scholarly journals Remote postconditioning ameliorates stroke damage by preventing let-7a and miR-143 up-regulation

Theranostics ◽  
2020 ◽  
Vol 10 (26) ◽  
pp. 12174-12188
Author(s):  
Antonio Vinciguerra ◽  
Pasquale Cepparulo ◽  
Serenella Anzilotti ◽  
Ornella Cuomo ◽  
Valeria Valsecchi ◽  
...  
Keyword(s):  
Remote Postconditioning

scholarly journals The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Valeria Valsecchi ◽  
Giusy Laudati ◽  
Ornella Cuomo ◽  
Rossana Sirabella ◽  
Lucio Annunziato ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Ischemia ◽  
Femoral Artery ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Sodium Calcium Exchanger ◽  
Protein Levels ◽  
Relevant Role ◽  
Remote Postconditioning

AbstractRemote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at −23/−17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology.

Abstract P129: Role of the Autonomic Nervous System in Remote Postconditioning in Humans

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rupert P Williams ◽  
Michael I Okorie ◽  
Harminder Gill ◽  
John E Deanfield ◽  
Raymond J MacAllister ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Whole Body ◽  
Limb Ischaemia ◽  
Protective Effects ◽  
Blood Pressure Cuff ◽  
Autonomic Nervous ◽  
Pressure Cuff ◽  
Remote Postconditioning

Brief periods of ischaemia activate systemic mechanisms that induce whole-body tolerance to subsequent prolonged and injurious ischaemia. This phenomenon, remote ischaemic preconditioning (RIPC), is sufficiently acute to reduce ischaemia-reperfusion (IR) injury even when applied simultaneously with injurious ischaemia. This aspect of RIPC is termed remote postconditioning (RPostC). We have previously demonstrated a role for the autonomic nervous system in RIPC. Using an in vivo model of endothelial IR injury, we determined if RPostC is dependent on adrenergic autonomic mechanisms. Vascular ultrasound was used to assess endothelial function in healthy volunteers by measuring dilatation of the brachial artery in response to increased blood flow during reactive hyperaemia (flow-mediated dilatation; FMD). Endothelial IR injury was induced by 20 min of upper limb ischaemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. RPostC was induced by applying 2 cycles of 5 minutes ischaemia and 5 minutes reperfusion on the leg during arm ischaemia (via a second blood pressure cuff). In order to determine the dependence of RPostC on autonomic activation, we administered the alpha adrenoceptor blocker phentolamine (0.2– 0.7mg/min, intravenously) during the application of the RPostC stimulus. FMD was determined before ischaemia and at 20 minutes of reperfusion. FMD (percentage change from baseline diameter) was compared statistically by ANOVA. IR alone caused a significant reduction in FMD (5.9±0.7% pre- versus 2.2±0.4% post-IR, n=9, P<0.001). This reduction was prevented by RPostC (5.8±0.4% pre- versus 5.4±0.3% post-IR, n=8, P>0.05). Systemic phentolamine blocked the protective effects of RPostC (FMD 6.1±0.5% pre- versus 2.0±0.3% post-IR, n=7, P<0.001). These data indicate, for the first time in humans, that protection from RPostC depends on preservation of adrenergic signalling. Alpha blockade neutralises one of the endogenous mechanisms of ischemic protection in humans; the clinical consequences of this remain to be determined.

Sequential Limb Ischemia Demonstrates Remote Postconditioning Protection of Murine Skeletal Muscle

2009 ◽  
Vol 123 (Supplement) ◽  
pp. 8S-16S ◽  
Author(s):  
Kyle R. Eberlin ◽  
Michael C. McCormack ◽  
John T. Nguyen ◽  
H Soner Tatlidede ◽  
Mark A. Randolph ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Limb Ischemia ◽  
Murine Skeletal Muscle ◽  
Remote Postconditioning

Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use

2016 ◽  
Vol 88 (8) ◽  
pp. 121-126
Author(s):  
L N Maslov ◽  
S Yu Tsibulnikov ◽  
A V Tsepokina ◽  
M V Khutornaya ◽  
A G Kutikhin ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Multicenter Study ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Abdominal Aortic Aneurysm Repair ◽  
Multicenter Trial ◽  
Remote Postconditioning

The results of experimental and clinical studies strongly suggest that remote ischemic preconditioning (RIP) has no neuroprotective effect during cardiac surgery performed under extracorporeal circulation. Remote preconditioning (RP) has no neuroprotective effect in hemorrhagic stroke. A randomized multicenter study is needed to evaluate the efficiency RIP in patients with ischemic stroke. RP reduces the severity of ischemia/reperfusion kidney injury during transplantation. RIP has been established to prevent contrast-induced nephropathy. There is a need for a multicenter trial to evaluate the efficiency of RIP in patients with abdominal aortic aneurysm repair. Analysis of the presented data indicates that RIP fails to prevent cardiorenal syndrome in infants and children during cardiac surgery. The data available in the literature on the capacity of RIP to provide nephroprotective effect in patients after coronary artery bypass surgery are discordant and indicative of the advisability of a multicenter study.

Cardioprotrective effect of remote postconditioning: Mechanisms and possibilities of clinical application

2016 ◽  
Vol 94 (9) ◽  
pp. 650-656
Author(s):  
Leonid N. Maslov ◽  
S. Yu. Tsibul’nikobv ◽  
A. V. Tsepokina ◽  
M. V. Khutornaya ◽  
A. G. Kutikhin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Coronary Artery Bypass Surgery ◽  
Bypass Surgery ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Transient Ischemia ◽  
Clinical Investigations ◽  
Postinfarction Remodeling ◽  
Remote Postconditioning

Experimental data indicate that postconditioning at a distance is an effective method for cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases a probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning depends on the release of tissue factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion after transient ischemia. Clinical investigations show that postconditioning at a distance is an effective method for the prevention of reperfusion injury of the heart during coronary artery bypass surgery.

Neuroprotection by peripheral nerve electrical stimulation and remote postconditioning against acute experimental ischaemic stroke

2015 ◽  
Vol 37 (5) ◽  
pp. 447-453 ◽  
Author(s):  
Yao Xiao ◽  
Adam Hafeez ◽  
Ying Zhang ◽  
Shimeng Liu ◽  
Qingtao Kong ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Peripheral Nerve ◽  
Ischaemic Stroke ◽  
Remote Postconditioning

scholarly journals PI3K-Akt/eNOS in remote postconditioning induced by brief pulmonary ischemia

2014 ◽  
Vol 37 (1) ◽  
pp. 26 ◽  
Author(s):  
Yan-hua Tang ◽  
Jue-shen Yang ◽  
Hai-yan Xiang ◽  
Jia-jun Xu
Keyword(s):  
Protein Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Serum Levels ◽  
Myocardial Cells ◽  
Akt Inhibitor ◽  
Remote Postconditioning ◽  
Enos Protein Expression ◽  
Enos Protein

Purpose: Postconditioning, a series of brief ischemia-reperfusion sequences given before an ischemic heart undergoes sustained reperfusion, has been shown to lessen ischemia/reperfusion injury. The current study establishes a rabbit model of myocardial ischemia-reperfusion and studied the effects of pulmonary remote postconditioning in this model. Methods: Serum levels of creatine kinase (CK), superoxide dismutase (SOD), and malondialdehyde (MDA), protein expression of endothelial nitric oxide synthase (eNOS), Rho kinase (ROCK- 2), and protein kinase B (Akt) in myocardial cells and the apoptosis index of myocardial cells were examined. Results: Pulmonary remote postconditioning decreased CK, significantly decreased MDA, and increased SOD. Postconditioning significantly increased eNOS protein expression. Administration of eNOS inhibitor, L-NAME, dramatically suppressed the postconditioning-induced eNOS protein expression and serum SOD level, but significantly increased MDA level. The two longer sessions of postconditioning increased Akt, although this increase was not accompanied by changes in levels of the Akt inhibitor, ROCK-2. Blocking eNOS activity with L-NAME had no visible effect on either Akt or ROCK-2. Conclusion: Our results suggest a role for Akt in remote postconditioning-induced myocardial protection, but do not support an involvement of eNOS in Akt-mediated action.

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