Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC)-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1) protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.
Goldstein, L.B.; Bushnell, C.D.; Adams, R.J.; Appel, L.J.; Braun, L.T.; Chaturvedi, S.; Creager, M.A.; Culebras, A.; Eckel, R.H.; Hart, R.G.; et al. Guidelines for the primary prevention of stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011, 42, 517–584.
Guyot, L.L.; Diaz, F.G.; O’Regan, M.H.; McLeod, S.; Park, H.; Phillis, J.W. 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 2001, 299, 37–40.
Hinzman, J.M.; Thomas, T.C.; Quintero, J.E.; Gerhardt, G.A.; Lifshitz, J. Disruptions in the regulation of extracellular glutamate by neurons and glia in the rat striatum two days after diffuse brain injury. J. Neurotrauma 2012, 29, 1197–1208.
Jia, J.; Hu, Y.S.; Wu, Y.; Liu, G.; Yu, H.X.; Zheng, Q.P.; Zhu, D.N.; Xia, C.M.; Cao, Z.J. Pre-ischemic treadmill training affects glutamate and gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral ischemia. Life Sci 2009, 84, 505–511.
Liu, A.J.; Hu, Y.Y.; Li, W.B.; Xu, J.; Zhang, M. Cerebral ischemic pre-conditioning enhances the binding characteristics and glutamate uptake of glial glutamate transporter-1 in hippocampal CA1 subfield of rats. J. Neurochem 2011, 119, 202–209.
Kawahara, K.; Kosugi, T.; Tanaka, M.; Nakajima, T.; Yamada, T. Reversed operation of glutamate transporter GLT-1 is crucial to the development of preconditioning-induced ischemic tolerance of neurons in neuron/astrocyte co-cultures. Glia 2005, 49, 349–359.
Zhang, M.; Li, W.B.; Geng, J.X.; Li, Q.J.; Sun, X.C.; Xian, X.H.; Qi, J.; Li, S.Q. The upregulation of glial glutamate transporter-1 participates in the induction of brain ischemic tolerance in rats. J. Cereb Blood Flow Metab 2007, 27, 1352–1368.
Münch, C.; Zhu, B.G.; Leven, A.; Stamm, S.; Eink？rn, H.; Schwalenst？cker, B.; Ludolph, A.C.; Riepe, M.W.; Meyer, T. Differential regulation of 5′ splice variants of the glutamate transporter EAAT2 in an in vivo model of chemical hypoxia induced by 3-nitropropionic acid. J. Neurosci. Res 2003, 71, 819–825.
Pow, D.V.; Naidoo, T.; Lingwood, B.E.; Healy, G.N.; Williams, S.M.; Sullivan, R.K.P.; O’Driscoll, S.; Colditz, P.B. Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain. Dev. Brain Res 2004, 153, 1–11.
Bullitt, E.; Rahman, F.N.; Smith, J.K.; Kim, E.; Zeng, D.; Katz, L.M.; Marks, B.L. The effect of exercise on the cerebral vasculature of healthy aged subjects as visualized by MR angiography. AJNR Am. J. Neuroradiol 2009, 30, 1857–1863.
Benedek, A.; Móricz, K.; Jurányi, Z.; Gigler, G.; Lévay, G.; Hársing, L.G., Jr; Mátyus, P.; Szénási, G.; Albert, M. Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats. Brain Res. 2006, 1116, 159–165.