Current Research in the Mechanism and Clinical Application about Remote Ischemic Preconditioning in Cerebral Infarction

doi:10.3969/j.issn.1673-5765.2024.01.014

Abstract

Abstract: Cerebral infarction is one of the diseases with high rates of disability and death worldwide, but there is still a lack of more effective treatments. Many studies showed that remote ischemic preconditioning (RIPC) can significantly improve ischemic tolerance of target organs, reduce infarct size and improve prognosis. However, its role and mechanism in the development of cerebral infarction are still little studied. This paper will summarize the role and mechanism of RIPC in cerebral infarction from the following aspects: neural, humoral, immune and related signaling pathways, and review the current research progress of RIPC in clinical cerebral ischemic diseases to provide a reference for subsequent research.

Key words: Cerebral infarction; Remote ischemic preconditioning; Cerebral protection; Signal transduction

摘要： 脑梗死是全球范围内致残率和致死率较高的疾病之一，大量研究表明，远端缺血预适应（remote ischemic preconditioning，RIPC）能够显著提高靶器官对缺血的耐受程度，减小梗死面积，改善患者预后，但目前对其在脑梗死发生发展中的作用机制研究较少。本文将从神经、体液和免疫3个方面，结合相关信号通路对RIPC在脑梗死中的作用及作用机制进行总结，并综述RIPC目前在临床缺血性脑疾病中的应用进展，以期为后续研究提供参考依据。

关键词: 脑梗死; 远端缺血预适应; 脑保护; 信号转导

CLC Number:

LIU Xudong, LIU Meng, SU Ying, ZHOU Yanxia, REN Lijie. Current Research in the Mechanism and Clinical Application about Remote Ischemic Preconditioning in Cerebral Infarction[J]. Chinese Journal of Stroke, 2024, 19(1): 105-111.

刘旭东, 刘萌, 苏颖, 周艳霞, 任力杰. 远端缺血预适应在脑梗死中的脑保护机制及临床应用研究进展[J]. 中国卒中杂志, 2024, 19(1): 105-111.

References

[1] KITAGAWA K，MATSUMOTO M，TAGAYA M，et al. ‘Ischemic tolerance’phenomenon found in the brain[J]. Brain Res，1990，528（1）：21-24.
[2] KITAGAWA K. Ischemic tolerance in the brain：endogenous adaptive machinery against ischemic stress[J]. J Neurosci Res，2012，90（5）：1043-1054.
[3] SHARMA D，MASLOV L N，SINGH N，et al. Remote ischemic preconditioning-induced neuroprotection in cerebral ischemia-reperfusion injury：preclinical evidence and mechanisms[J/OL]. Eur J Pharmacol，2020，883：173380[2022-10-11]. https://doi.org/10.1016/j.ejphar.2020.173380.
[4] BASALAY M V，WIART M，CHAUVEAU F，et al. Neuroprotection by remote ischemic conditioning in the setting of acute ischemic stroke：a preclinical two-centre study[J/OL]. Sci Rep，2020，10（1）：16874[2022-10-12]. https://doi.org/10.1038/s41598-020-74046-4.
[5] VIRANI S S，ALONSO A，APARICIO H J，et al. Heart disease and stroke statistics—2021 update：a report from the American Heart Association[J/OL]. Circulation，2021，143（8）：e254-e743[2022-10-08]. https://doi.org/10.1161/CIR.0000000000000950.
[6] FESKE S K. Ischemic stroke[J]. Am J Med，2021，134（12）：1457-1464.
[7] KITAGAWA K，SAITOH M，ISHIZUKA K，et al. Remote limb ischemic conditioning during cerebral ischemia reduces infarct size through enhanced collateral circulation in murine focal cerebral ischemia[J]. Stroke Cerebrovasc Dis，2018，27（4）：831-838.
[8] YUAN Q，JIA H X，LI S Q，et al. The role of adenosine in up-regulation of p38 MAPK and ERK during limb ischemic preconditioning-induced brain ischemic tolerance[J/OL]. Brain Res，2019，1707：172-183[2022-10-08]. https://doi.org/10.1016/j.brainres.2018.11.015.
[9] PAEZ D T，GARCES M，CALABRÓ V，et al. Adenosine A1 receptors and mitochondria：targets of remote ischemic preconditioning[J/OL]. Am J Physiol Heart Circ Physiol，2019，316（3）：H743-H750[2022-10-08].
https://doi.org/10.1152/ajpheart.00071.2018.
[10] LI P，SU L K，LI X F，et al. Remote limb ischemic postconditioning protects mouse brain against cerebral ischemia/reperfusion injury via upregulating expression of Nrf2，HO-1 and NQO-1 in mice[J]. Int J Neurosci，2016，126（6）：552-559.
[11] RASSAF T，TOTZECK M，HENDGEN-COTTA U B，et al. Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning[J]. Circ Res，2014，114（10）：1601-1610.
[12] CHAMORRO Á，DIRNAGL U，URRA X，et al. Neuroprotection in acute stroke：targeting excitotoxicity，oxidative and nitrosative stress，and inflammation[J]. Lancet Neurol，2016，15（8）：869-881.
[13] JAYARAJ RL，AZIMULLAH S，BEIRAM R，et al. Neuroinflammation：friend and foe for ischemic stroke[J/OL]. J Neuroinflammation，2019，16（1）：142[2022-10-08]. https://doi.org/10.1186/s12974-019-1516-2.
[14] MCDONALD M W，DYKES A，JEFFERS M S，et al. Remote ischemic conditioning and stroke recovery[J]. Neurorehabil Neural Repair，2021，35（6）：545-549.
[15] GUO Z N，GUO W T，LIU J，et al. Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning[J/OL]. Neurology，2019，93（1）：e8-e19[2022-10-08]. https://doi.org/10.1212/WNL.0000000000007732.
[16] LIANG W D，LIN C S，YUAN L Q，et al. Preactivation of Notch1 in remote ischemic preconditioning reduces cerebral ischemia-reperfusion injury through crosstalk with the NF-κB pathway[J/OL]. J Neuroinflammation，2019，16（1）：181[2022-10-08]. https://doi.org/10.1186/s12974-019-1570-9.
[17] PICKARD J M，DAVIDSON S M，HAUSENLOY D J，et al. Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning
[J/OL]. Basic Res Cardiol，2016，111（4）：50[2022-10-08].
https://doi.org/10.1007/s00395-016-0568-z.
[18] RANDHAWA P K，JAGGI A S. Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection[J/OL]. Life Sci，2016，155：140-146[2022-10-08]. https://doi.org/10.1016/j.lfs. 2016.05.009.
[19] WEI D T，REN C C，CHEN X Y，et al. The chronic protective effects of limb remote preconditioning and the underlying mechanisms involved in inflammatory factors in rat stroke[J/OL]. PLoS One，2012，7（2）：e30892[2022-10-08]. https://doi.org/10.1371/journal.pone.0030892.
[20] LANDMAN T R J，SCHOON Y，WARLÉ M C，et al. Remote ischemic conditioning as an additional treatment for acute ischemic stroke[J]. Stroke，2019，50（7）：1934-1939.
[21] LI C，SUN G C，CHEN B L，et al. Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke[J/OL]. Pharmacol Res，2021，174：105933[2022-10-08]. https://doi.org/10.1016/j.phrs. 2021.105933.
[22] LIU A D，GUO E S，YANG J K，et al. Ischemic preconditioning attenuates ischemia/reperfusion injury in rat steatotic liver：role of heme oxygenase-1-mediated autophagy[J]. Oncotarget，2016，7（48）：78372-78386.
[23] ZHANG X，WEI M P，FAN J H，et al. Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons[J]. Autophagy，2021，17（6）：1519-1542.
[24] CHENG X，ZHAO H P，YAN F，et al. Limb remote ischemic post-conditioning mitigates brain recovery in a mouse model of ischemic stroke by regulating reactive astrocytic plasticity[J/OL]. Brain Res，
2018，1686：94-100[2022-10-08]. https://doi.org/10.1016/j.brainres.2018.02.019.
[25] NAITO H，NOJIMA T，FUJISAKI N，et al. Therapeutic strategies for ischemia reperfusion injury in emergency medicine[J/OL]. Acute Med Surg，2020，7（1）：e501[2022-10-08]. https://doi.org/10.1002/ams2.501.
[26] YANG J H，VITERY M D C，CHEN J N，et al. Glutamate-releasing SWELL1 channel in astrocytes modulates synaptic transmission and promotes brain damage in Stroke[J/OL]. Neuron，2019，
102（4）：813-827，e6[2022-10-08]. https://doi.org/10.1016/j.neuron.2019.03.029.
[27] LIU C Y，YANG J，ZHANG C C，et al. Remote ischemic conditioning reduced cerebral ischemic injury by modulating inflammatory responses and ERK activity in type 2 diabetic mice[J/OL]. Neurochem Int，2020，135：104690[2022-10-08]. https://doi.org/10.1016/j.neuint.2020.104690.
[28] KHAN M B，HODA M N，VAIBHAV K，et al. Remote ischemic postconditioning：harnessing endogenous protection in a murine model of vascular cognitive impairment[J]. Transl Stroke Res，2015，6（1）：69-77.
[29] LIU Z J，CHEN C，LI X R，et al. Remote ischemic preconditioning-mediated neuroprotection against stroke is associated with significant alterations in peripheral immune responses[J]. CNS Neurosci Ther，2016，22（1）：43-52.
[30] VAHIDY F S，PARSHA K N，RAHBAR M H，et al. Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage[J]. J Cereb Blood Flow Metab，2016，36（6）：1012-1021.
[31] CHEN C，JIANG W，LIU Z J，et al. Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke[J/OL]. J Neuroinflammation，2018，15（1）：167[2022-10-08]. https://doi.org/10.1186/s12974-018-1190-9.
[32] SANTOS-GARCÍA D，BLANCO M，SERENA J，et al. Impaired brachial flow-mediated dilation is a predictor of a new-onset vascular event after stroke[J]. Cerebrovasc Dis，2011，32（2）：155-162.
[33] HYNGSTROM A S，NGUYEN J N，WRIGHT M T，et al. Two weeks of remote ischemic conditioning improves brachial artery flow mediated dilation in chronic stroke survivors[J]. J Appl Physiol（1985），2020，129（6）：1348-1354.
[34] POALELUNGI A，TULBĂ D，TURIAC E，et al. Remote ischemic conditioning may improve disability and cognition after acute ischemic stroke：a pilot randomized clinical trial[J/OL]. Front Neurol，2021，12：663400[2022-10-08]. https://doi.org/10.3389/fneur.2021.663400.
[35] AN J Q，CHENG Y W，GUO Y C，et al. Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke[J/OL]. Neurology，2020，95（24）：e3355-e3363[2022-10-08]. https://doi.org/10.1212/WNL.0000000000010884.
[36] WANG Y，MENG R，SONG H Q，et al. Remote ischemic conditioning may improve outcomes of patients with cerebral small-vessel disease[J]. Stroke，2017，48（11）：3064-3072.
[37] HODA M N，SIDDIQUI S，HERBERG S，et al. Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke[J]. Stroke，2012，43（10）：2794-2799.
[38] HE Y D，GUO Z N，QIN C，et al. Remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke[J]. Ann Clin Transl Neurol，2020，7（6）：972-979.
[39] DING J Y，SHANG S L，SUN Z S，et al. Remote ischemic conditioning for the treatment of ischemic moyamoya disease[J]. CNS Neurosci Ther，2020，26（5）：549-557.
[40] RABINSTEIN A A. Update on treatment of acute ischemic stroke[J]. Continuum（Minneap Minn），2020，26（2）：268-286.