Exercise pre‑conditioning alleviates brain damage via excitatory amino acid transporter 2 and extracellular signal‑regulated kinase 1/2 following ischemic stroke in rats

Wang,Xiao; Zhang,Min; Feng,Rui; Li,Wen‑Bin; Ren,Shi‑Qing; Zhang,Feng

doi:10.3892/mmr.2014.2834

Exercise pre‑conditioning alleviates brain damage via excitatory amino acid transporter 2 and extracellular signal‑regulated kinase 1/2 following ischemic stroke in rats

Authors:
- Xiao Wang
- Min Zhang
- Rui Feng
- Wen‑Bin Li
- Shi‑Qing Ren
- Feng Zhang
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Affiliations: Department of Neurology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China, Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
Published online on: October 31, 2014 https://doi.org/10.3892/mmr.2014.2834
Pages: 1523-1527

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Abstract

Previous studies have reported that physical exercise may exert a neuroprotective effect in humans as well as animals. However, the detailed mechanisms underlying the neuroprotective effect of exercise has remained to be elucidated. The aim of the present study was to explore the possible signaling pathways involved in the protective effect of pre‑ischemic treadmill training for ischemic stroke in rats. A total of 36 male Sprague‑Dawley rats were divided at random into three groups as follows (n=12 for each): Sham surgery group; middle cerebral artery occlusion (MCAO) group; and exercise with MCAO group. Following treadmill training for three weeks, the middle cerebral artery was occluded for 90 min in order to induce ischemic stroke, followed by reperfusion. Following 24 h post‑reperfusion, six rats from each group were assessed for neurological deficits and then sacrificed to calculate the infarct volume. The remaining rats (n=6 for each group) were sacrificed and the expression levels of excitatory amino acid transporter 2 (EAAT‑2) and extracellular signal‑regulated kinase 1/2 (ERK1/2) were detected using western blot analysis. The results of the present study demonstrated that rats that underwent pre‑ischemic exercise intervention had a significantly decreased brain infarct volume and neurological deficits; in addition, the pre‑ischemic exercise group showed decreased overexpression of phosphorylated ERK1/2 and increased expression of EAAT‑2 following ischemic stroke. In conclusion, treadmill training exercise prior to ischemic stroke alleviated brain damage in rats via regulation of EAAT‑2 and ERK1/2.

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1	Stummer W, Baethmann A, Murr R, et al: Cerebral protection against ischemia by locomotor-activity in gerbils. Underlying mechanisms. Stroke. 26:1423–1429. 1995. View Article : Google Scholar
2	Ang ET, Wong PTH, Moochhala S and Ng YK: Neuroprotection associated with running: is it a result of increased endogenous neurotrophic factors? Neuroscience. 118:335–345. 2003. View Article : Google Scholar : PubMed/NCBI
3	Endres M, Gertz K, Lindauer U, et al: Mechanisms of stroke protection by physical activity. Ann Neurol. 54:582–590. 2003. View Article : Google Scholar : PubMed/NCBI
4	Li J, Luan XD, Clark JC, et al: Neuroprotection against transient cerebral ischemia by exercise pre-conditioning in rats. Neurol Res. 26:404–408. 2004. View Article : Google Scholar : PubMed/NCBI
5	Ding YH, Ding Y, Li J, et al: Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model. Neurol Res. 28:184–189. 2006. View Article : Google Scholar : PubMed/NCBI
6	Guyot LL, Diaz FG, O’Regan MH, McLeod S, Park H and Phillis JW: Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model. Neurosci Lett. 299:37–40. 2001. View Article : Google Scholar : PubMed/NCBI
7	Zhang F, Jia J, Wu Y, Hu Y and Wang Y: The effect of treadmill training pre-exercise on glutamate receptor expression in rats after cerebral ischemia. Int J Mol Sci. 11:2658–2669. 2010. View Article : Google Scholar : PubMed/NCBI
8	Zhang F, Wu Y, Jia J and Hu YS: Pre-ischemic treadmill training induces tolerance to brain ischemia: involvement of glutamate and ERK1/2. Molecules. 15:5246–5257. 2010. View Article : Google Scholar : PubMed/NCBI
9	Beart PM and O’Shea RD: Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br J Pharmacol. 150:5–17. 2007. View Article : Google Scholar
10	Suchak SK, Baloyianni NV, Perkinton MS, Williams RJ, Meldrum BS and Rattray M: The ‘glial’ glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings. J Neurochem. 84:522–532. 2003. View Article : Google Scholar : PubMed/NCBI
11	Liebelt B, Papapetrou P, Ali A, et al: Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular signal-regulated-kinase 1/2. Neuroscience. 166:1091–1100. 2010. View Article : Google Scholar : PubMed/NCBI
12	Lu ZM and Xu SC: ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 58:621–631. 2006. View Article : Google Scholar : PubMed/NCBI
13	Alessandrini A, Namura S, Moskowitz MA and Bonventre JV: MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc Natl Acad Sci USA. 96:12866–12869. 1999. View Article : Google Scholar : PubMed/NCBI
14	Namura S, Iihara K, Takami S, et al: Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc Natl Acad Sci USA. 98:11569–11574. 2001. View Article : Google Scholar : PubMed/NCBI
15	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
16	Ding YH, Ding Y, Li J, Bessert DA and Rafols JA: Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model. Neurol Res. 28:184–189. 2006. View Article : Google Scholar : PubMed/NCBI
17	National Center for Health Statistics. Health, United States, 2010: With Special Feature on Death and Dying. Hyattsville (MD, USA): 2011
18	Krarup LH, Truelsen T, Gluud C, et al: ExStroke Pilot Trial Group: Prestroke physical activity is associated with severity and long-term outcome from first-ever stroke. Neurology. 71:1313–1318. 2008. View Article : Google Scholar : PubMed/NCBI
19	Hinzman JM, Thomas TC, Quintero JE, Gerhardt GA and Lifshit J: Disruptions in the regulation of extracellular glutamate by neurons and glia in the rat striatum two days after diffuse brain injury. J Neurotrauma. 29:1197–1208. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kanai Y and Hediger MA: The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflugers Arch. 447:469–479. 2004. View Article : Google Scholar
21	Verma R, Mishra V, Sasmal D and Raghubir R: Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury. Eur J Pharmacol. 638:65–71. 2010. View Article : Google Scholar : PubMed/NCBI
22	Tanaka K, Watase K, Manabe T, et al: Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 276:1699–1702. 1997. View Article : Google Scholar : PubMed/NCBI