaemic preconditioning protects the rat kidney from reperfusion injury. BJU Int. 1999;84:489–494.
    1. Pasupathy S, Homer-Vanniasinkam S. Surgical implications of ischemic preconditioning. Arch Surg. 2005;140:405–409.
    1. Swain JL, Sabina RL, Hines JJ, Greenfield JC, Jr, Holmes EW. Repetitive episodes of brief ischaemia (12 min) do not produce a cumulative depletion of high energy phosphate compounds. Cardiovasc Res. 1984;18:264–269.
    1. Dahl NA, Balfour WM. Prolonged anoxic survival due to anoxia pre-exposure: brain atp, lactate, and pyruvate. Am J Physiol. 1964;207:452–456.
    1. Chopp M, Chen H, Ho KL, Dereski MO, Brown E, Hetzel FW, et al. Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat. Neurology. 1989;39:1396–1398.
    1. Schurr A, Reid KH, Tseng MT, West C, Rigor BM. Adaptation of adult brain tissue to anoxia and hypoxia in vitro. Brain Res. 1986;374:244–248.
    1. Kitagawa K, Matsumoto M, Kuwabara K, Tagaya M, Ohtsuki T, Hata R, et al. 'Ischemic tolerance' phenomenon detected in various brain regions. Brain Res. 1991;561:203–211.
    1. Stagliano NE, Pérez-Pinzón MA, Moskowitz MA, Huang PL. Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 1999;19:757–761.
    1. Xu GP, Dave KR, Vivero R, Schmidt-Kastner R, Sick TJ, Perez-Pinzon MA. Improvement in neuronal survival after ischemic preconditioning in hippocampal slice cultures. Brain Res. 2002;952:153–158.
    1. Bruer U, Weih MK, Isaev NK, Meisel A, Ruscher K, Bergk A, et al. Induction of tolerance in rat cortical neurons: hypoxic preconditioning. FEBS Lett. 1997;414:117–121.
    1. Moncayo J, de Freitas GR, Bogousslavsky J, Altieri M, van Melle G. Do transient ischemic attacks have a neuroprotective effect? Neurology. 2000;54:2089–2094.
    1. Ginis I, Jaiswal R, Klimanis D, Liu J, Greenspon J, Hallenbeck JM. TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. J Cereb Blood Flow Metab. 2002;22:142–152.
    1. Kapinya KJ, Löwl D, Fütterer C, Maurer M, Waschke KF, Isaev NK, et al. Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent. Stroke. 2002;33:1889–1898.
    1. Weih M, Bergk A, Isaev NK, Ruscher K, Megow D, Riepe M, et al. Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning. Neurosci Lett. 1999;272:207–210.
    1. Endres M, Gertz K, Lindauer U, Katchanov J, Schultze J, Schröck H, et al. Mechanisms of stroke protection by physical activity. Ann Neurol. 2003;54:582–590.
    1. Vlasov TD, Korzhevskii DE, Polyakova EA. Ischemic preconditioning of the rat brain as a method of endothelial protection from ischemic/repercussion injury. Neurosci Behav Physiol. 2005;35:567–572.
    1. Mehta SL, Manhas N, Raghubir R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev. 2007;54:34–66.
    1. Gidday JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006;7:437–448.
    1. Kapinya KJ. Ischemic tolerance in the brain. Acta Physiol Hung. 2005;92:67–92.
    1. Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol. 2009;8:398–412.
    1. Arundine M, Tymianski M. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium. 2003;34:325–337.
    1. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci U S A. 1995;92:4666–4670.
    1. Kawahara N, Ide T, Saito N, Kawai K, Kirino T. Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor. J Cereb Blood Flow Metab. 1998;18:472–475.
    1. Hiraide T, Katsura K, Muramatsu H, Asano G, Katayama Y. Adenosine receptor antagonists cancelled the ischemic tolerance phenomenon in gerbil. Brain Res. 2001;910:94–98.
    1. Grabb MC, Choi DW. Ischemic tolerance in murine cortical cell culture: critical role for NMDA receptors. J Neurosci. 1999;19:1657–1662.
    1. Marini AM, Popolo M, Pan H, Blondeau N, Lipsky RH. Brain adaptation to stressful stimuli: a new perspective on potential therapeutic approaches based on BDNF and NMDA receptors. CNS Neurol Disord Drug Targets. 2008;7:382–390.
    1. Tanaka H, Calderone A, Jover T, Grooms SY, Yokota H, Zukin RS, et al. Ischemic preconditioning acts upstream of GluR2 down-regulation to afford neuroprotection in the hippocampal CA1. Proc Natl Acad Sci U S A. 2002;99:2362–2367.
    1. Sommer C, Kiessling M. Ischemia and ischemic tolerance induction differentially regulate protein expression of GluR1, GluR2, and AMPA receptor binding protein in the gerbil hippocampus: GluR2 (GluR-B) reduction does not predict neuronal death. Stroke. 2002;33:1093–1100.
    1. Schwartz-Bloom RD, Sah R. Gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem. 2001;77:353–371.
    1. Sommer C, Fahrner A, Kiessling M. Postischemic neuroprotection in the ischemia-tolerant state gerbil hippocampus is associated with increased ligand binding to inhibitory GABA(A) receptors. Acta Neuropathol. 2003;105:197–202.
    1. Ma MC, Qian H, Ghassemi F, Zhao P, Xia Y. Oxygen-sensitive delta-opioid receptor-regulated survival and death signals: novel insights into neuronal preconditioning and protection. J Biol Chem. 2005;280:16208–16218.
    1. Noshita N, Lewén A, Sugawara T, Chan PH. Akt phosphorylation and neuronal survival after traumatic brain injury in mice. Neurobiol Dis. 2002;9:294–304.
    1. Ouyang YB, Tan Y, Comb M, Liu CL, Martone ME, Siesjo BK, et al. Survival- and death-promoting events after transient cerebral ischemia: phosphorylation of Akt, release of cytochrome C and activation of caspase-like proteases. J Cereb Blood Flow Metab. 1999;19:1126–1135.
    1. Nakajima T, Iwabuchi S, Miyazaki H, Okuma Y, Kuwabara M, Nomura Y, et al. Preconditioning prevents ischemia-induced neuronal death through persistent Akt activation in the penumbra region of the rat brain. J Vet Med Sci. 2004;66:521–527.
    1. Wick A, Wick W, Waltenberger J, Weller M, Dichgans J, Schulz JB. Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci. 2002;22:6401–6407.
    1. Alessandrini A, Namura S, Moskowitz MA, Bonventre JV. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc Natl Acad Sci U S A. 1999;96:12866–12869.
    1. Luo J, Kintner DB, Shull GE, Sun D. ERK1/2-p90RSK-mediated phosphorylation of Na+/H+ exchanger isoform 1. A role in ischemic neuronal death. J Biol Chem. 2007;282:28274–28284.
    1. Tauskela JS, chakravarthy BR, Murray CL, Wang Y, Comas T, Hogan M, et al. Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart. Brain Res. 1999;827:143–151.
    1. Gonzalez-Zulueta M, Feldman AB, Klesse LJ, Kalb RG, Dillman JF, Parada LF, et al. Requirement for nitric oxide activation of p21(ras)/extracellular regulated kinase in neuronal ischemic preconditioning. Proc Natl Acad Sci U S A. 2000;97:436–441.
    1. Zhang QG, Wang XT, Han D, Yin XH, Zhang GY, Xu TL. Akt inhibits MLK3/JNK3 signaling by inactivating Rac1: a protective mechanism against ischemic brain injury. J Neurochem. 2006;98:1886–1898.
    1. Tong H, Chen W, London RE, Murphy E, Steenbergen C. Preconditioning enhanced glucose uptake is mediated by p38 MAP kinase not by phosphatidylinositol 3-kinase. J Biol Chem. 2000;275:11981–11986.
    1. Hetman M, Kanning K, Cavanaugh JE, Xia Z. Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J Biol Chem. 1999;274:22569–22580.
    1. Shamloo M, Wieloch T. Rapid decline in protein kinase C gamma levels in the synaptosomal fraction of rat hippocampus after ischemic preconditioning. Neuroreport. 1999;10:931–935.
    1. Kurkinen K, Keinanen R, Li W, Koistinaho J. Preconditioning with spreading depression activates specifically protein kinase Cdelta. Neuroreport. 2001;12:269–273.
    1. Kawahara K, Yanoma J, Tanaka M, Nakajima T, Kosugi T. Nitric oxide produced during ischemia is toxic but crucial to preconditioning-induced ischemic tolerance of neurons in culture. Neurochem Res. 2004;29:797–804.
    1. Gidday JM, Shah AR, Maceren RG, Wang Q, Pelligrino DA, Holtzman DM, et al. Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning. J Cereb Blood Flow Metab. 1999;19:331–340.
    1. Centeno JM, Orti M, Salom JB, Sick TJ, Perez-Pinzon MA. Nitric oxide is involved in anoxic preconditioning neuroprotection in rat hippocampal slices. Brain Res. 1999;836:62–69.
    1. Nandagopal K, Dawson TM, Dawson VL. Critical role for nitric oxide signaling in cardiac and neuronal ischemic preconditioning and tolerance. J Pharmacol Exp Ther. 2001;297:474–478.
    1. Yun HY, Gonzalez-Zulueta M, Dawson VL, Dawson TM. Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras. Proc Natl Acad Sci U S A. 1998;95:5773–5778.
    1. Ginis I, Schweizer U, Brenner M, Liu J, Azzam N, Spatz M, et al. TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide. Am J Physiol. 1999;276(5 Pt 1):C1171–C1183.
    1. Castillo J, Moro MA, Blanco M, Leira R, Serena J, Lizasoain I, et al. The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke. Ann Neurol. 2003;54:811–819.
    1. Barone FC, White RF, Spera PA, Ellison J, Currie RW, Wang X, et al. Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke. 1998;29:1937–1950.
    1. Bhuiyan MI, Islam MN, Jung SY, Yoo HH, Lee YS, Jin C. Involvement of ceramide in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation in primary cultured cortical neurons of rats. Biol Pharm Bull. 2010;33:11–17.
    1. Liu J, Ginis I, Spatz M, Hallenbeck JM. Hypoxic preconditioning protects cultured neurons against hypoxic stress via TNF-alpha and ceramide. Am J Physiol Cell Physiol. 2000;278:C144–C153.
    1. Blondeau N, Widmann C, Lazdunski M, Heurteaux C. Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci. 2001;21:4668–4677.
    1. Kapinya K, Penzel R, Sommer C, Kiessling M. Temporary changes of the AP-1 transcription factor binding activity in the gerbil hippocampus after transient global ischemia, and ischemic tolerance induction. Brain Res. 2000;872:282–293.
    1. An G, Lin TN, Liu JS, Xue JJ, He YY, Hsu CY. Expression of c-fos and c-jun family genes after focal cerebral ischemia. Ann Neurol. 1993;33:457–464.
    1. Herdegen T, Waetzig V. AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration. Oncogene. 2001;20:2424–2437.
    1. Weih M, Kallenberg K, Bergk A, Dirnagl U, Harms L, Wernecke KD, et al. Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain? Stroke. 1999;30:1851–1854.
    1. Moncayo J, de Freitas GR, Bogousslavsky J, Altieri M, van Melle G. Do transient ischemic attacks have a neuroprotective effect? Neurology. 2000;54:2089–2094.
    1. Wegener S, Gottschalk B, Jovanovic V, Knab R, Fiebach JB, Schellinger PD, et al. Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke. 2004;35:616–621.
    1. Schaller B. Ischemic preconditioning as induction of ischemic tolerance after transient ischemic attacks in human brain: its clinical relevance. Neurosci Lett. 2005;377:206–211.
    1. Toyoda T, Kassell NF, Lee KS. Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A. J Neurosurg. 2000;92:435–441.
    1. Ohtsuki T, Matsumoto M, Taguchi A, Yang GM, Mabuchi T, Matsushita K, et al. Bifemelane hydrochloride enhances 'ischemic tolerance' phenomenon in gerbil hippocampal CA1 neurons. Life Sci. 1996;59:979–985.
    1. Morimoto RI, Santoro MG. Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection. Nat Biotechnol. 1998;16:833–838.
    1. Raval AP, Dave KR, Pérez-Pinzón MA. Resveratrol mimics ischemic preconditioning in the brain. J Cereb Blood Flow Metab. 2006;26:1141–1147.
    1. He W, Qian Zhong M, Zhu L, Christopher Q, Du F, Yung WH, et al. Ginkgolides mimic the effects of hypoxic preconditioning to protect C6 cells against ischemic injury by up-regulation of hypoxia-inducible factor-1 alpha and erythropoietin. Int J Biochem Cell Biol. 2008;40:651–662.
    1. Napolitano LM, Fabian TC, Kelly KM, Bailey JA, Block EF, Langholff W, et al. Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. J Trauma. 2008;65:285–297.
    1. Kitano H, Kirsch JR, Hurn PD, Murphy SJ. Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J Cereb Blood Flow Metab. 2007;27:1108–1128.
    1. Kapinya KJ, Prass K, Dirnagl U. Isoflurane induced prolonged protection against cerebral ischemia in mice: a redox sensitive mechanism? Neuroreport. 2002;13:1431–1435.
    1. Clarkson AN. Anesthetic-mediated protection/preconditioning during cerebral ischemia. Life Sci. 2007;80:1157–1175.
    1. Meco M, Cirri S, Gallazzi C, Magnani G, Cosseta D. Desflurane preconditioning in coronary artery bypass graft surgery: a double-blinded, randomised and placebo-controlled study. Eur J Cardiothorac Surg. 2007;32:319–325.
    1. Lucchinetti E, Aguirre J, Feng J, Zhu M, Suter M, Spahn DR, et al. Molecular evidence of late preconditioning after sevoflurane inhalation in healthy volunteers. Anesth Analg. 2007;105:629–640.
    1. Lucchinetti E, Ambrosio S, Aguirre J, Herrmann P, Härter L, Keel M, et al. Sevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans. Anesthesiology. 2007;106:262–268.
    1. Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation. 1997;96:1641–1646.
    1. Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008;79:377–386.
    1. Dave KR, Saul I, Prado R, Busto R, Perez-Pinzon MA. Remote organ ischemic preconditioning protect brain from ischemic damage following asphyxial cardiac arrest. Neurosci Lett. 2006;404:170–175.
    1. Ren C, Gao X, Steinberg GK, Zhao H. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Neuroscience. 2008;151:1099–1103.
    1. Ali ZA, Callaghan CJ, Lim E, Ali AA, Nouraei SA, Akthar AM, et al. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation. 2007;116(11 Suppl):I98–I105.
    1. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007;370:575–579.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir