Chenju YI, Haidong GUO, Qiangqiang LIU, Li WANG, Hongxia LI, Ce XU

Limb remote ischemic postconditioning is effective but also time-course-limited in protecting the brain from I/R injury

To determine the effect of limb remote ischemic postconditioning (LIPoC) against cerebral ischemia reperfusion in rats and the relationship between cycle number or remote postconditioning episode duration and the protective function of LIPoC. Materials and methods: Transient focal ischemia/reperfusion was induced by 90 min of middle cerebral artery occlusion (MCAO) with nylon monofilament and 22 h of reperfusion in male Sprague-Dawley rats. The animals underwent LIPoC consisting of 1, 2, or 3 cycles, with each occlusion or release lasting for 5 min (5/5), 10 min (10/10), or 15 min (15/15) of bilateral femoral artery occlusion/release. Neurological score, infarct volume, water content, blood-brain barrier permeability (BBB), neuronal analysis, immunohistochemical detection, and mitochondrial permeability transition pore opening were measured. Results: Infarct volume was significantly reduced in the groups with 2 cycles of 15/15, 3 cycles of 10/10, and 2 cycles of 10/10. These 3 groups also had attenuated brain edema, BBB disruption, and apoptosis compared to both the MCAO and sham groups. Conclusion: This study affirmed the protective effect of LIPoC on cerebral reperfusion injury. Furthermore, it indicated that the accumulative time of limb occlusion/reperfusion might be crucial in remote postconditioning and that LIPoC exerted its maximum protective effect if the accumulative time of limb occlusion/reperfusion lasted from 40 to 60 min.

Anahtar Kelimeler:

Key words: Stroke, ischemia/reperfusion injury, middle cerebral artery occlusion, remote ischemic postconditioning, limb, rat

Limb remote ischemic postconditioning is effective but also time-course-limited in protecting the brain from I/R injury

Keywords:

Key words: Stroke, ischemia/reperfusion injury, middle cerebral artery occlusion, remote ischemic postconditioning, limb, rat,

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Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet 2008; 371: 1612-3.
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124-6. 3 . Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ et al. Remote postconditioning. Brief renal ischemia and reperfusion
applied before coronary artery reperfusion reduces myocardial
infarct size via endogenous activation of adenosine receptors.
Basic Res Cardiol 2005; 100: 404-12.
Eberlin KR, McCormack MC, Nguyen JT, Tatlidede HS, Randolph MA, Austen WG Jr et al. Sequential limb ischemia demonstrates remote postconditioning protection of murine skeletal muscle. Plast Reconstr Surg 2009; 123: 8S-16S.
Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ et al. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation 2007; 116: 1386-95.
0. Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 1986; 8: 1-8.
1. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20: 84-91. 1 2. Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM et al. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantifi cation of experimental cerebral infarction in rats. Stroke 1986; 17: 1304
3. Demediuk P, Lemke M, Faden AI. Spinal cord edema and changes in tissue content of Na+, K+, and Mg2+ aft er impact trauma in rats. Adv Neurol 1990; 52: 225-32.
4. Kaya M, Kalayci R, Küçük M, Arican N, Elmas I, Kudat H et al. Eff ect of losartan on the blood-brain barrier permeability in diabetic hypertensive rats. Life Sci 2003; 73: 3235-44.
Clark JB, Nicklas WJ. Th e metabolism of rat brain mitochondria. Preparation and characterization. J Biol Chem 1970; 245: 4724- 31.
Takuma K, Phuagphong P, Lee E, Mori K, Baba A, Matsuda T et al. Anti-apoptotic eff ect of cGMP in cultured astrocytes: inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore. J Biol Chem 2001; 276: 48093-9.
Matsubara T, Minatoguchi S, Matsuo H, Hayakawa K, Segawa T, Matsuno Y et al. Th ree minute, but not one minute, ischemia and nicorandil have a preconditioning eff ect in patients with coronary artery disease. J Am Coll Cardiol 2000; 35: 345-51.
Yang XM, Philipp S, Downey JM, Cohen MV. Postconditioning’s protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation. Basic Res Cardiol 2005; 100: 57-63.
White BC, Sullivan JM, DeGracia DJ, O’Neil BJ, Neumar RW, Grossman LI et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 2000; 179: 1-33.
Gartshore G, Patterson J, Macrae IM. Infl uence of ischemia and reperfusion on the course of brain tissue swelling and blood- brain barrier permeability in a rodent model of transient focal cerebral ischemia. Exp Neurol 1997; 147: 353-60.
Davoli MA, Fourtounis J, Tam J, Xanthoudakis S, Nicholson D, Robertson GS et al. Immunohistochemical and biochemical assessment of caspase-3 activation and DNA fragmentation following transient focal ischemia in the rat. Neuroscience 2002; 115: 125-36.
Burley DS, Ferdinandy P, Baxter GF. Cyclic GMP and protein kinase-G in myocardial ischaemia-reperfusion: opportunities and obstacles for survival signaling. Br J Pharmacol 2007; 152: 855-69.