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Possible Involvement of Oxidative Stress and Inflammatory Mediators in the Protective Effects of the Early Preconditioning Window Against Transient Global Ischemia in Rats

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Abstract

Ischemic preconditioning (IPC), comprising exposure to sub-lethal short term ischemic events, has been shown to exert adaptive responses in many organs including the brain, thus guarding against exacerbations of ischemia reperfusion (IR). However, the mechanisms involved in the early phase of such a protection remain elusive; hence, the present study aimed to investigate the modulatory effect of preconditioning against IR induced injury on infarct size, free radicals, inflammatory/anti-inflammatory markers, caspase-3 and heat shock protein (HSP)70 in the rat hippocampus. To this end, male Wistar rats were divided into 3 groups, (1) sham operated (SO) control; (2) IPC, animals were subject to 3 episodes of ischemia (5 min) followed by reperfusion (10 min), afterwards rats underwent ischemia (15 min) followed by reperfusion (60 min); (3) IR animals were subjected to 15 min global ischemia followed by 60 min reperfusion. IR produced cerebral infarction accompanied by an imbalance in the hippocampal redox status, neutrophil infiltration, elevation in tumor necrosis factor (TNF)-α and prostaglandin (PG)E2, besides reduction in interleukin (IL)-10 and nitric oxide (NO) levels. IPC reverted all changes except for PGE2; however, neither HSP70 nor caspase-3 expression was altered following IR or IPC. The current study points thus towards the activation of the antioxidant system, anti-inflammatory pathway, as well as NO in the early phase of preconditioning protection.

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Abbreviations

NPSH:

Nonproteinthiols

HSP:

Heat shock protein

IL-10:

Interleukin10

IPC:

Ischemia preconditioning

IR:

Ischemia reperfusion

MDA:

Malondialdehyde

MnSOD:

Manganese superoxide dismutase

MPO:

Myeloperoxidase

NO:

Nitric oxide

PGE2 :

Prostaglandin E2

ROS:

Reactive oxygen species

SO:

Sham operated

TAC:

Total antioxidant capacity

TBARS:

Thiobarbituric acid reactive substances

TNF-α:

Tumor necrosis factor-alpha

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, KasrEl-AiniStr., Cairo, 11562, Egypt

    Noha N. Nassar, Rania M. Abdelsalam & Dalaal M. Abdallah

  2. Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, NC, 27858-4353, USA

    Abdel A. Abdel-Rahman

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  1. Noha N. Nassar
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Correspondence to Dalaal M. Abdallah.

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Nassar, N.N., Abdelsalam, R.M., Abdel-Rahman, A.A. et al. Possible Involvement of Oxidative Stress and Inflammatory Mediators in the Protective Effects of the Early Preconditioning Window Against Transient Global Ischemia in Rats. Neurochem Res 37, 614–621 (2012). https://doi.org/10.1007/s11064-011-0651-7

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