Protective Effect of Ischemia Preconditioning of Lower Limbs on Brain Ischemia-reperfusion Injury via Neural Pathways

YU Chao, LIU Jin

Abstract

To explore if ischemia preconditioning of lower limbs could protect the local ischemia reperfusion damage in rat brain and the role of neural pathways during the process. Methods Fifty male Sprague-Dawley rats were randomly assigned into five groups (n=10 for each group). Group Ⅰ was sham group. Group Ⅱ was the occlusion of middle cerebral artery (MCAO) for 90 min. Group Ⅲ was remote ischemic preconditioning (RIPC) 24 h before MCAO. Group Ⅳ was femoral nerve and sciatic nerve (FS) resected before RIPC and MCAO. Group Ⅴ was FS resected only before MCAO. All the rats in the later four groups were subjected to brain reperfusion after MCAO for 90 min. The brain samples were harvested 24 h after MCAO for the evaluation of neuroligical deficit score (NDS) and infarct volume, histomorphlogical study with HE staining, as well as the evaluation of neuron apoptosis with TUNEL staining and Caspase-3 staining. Results The infarct volume in group RIPC+MCAO （18.24%） was smaller than that in MCAO group (30.92%), and TUNEL and Caspase-3 staining also demonstrated significantly lesser apoptotic neurons (20.81, 5.78) in comparison with MCAO group (45.23, 12.94). However, the infarct volume (28.77%) and apoptotic neurons (53, 11.83) of FS+ RIPC +MCAO group did not show statistical difference when compared with those of MCAO group. The results of NDS and HE staining in RIPC+MCAO group were better than those in MCAO group, while they showed no statistical difference in the condition of nerve resected before RIPC+MCAO when compared with MCAO group. Conclusion The ischemia preconditioning of lower limbs may provide protection on ischemia-reperfusion injury in rats brain through neural pathways.

 

Keywords: Ischemia preconditioning, Brain ischemia, Cerebral protection 

 

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References


Murry CE. Jennings RB, Reimer К A. Preconditioning with ischemia; a delay of lethal cell injury in ischemic myocardium. Circulation, 1986; 74(5); 1124-1136.

Przyklenk K. Bauer B, Ovize M, et al. Regional ischemic preconditioning ' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993; 87 (3) ;893-899.

Jensen HA,Loukogeorgakis S, Yannopoulos F. et al. Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest. Circulation, 2011; 123 ( 7): 714- 721.

Hajrasouliha AR, Tavakoli S,Ghasemi M, et al. Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB2 receptors in the rat heart. Eur J Pharmacol, 2008? 579(1-3): 246-252.

Kanoria S, Jalan R, Davies NA, et al. Remote ischemic preconditioning of the hind limb reduces experimental liver warm ischemia reperfusion injury. Br J Surg, 2006 ; 93( 6) : 762- 768.

Heidbreder M, Naumann A,Tempel К,et al. Remote ischemic preconditioning: the differential role of mitogen activated protein kinase pathways. Cardiovasc Res, 2008; 78 ( 1 ); 108- 115.

Oehmann C, Benz S.Drognitz О,et al. Remote preconditioning reduces microcirculatory disorders in pancreatic ischemia reperfusion injury. Pancreas, 2007;35(4) ;45-50.

Loukogeorgakis SP. Panagiotidou AT, Broadhead MW .et al. Remote ischemic preconditioning provides early and late protection against endothelial ischemia reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol, 2005; 46(3); 450-456.

Jan WC, Chen CH, Tsai PS. Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shockvresuscitation in rats. Resuscitation,2011;82(6) :760-766.

Kitagawa K, Matsumoto M, Tagaya M. ‘Ischemic tolerance’ phenomenon found in the brain. Brain Res, 1990;528( 1 ); 21- 24.

Zhao HG, Li WB, Li QJ. Limb ischemic preconditioning attenuates apoptosis of pyramidal neurons in the CA1 hippocampus induced by cerebral ischemia-reperfusion in rats. Acta Physiologica Sinica,2004 ; 56(1); 407-412.

Weinbrenner C, Nelles M, Herzog N, et al. Remote preconditioning by infrarenal occlusion of theorta protects the heart from infarction; a newly identified non-neuronal but PKC dependent pathway. Cardiovasc Res,2002;55(3):590-601.

Malhotra S, Savitz SI, Ocava L,et al. Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. Neurosci Res, 2006;83(1): 19-27.

Huang Z, Huang PL, Panahian N, et al. Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science, 1994 ;265(5180) ;883-1885.

Malhotraa S, Naggarb I. Stewart M, et al. Neurogenic pathway mediated remote preconditioning protects the brain from transient focal ischemic injury. Brain Res. 2011; 1386: 184-190.

Ren C, Gao X, Steinberg GK, et al. Limb remote preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Neuroscience,2008; 151(4): 1099-1103.

Lim SY, Yellon DM, Hausenloy DJ, et al. The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res Cardiol,2010; 105(5) ;651-655.

Koch S, Katsnelson M, Dong C,et al. Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase lb study of safety and feasibility. Stroke,2011;42(9); 1387-1391.

Walsh SR, Nouraei SA, Tang TY, et al. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy; results from a pilot randomized clinical trial. Vase Endovascular Surg,2010;44(6) :434-439.

Zhao HG, Sun XC, Xian XH, et al. The role of nitric oxide in the neuroprotection of limb ischemic preconditioning in rats. Neurochem Res,2007 ;32( 11): 1919-1926.


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