Application of knowledge about ischemic tolerance to clinic requires the solid understanding of mechanism of creation of this phenomenon. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. The main emphasis is devoted to the possibility of preparing full tolerance in the donor's body and its transfer to the patient in the form of activated blood plasma. Such plasma could be administered as soon as the patient is transported to the hospital and would take effect immediately after administration to the patient's bloodstream. One chapter is also devoted to anticonditioning, i.e. the possibility of preventing the activation of tolerance. Anticonditioning could be used to treat oncologic patients. We expect that this method could increase effectiveness of cancer treatment. Cross-tolerance with a wide range of diverse stressors gives us the courage to assume that activated plasma can significantly help with a wide range of pathological events.

Institute of Neurobiology of Biomedical Research Center Slovak Academy of Sciences Košice Slovak Republic Faculty of Medicine Clinic of Trauma Surgery P J Šafárik University Košice Slovak Republic

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ANNUNZIATO L, PIGNATARO G, Di RENZO GF. Pharmacology of brain Na+/Ca2+ exchanger: from molecular biology to therapeutic perspectives. Pharmacol Rev. 2004;56:633–654. doi: 10.1124/pr.56.4.5. PubMed DOI

ATAR S, YE Y, LIN Y, FREEBERG SY, NISHI SP, ROSANIO S, HUANG MH, URETSKY BF, PEREZ-POLO JR, BIRNBAUM Y. Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2. Am J Physiol Heart Circ Physiol. 2006;290:H1960–H1968. doi: 10.1152/ajpheart.01137.2005. PubMed DOI

BARONE FC, WHITE RF, SPERA PA, ELLISON J, CURRIE RW, WANG X, FEUERSTEIN GZ. 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. doi: 10.1161/01.str.29.9.1937. discussion 1950–1931. PubMed DOI

BARTEKOVA M, RADOSINSKA J, PANCZA D, BARANCIK M, RAVINGEROVA T. Cardioprotective effects of quercetin against ischemia-reperfusion injury are age-dependent. Physiol Res. 2016;65(Suppl 1):S101–S107. doi: 10.33549/physiolres.933390. PubMed DOI

BIRNBAUM Y, YE Y, ROSANIO S, TAVACKOLI S, HU ZY, SCHWARZ ER, URETSKY BF. Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury. Cardiovasc Res. 2005;65:345–355. doi: 10.1016/j.cardiores.2004.10.018. PubMed DOI

BLONDEAU N, WIDMANN C, LAZDUNSKI M, HEURTEAUX C. Polyunsaturated fatty acids induce ischemic and epileptic tolerance. Neuroscience. 2002;109:231–241. doi: 10.1016/s0306-4522(01)00473-0. PubMed DOI

BODSCH W, TAKAHASHI K, BARBIER A, OPHOFF BG, HOSSMANN KA. Cerebral protein synthesis and ischemia. Prog Brain Res. 1985;63:197–210. doi: 10.1016/S0079-6123(08)61984-6. PubMed DOI

BORDET R, DEPLANQUE D, MABOUDOU P, PUISIEUX F, PU Q, ROBIN E, MARTIN A, BASTIDE M, LEYS D, LHERMITTE M, DUPUIS B. Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance. J Cereb Blood Flow Metab. 2000;20:1190–1196. doi: 10.1097/00004647-200008000-00004. PubMed DOI

BRAMBRINK AM, SCHNEIDER A, NOGA H, ASTHEIMER A, GOTZ B, KORNER I, HEIMANN A, WELSCHOF M, KEMPSKI O. Tolerance-inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning. J Cereb Blood Flow Metab. 2000;20:1425–1436. doi: 10.1097/00004647-200010000-00004. PubMed DOI

BURDA J, MARTIN ME, GARCIA A, ALCAZAR A, FANDO JL, SALINAS M. Phosphorylation of the alpha subunit of initiation factor 2 correlates with the inhibition of translation following transient cerebral ischaemia in the rat. Biochem J. 1994;302:335–338. doi: 10.1042/bj3020335. PubMed DOI PMC

BURDA J, MATIASOVA M, GOTTLIEB M, DANIELISOVA V, NEMETHOVA M, GARCIA L, SALINAS M, BURDA R. Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochem Res. 2005;30:1397–1405. doi: 10.1007/s11064-005-8510-z. PubMed DOI

BURDA J, DANIELISOVA V, NEMETHOVA M, GOTTLIEB M, KRAVCUKOVA P, DOMORAKOVA I, MECHIROVA E, BURDA R. Postconditioning and anticonditioning: possibilities to interfere to evoked apoptosis. Cell Mol Neurobiol. 2009;29:821–825. doi: 10.1007/s10571-009-9363-9. PubMed DOI PMC

BURDA J, HREHOROVSKA M, BONILLA LG, DANIELISOVA V, CIZKOVA D, BURDA R, NEMETHOVA M, FANDO JL, SALINAS M. Role of protein synthesis in the ischemic tolerance acquisition induced by transient forebrain ischemia in the rat. Neurochem Res. 2003;28:1213–1219. doi: 10.1023/a:1024232513106. PubMed DOI

BURDA J, DANIELISOVA V, NEMETHOVA M, GOTTLIEB M, MATIASOVA M, DOMORAKOVA I, MECHIROVA E, FERIKOVA M, SALINAS M, BURDA R. Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain. Cell Mol Neurobiol. 2006;26:1141–1151. doi: 10.1007/s10571-006-9036-x. PubMed DOI PMC

BURDA R, DANIELISOVÁ V, BURDA J. The end effector of ischemic tolerance present in blood plasma from double conditioned donors ameliorates trimethyltin provoked damage in brain. OBM Neurobiology. 2019;3:1–1. doi: 10.21926/obm.neurobiol.1903041. DOI

BURDA R, MOROCHOVIC R, NEMETHOVA M, BURDA J. Remote ischemic postconditioning as well as blood plasma from double-conditioned donor ameliorate reperfusion syndrome in skeletal muscle. J Plast Surg Hand Surg. 2020;54:59–65. doi: 10.1080/2000656X.2019.1688163. PubMed DOI

BURDA R, DANIELISOVA V, GOTTLIEB M, NEMETHOVA M, BONOVA P, MATIASOVA M, MOROCHOVIC R, BURDA J. Delayed remote ischemic postconditioning protects against transient cerebral ischemia/reperfusion as well as kainate-induced injury in rats. Acta Histochem. 2014;116:1062–1067. doi: 10.1016/j.acthis.2014.04.011. PubMed DOI

CHANG CZ, WU SC, LIN CL, HWANG SL, HOWNG SL, KWAN AL. Atorvastatin preconditioning attenuates the production of endothelin-1 and prevents experimental vasospasm in rats. Acta Neurochir (Wien) 2010;152:1399–1406. doi: 10.1007/s00701-010-0652-3. discussion 1405–1396. PubMed DOI

CHEN HI, HSIEH SY, YANG FL, HSU YH, LIN CC. Exercise training attenuates septic responses in conscious rats. Med Sci Sports Exerc. 2007;39:435–442. doi: 10.1249/mss.0b013e31802d11c8. PubMed DOI

CHEN Y, GINIS I, HALLENBECK JM. The protective effect of ceramide in immature rat brain hypoxia-ischemia involves up-regulation of bcl-2 and reduction of TUNEL-positive cells. J Cereb Blood Flow Metab. 2001;21:34–40. doi: 10.1097/00004647-200101000-00005. PubMed DOI

CHOPP M, CHEN H, HO KL, DERESKI MO, BROWN E, HETZEL FW, WELCH KM. Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat. Neurology. 1989;39:1396–1398. doi: 10.1212/wnl.39.10.1396. PubMed DOI

DANIELISOVA V, GOTTLIEB M, NEMETHOVA M, BURDA J. Effects of bradykinin postconditioning on endogenous antioxidant enzyme activity after transient forebrain ischemia in rat. Neurochem Res. 2008;33:1057–1064. doi: 10.1007/s11064-007-9550-3. PubMed DOI

DANIELISOVA V, GOTTLIEB M, NEMETHOVA M, KRAVCUKOVA P, DOMORAKOVA I, MECHIROVA E, BURDA J. Bradykinin postconditioning protects pyramidal CA1 neurons against delayed neuronal death in rat hippocampus. Cell Mol Neurobiol. 2009;29:871–878. doi: 10.1007/s10571-009-9369-3. PubMed DOI PMC

DICKSON EW, REINHARDT CP, RENZI FP, BECKER RC, PORCARO WA, HEARD SO. Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis. 1999;8:123–129. doi: 10.1023/a:1008911101951. PubMed DOI

DICKSON EW, BLEHAR DJ, CARRAWAY RE, HEARD SO, STEINBERG G, PRZYKLENK K. Naloxone blocks transferred preconditioning in isolated rabbit hearts. J Mol Cell Cardiol. 2001;33:1751–1756. doi: 10.1006/jmcc.2001.1436. PubMed DOI

DIENEL GA, PULSINELLI WA, DUFFY TE. Regional protein synthesis in rat brain following acute hemispheric ischemia. J Neurochem. 1980;35:1216–1226. doi: 10.1111/j.1471-4159.1980.tb07878.x. PubMed DOI

DILLON JP, LAING AJ, CHANDLER JR, WANG JH, McGUINNESS A, REDMOND HP. Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury. Acta Orthop. 2006;77:27–32. doi: 10.1080/17453670610045669. PubMed DOI

DIRNAGL U, MEISEL A. Endogenous neuroprotection: Mitochondria as gateways to cerebral preconditioning? Neuropharmacology. 2008;55:334–344. doi: 10.1016/j.neuropharm.2008.02.017. PubMed DOI

DIRNAGL U, SIMON RP, HALLENBECK JM. Ischemic tolerance and endogenous neuroprotection. Trends Neurosci. 2003;26:248–254. doi: 10.1016/S0166-2236(03)00071-7. PubMed DOI

DOMORAKOVA I, MECHIROVA E, DANKOVA M, DANIELISOVA V, BURDA J. Effect of antioxidant treatment in global ischemia and ischemic postconditioning in the rat hippocampus. Cell Mol Neurobiol. 2009;29:837–844. doi: 10.1007/s10571-009-9365-7. PubMed DOI PMC

DURUKAN A, TATLISUMAK T. Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection. Exp Transl Stroke Med. 2010;2:2. doi: 10.1186/2040-7378-2-2. PubMed DOI PMC

FERDINANDY P, HAUSENLOY DJ, HEUSCH G, BAXTER GF, SCHULZ R. Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev. 2014;66:1142–1174. doi: 10.1124/pr.113.008300. PubMed DOI

FUJIKI M, KOBAYASHI H, ABE T, KAMIDA T. Repetitive transcranial magnetic stimulation for protection against delayed neuronal death induced by transient ischemia. J Neurosurg. 2003;99:1063–1069. doi: 10.3171/jns.2003.99.6.1063. PubMed DOI

GAGE AT, STANTON PK. Hypoxia triggers neuroprotective alterations in hippocampal gene expression via a heme-containing sensor. Brain Res. 1996;719:172–178. doi: 10.1016/0006-8993(96)00092-3. PubMed DOI

GIDDAY JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006;7:437–448. doi: 10.1038/nrn1927. PubMed DOI

GOTO M, LIU Y, YANG XM, ARDELL JL, COHEN MV, DOWNEY JM. Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res. 1995;77:611–621. doi: 10.1161/01.res.77.3.611. PubMed DOI

HAO Y, XIN M, FENG L, WANG X, WANG X, MA D, FENG J. Review cerebral ischemic tolerance and preconditioning: Methods, mechanisms, clinical applications, and challenges. Front Neurol. 2020;11:812. doi: 10.3389/fneur.2020.00812. PubMed DOI PMC

HEUSCH G, GERSH BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J. 2017;38:774–784. doi: 10.1093/eurheartj/ehw224. PubMed DOI

HU BR, WIELOCH T. Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat. J Neurosci. 1993;13:1830–1838. doi: 10.1523/JNEUROSCI.13-05-01830.1993. PubMed DOI PMC

JOSEPH B, PANDIT V, ZANGBAR B, KULVATUNYOU N, KHALIL M, TANG A, O’KEEFFE T, GRIES L, VERCRUYSSE G, FRIESE RS, RHEE P. Secondary brain injury in trauma patients: the effects of remote ischemic conditioning. J Trauma Acute Care Surg. 2015;78:698–703. doi: 10.1097/TA.0000000000000584. discussion 703–695. PubMed DOI

KAPLAN P, TATARKOVA Z, LICHARDUSOVA L, KMETOVA SIVONOVA M, TOMASCOVA A, RACAY P, LEHOTSKY J. Age-associated changes in antioxidants and redox proteins of rat heart. Physiol Res. 2019;68:883–892. doi: 10.33549/physiolres.934170. PubMed DOI

KAWAHARA N, RUETZLER CA, MIES G, KLATZO I. Cortical spreading depression increases protein synthesis and upregulates basic fibroblast growth factor. Exp Neurol. 1999;158:27–36. doi: 10.1006/exnr.1999.7091. PubMed DOI

KIRINO T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982;239:57–69. doi: 10.1016/0006-8993(82)90833-2. PubMed DOI

KIRINO T, TSUJITA Y, TAMURA A. Induced tolerance to ischemia in gerbil hippocampal neurons. J Cereb Blood Flow Metab. 1991;11:299–307. doi: 10.1038/jcbfm.1991.62. PubMed DOI

KITAGAWA K, MATSUMOTO M, KUWABARA K, TAGAYA M, OHTSUKI T, HATA R, UEDA H, HANDA N, KIMURA K, KAMADA T. ‘Ischemic tolerance’ phenomenon detected in various brain regions. Brain Res. 1991;561:203–211. doi: 10.1016/0006-8993(91)91596-s. PubMed DOI

KOKOSOVA N, DANIELISOVA V, SMAJDA B, BURDA J. Ionizing radiation as preconditioning against transient cerebral ischemia in rats. Gen Physiol Biophys. 2014;33:403–410. doi: 10.4149/gpb_2014021. PubMed DOI

KRISTIAN T, SIESJO BK. Calcium-related damage in ischemia. Life Sci. 1996;59:357–367. doi: 10.1016/0024-3205(96)00314-1. PubMed DOI

KROKOWICZ L, KLIMCZAK A, CWYKIEL J, MIELNICZUK M, GRYKIEN C, SIEMIONOW M. Pulsed acoustic cellular expression as a protective therapy against I/R injury in a cremaster muscle flap model. Microvasc Res. 2012;83:213–222. doi: 10.1016/j.mvr.2011.11.005. PubMed DOI

KUROIWA T, YAMADA I, ENDO S, HAKAMATA Y, ITO U. 3-Nitropropionic acid preconditioning ameliorates delayed neurological deterioration and infarction after transient focal cerebral ischemia in gerbils. Neurosci Lett. 2000;283:145–148. doi: 10.1016/s0304-3940(00)00937-x. PubMed DOI

LEHOTSKY J, BURDA J, DANIELISOVA V, GOTTLIEB M, KAPLAN P, SANIOVA B. Ischemic tolerance: the mechanisms of neuroprotective strategy. Anat Rec (Hoboken) 2009;292:2002–2012. doi: 10.1002/ar.20970. PubMed DOI

LOUKOGEORGAKIS SP, WILLIAMS R, PANAGIOTIDOU AT, KOLVEKAR SK, DONALD A, COLE TJ, YELLON DM, DEANFIELD JE, MacALLISTER RJ. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007;116:1386–1395. doi: 10.1161/CIRCULATIONAHA.106.653782. PubMed DOI

MATSUSHIMA K, SCHMIDT-KASTNER R, HOGAN MJ, HAKIM AM. Cortical spreading depression activates trophic factor expression in neurons and astrocytes and protects against subsequent focal brain ischemia. Brain Res. 1998;807:47–60. doi: 10.1016/s0006-8993(98)00716-1. PubMed DOI

MENG X, CLEVELAND JC, JR, ROWLAND RT, MITCHELL MB, BROWN JM, BANERJEE A, HARKEN AH. Norepinephrine-induced sustained myocardial adaptation to ischemia is dependent on alpha 1-adrenoceptors and protein synthesis. J Mol Cell Cardiol. 1996;28:2017–2025. doi: 10.1006/jmcc.1996.0194. PubMed DOI

MURRY CE, JENNINGS RB, REIMER KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124–1136. doi: 10.1161/01.cir.74.5.1124. PubMed DOI

NAGY D, KOCSIS K, FUZIK J, MAROSI M, KIS Z, TEICHBERG VI, TOLDI J, FARKAS T. Kainate postconditioning restores LTP in ischemic hippocampal CA1: onset-dependent second pathophysiological stress. Neuropharmacology. 2011;61:1026–1032. doi: 10.1016/j.neuropharm.2011.07.005. PubMed DOI

NIQUET J, SEO DW, WASTERLAIN CG. Mitochondrial pathways of neuronal necrosis. Biochem Soc Trans. 2006;34:1347–1351. doi: 10.1042/BST0341347. PubMed DOI

NISHIO S, CHEN ZF, YUNOKI M, TOYODA T, ANZIVINO M, LEE KS. Hypothermia-induced ischemic tolerance. Ann N Y Acad Sci. 1999;890:26–41. doi: 10.1111/j.1749-6632.1999.tb07978.x. PubMed DOI

OHTSUKI T, MATSUMOTO M, KUWABARA K, KITAGAWA K, SUZUKI K, TANIGUCHI N, KAMADA T. Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons. Brain Res. 1992;599:246–252. doi: 10.1016/0006-8993(92)90398-s. PubMed DOI

PAGLIARO P, FEMMINO S, POPARA J, PENNA C. Mitochondria in cardiac postconditioning. Front Physiol. 2018;9:287. doi: 10.3389/fphys.2018.00287. PubMed DOI PMC

PASCHEN W. Glutamate excitotoxicity in transient global cerebral ischemia. Acta Neurobiol Exp (Wars) 1996;56:313–322. PubMed

PEREZ-PINZON MA, XU GP, DIETRICH WD, ROSENTHAL M, SICK TJ. Rapid preconditioning protects rats against ischemic neuronal damage after 3 but not 7 days of reperfusion following global cerebral ischemia. J Cereb Blood Flow Metab. 1997;17:175–182. doi: 10.1097/00004647-199702000-00007. PubMed DOI

PIGNATARO G, BRANCACCIO P, LAUDATI G, VALSECCHI V, ANZILOTTI S, CASAMASSA A, CUOMO O, VINCIGUERRA A. Sodium/calcium exchanger as main effector of endogenous neuroprotection elicited by ischemic tolerance. Cell Calcium. 2020;87:102183. doi: 10.1016/j.ceca.2020.102183. PubMed DOI

PRZYKLENK K. Efficacy of cardioprotective ‘conditioning’ strategies in aging and diabetic cohorts: the co-morbidity conundrum. Drugs Aging. 2011;28:331–343. doi: 10.2165/11587190-000000000-00000. PubMed DOI

PRZYKLENK K, BAUER B, OVIZE M, KLONER RA, WHITTAKER P. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993;87:893–899. doi: 10.1161/01.cir.87.3.893. PubMed DOI

PUISIEUX F, DEPLANQUE D, PU Q, SOUIL E, BASTIDE M, BORDET R. Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance. Eur J Pharmacol. 2000;389:71–78. doi: 10.1016/s0014-2999(99)00893-6. PubMed DOI

PUISIEUX F, DEPLANQUE D, BULCKAEN H, MABOUDOU P, GELE P, LHERMITTE M, LEBUFFE G, BORDET R. Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase. Brain Res. 2004;1027:30–37. doi: 10.1016/j.brainres.2004.08.067. PubMed DOI

PULSINELLI WA, BRIERLEY JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke. 1979;10:267–272. doi: 10.1161/01.str.10.3.267. PubMed DOI

RAVINGEROVA T, PYNE NJ, PARRATT JR. Ischaemic preconditioning in the rat heart: the role of G-proteins and adrenergic stimulation. Mol Cell Biochem. 1995;147:123–128. doi: 10.1007/BF00944792. PubMed DOI

RAVINGEROVA T, PANCZA D, ZIEGELHOFFER A, STYK J. Preconditioning modulates susceptibility to ischemia-induced arrhythmias in the rat heart: the role of alpha-adrenergic stimulation and K(ATP) channels. Physiol Res. 2002;51:109–119. PubMed

RIEPE MW, LUDOLPH AC. Chemical preconditioning: a cytoprotective strategy. Mol Cell Biochem. 1997;174:249–254. PubMed

RIKSEN NP, SMITS P, RONGEN GA. Ischaemic preconditioning: from molecular characterisation to clinical application--part I. Neth J Med. 2004;62:353–363. PubMed

SAAD MA, ABDELSALAM RM, KENAWY SA, ATTIA AS. Ischemic preconditioning and postconditioning alleviates hippocampal tissue damage through abrogation of apoptosis modulated by oxidative stress and inflammation during transient global cerebral ischemia-reperfusion in rats. Chem Biol Interact. 2015;232:21–29. doi: 10.1016/j.cbi.2015.03.007. PubMed DOI

SHIMIZU M, TROPAK M, DIAZ RJ, SUTO F, SURENDRA H, KUZMIN E, LI J, GROSS G, WILSON GJ, CALLAHAN J, REDINGTON AN. Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. Clin Sci (Lond) 2009;117:191–200. doi: 10.1042/CS20080523. PubMed DOI

SIRACUSANO L, GIRASOLE V, ALVARO S, CHIAVARINO ND. Myocardial preconditioning and cardioprotection by volatile anaesthetics. J Cardiovasc Med (Hagerstown) 2006;7:86–95. doi: 10.2459/01.JCM.0000199792.32479.ce. PubMed DOI

SUGINO T, NOZAKI K, TAKAGI Y, HASHIMOTO N. 3-Nitropropionic acid induces ischemic tolerance in gerbil hippocampus in vivo. Neurosci Lett. 1999;259:9–12. doi: 10.1016/s0304-3940(98)00875-1. PubMed DOI

TASAKI K, RUETZLER CA, OHTSUKI T, MARTIN D, NAWASHIRO H, HALLENBECK JM. Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res. 1997;748:267–270. doi: 10.1016/s0006-8993(96)01383-2. PubMed DOI

TOBALEM M, WETTSTEIN R, PITTET-CUENOD B, VIGATO E, MACHENS HG, LOHMEYER JA, REZAEIAN F, HARDER Y. Local shockwave-induced capillary recruitment improves survival of musculocutaneous flaps. J Surg Res. 2013;184:1196–1204. doi: 10.1016/j.jss.2013.03.040. PubMed DOI

TOYODA T, KASSELL NF, LEE KS. Induction of ischemic tolerance and antioxidant activity by brief focal ischemia. Neuroreport. 1997;8:847–851. doi: 10.1097/00001756-199703030-00008. PubMed DOI

TSUBOTA H, MARUI A, ESAKI J, BIR SC, IKEDA T, SAKATA R. Remote postconditioning may attenuate ischaemia-reperfusion injury in the murine hindlimb through adenosine receptor activation. Eur J Vasc Endovasc Surg. 2010;40:804–809. doi: 10.1016/j.ejvs.2010.08.014. PubMed DOI

TYAGI S, SINGH N, VIRDI JK, JAGGI AS. Diabetes abolish cardioprotective effects of remote ischemic conditioning: evidences and possible mechanisms. J Physiol Biochem. 2019;75:19–28. doi: 10.1007/s13105-019-00664-w. PubMed DOI

WADA K, ITO M, MIYAZAWA T, KATOH H, NAWASHIRO H, SHIMA K, CHIGASAKI H. Repeated hyperbaric oxygen induces ischemic tolerance in gerbil hippocampus. Brain Res. 1996;740:15–20. doi: 10.1016/s0006-8993(96)00831-1. PubMed DOI

WADA K, MIYAZAWA T, NOMURA N, YANO A, TSUZUKI N, NAWASHIRO H, SHIMA K. Mn-SOD and Bcl-2 expression after repeated hyperbaric oxygenation. Acta Neurochir Suppl. 2000;76:285–290. doi: 10.1007/978-3-7091-6346-7_59. PubMed DOI

WANG WZ, STEPHESON LL, FANG XH, KHIABANI KT, ZAMBONI WA. Ischemic preconditioning-induced microvascular protection at a distance. J Reconstr Microsurg. 2004;20:175–181. doi: 10.1055/s-2004-820775. PubMed DOI

WIDMANN R, KUROIWA T, BONNEKOH P, HOSSMANN KA. [14C]leucine incorporation into brain proteins in gerbils after transient ischemia: relationship to selective vulnerability of hippocampus. J Neurochem. 1991;56:789–796. doi: 10.1111/j.1471-4159.1991.tb01993.x. PubMed DOI

YOU J, FENG L, XIN M, MA D, FENG J. Cerebral ischemic postconditioning plays a neuroprotective role through regulation of central and peripheral glutamate. Biomed Res Int. 2018;2018:6316059. doi: 10.1155/2018/6316059. PubMed DOI PMC

ZHANG WQ, MIAO YF, ZHOU SQ, JIANG JY, LUO QZ, QIU YM. Neuroprotective effects of ischemic postconditioning on global brain ischemia in rats through upregulation of hippocampal glutamine synthetase. J Clin Neurosci. 2011;18:685–689. doi: 10.1016/j.jocn.2010.08.027. PubMed DOI

ZHAO H, REN C, CHEN X, SHEN J. From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia. Curr Drug Targets. 2012;13:173–187. doi: 10.2174/138945012799201621. PubMed DOI PMC

ZHAO ZQ, CORVERA JS, HALKOS ME, KERENDI F, WANG NP, GUYTON RA, VINTEN-JOHANSEN J. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285:H579–H588. doi: 10.1152/ajpheart.01064.2002. PubMed DOI

ZHAO YX, CUI M, CHEN SF, DONG Q, LIU XY. Amelioration of ischemic mitochondrial injury and Bax-dependent outer membrane permeabilization by Mdivi-1. CNS Neurosci Ther. 2014;20:528–538. doi: 10.1111/cns.12266. PubMed DOI PMC