‘Ischemic tolerance’ phenomenon detected in various brain regions

Kitagawa, Kazuo; Matsumoto, Masayasu; Kuwabara, Kosuke; Tagaya, Masayoshi; Ohtsuki, Toshiho; Hata, Ryuji; Ueda, Hirokazu; Handa, N.; Kimura, Kazufumi; Kamada, Takenobu

doi:10.1016/0006-8993(91)91596-s

Cited by 314 publications

(169 citation statements)

References 25 publications

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“…This phenomenon has now been documented across many different organs and species [5,11,[33][34][35][36]. Our previous study (unique identifier: NCT01321749) showed that BAIPC safely and effectively reduced the incidence of stroke recurrence in symptomatic IAS patients younger than 81 years of age [14,18].…”

Section: Discussionmentioning

confidence: 85%

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

et al. 2015

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Symptomatic intracranial arterial stenosis (SIAS) is very common in octo-and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80 years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo-and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo-and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n=30) underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion for 5 min each twice daily. Those in the control group (n=28) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30 days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180 days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p<0.01). In 180 days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p<0.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo-and nonagenarians with SIAS. A multicenter trial is ongoing.Clinical Trial Registration: www.clinicaltrials.gov, unique identifier: NCT01570231.

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Section: Discussionmentioning

confidence: 85%

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

et al. 2015

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“…Ischemic tolerance is a well known phenomenon in which brief ischemic insults (ischemic preconditioning) confer robust neuroprotection to hippocampal CA1 neurons against a subsequent severe ischemic challenge (Kirino et al, 1991;Kitagawa et al, 1991;Liu et al, 1992;Nishi et al, 1993;Simon et al, 1993;Wu et al, 2001). Ischemic tolerance can also be induced in vivo by spreading depression (Kawahara et al, 1997), hypoxia (Gidday et al, 1999), activation of A1 adenosine receptors (Heurteaux et al, 1995), and inhibition of oxidative phosphorylation (Riepe et al, 1997) and in vitro by exposure to excitotoxins (Grabb and Choi, 1999).…”

Section: Introductionmentioning

confidence: 99%

Ischemic Preconditioning: Neuronal Survival in the Face of Caspase-3 Activation

et al. 2004

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Apoptosis is an evolutionarily conserved process critical to tissue development and tissue homeostasis in eukaryotic organisms and, when dysregulated, causes inappropriate cell death. Global ischemia is a neuronal insult that induces delayed cell death with many features of apoptosis. Ischemic preconditioning affords robust protection of CA1 neurons against a subsequent severe ischemic challenge. The molecular mechanisms underlying ischemic tolerance are unclear. Here we show that ischemia induces pronounced caspase-3 activity in naive neurons that die and in preconditioned neurons that survive. Preconditioning intervenes downstream of proteolytic processing and activation of caspase-3 (a protease implicated in the execution of apoptosis) and upstream of the caspase-3 target caspase-activated DNase (CAD, a deoxyribonuclease that catalyzes DNA fragmentation) to arrest neuronal death. We further show that global ischemia promotes expression of the pro-survival inhibitor-of-apoptosis (IAP) family member cIAP, but unleashes Smac/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI), a factor that neutralizes the protective actions of IAPs and promotes neuronal death. Preconditioning blocks the mitochondrial release of Smac/DIABLO, but not the ischemiainduced upregulation of IAPs. In the absence of Smac/DIABLO, cIAP halts the caspase death cascade and arrests neuronal death. These findings suggest that preconditioning preserves the integrity of the mitochondrial membrane, enabling neurons to survive in the face of caspase activation.

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“…Variations in ischemic depolarization times are evident between hippocampi in the same animal, and between ipsilateral cortex and hippocampus (data not shown), so that individual measurements in each region of interest are essential. The predictable relationship between tolerance and depolarization suggests that differences in the severity of priming insults account for most of the variability observed in previous tolerance studies2) 3). While it is difficult to produce a specific depolarization interval in a given hippocampus, maximum tolerance is observed over a broad enough range that tolerant animals can be produced in sufficient numbers for most studies.…”

Section: Discussionmentioning

confidence: 95%

Gene Expression and the Response to Ischemic Insults in Brain: Studies in a Gerbil Model of Induced Tolerance.

Nowak¹,

Abé

1995

Jpn. J. Stroke

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Brief ischemic insults protect against injury following subsequent longer and otherwise damaging periods of ischemia, although such protective effects have usually been quite variable. Selective changes in gene expression are considered good candidates for mediators of the tolerance phenomenon, and the stress protein, hsp72, has received considerable attention in this regard. In recent experiments we have monitored the interval of ischemic depolarization following brief periods of occlusion and have identified depolarization thresholds for tolerance, for injury and for various changes in gene expression. While hsp72 is clearly inducible after moderate insults that do not injure neurons, our results indicate that neuronal protection can be achieved by even milder insults that do not appreciably induce hsp72, but that do induce immediate-early genes of the Fos and Jun families with lower depolarization thresholds. In addition, these studies provide the basis for a reproducible model in which mechanisms of tolerance can be further studied.

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‘Ischemic tolerance’ phenomenon detected in various brain regions

Cited by 314 publications

References 25 publications

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment

Ischemic Preconditioning: Neuronal Survival in the Face of Caspase-3 Activation

Gene Expression and the Response to Ischemic Insults in Brain: Studies in a Gerbil Model of Induced Tolerance.

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