Skip to main content
SpringerLink
Log in

Treadmill pre-training suppresses the release of glutamate resulting from cerebral ischemia in rats

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

This study was designed to investigate the neuroprotective effect of treadmill pre-training against the over-release of glutamate resulting from cerebral ischemia. Sprague–Dawley rats underwent 2 weeks of treadmill run-training before cerebral ischemia was performed by middle cerebral artery occlusion. The level of glutamate in brain extracellular fluid was detected before, during and after ischemia/reperfusion. The expression of metabotropic glutamate receptor-1 (mGluR1) mRNA in striatum was examined after ischemia for 80 min and reperfusion for 240 min. Neurological defect score and brain infarction volumes were measured. The treadmill pre-training significantly suppressed the release of glutamate, and reduced the expression of mGluR1 mRNA at 59% (P < 0.01) and 62% (P < 0.05), respectively, as compared with the ischemia group. The neurological defect score and infarction volume were significantly improved by 75% (P < 0.01) and 74% (P < 0.01), respectively, in the pre-training group, as compared to the ischemia group. Treadmill pre-training has a significant neuroprotective function against ischemia/reperfusion injury, by suppressing glutamate release resulting from cerebral ischemia, and this effect may be mediated by downregulation of mGluR1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bao WL, Williams AJ, Faden AI, Tortella FC (2001) Selective mGluR5 receptor antagonist or agonist provides neuroprotection in a rat model of focal cerebral ischemia. Brain Res 922:173–179

    Article  CAS  PubMed  Google Scholar 

  • Baskys A, Bayazitov I, Fang L, Blaabjerg M, Poulsen FR, Zimmer J (2005) Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesis. Neuropharmacology 49(Suppl 1):146–156

    Article  CAS  PubMed  Google Scholar 

  • Bicalho AF, Guatimosim C, Prado MA, Gomez MV, Romano-Silva MA (2002) Investigation of the modulation of glutamate release by sodium channels using neurotoxins. Neuroscience 113:115–123

    Article  CAS  PubMed  Google Scholar 

  • Bonde C, Noraberg J, Noer H, Zimmer J (2005) Ionotropic glutamate receptors and glutamate transporters are involved in necrotic neuronal cell death induced by oxygen-glucose deprivation of hippocampal slice cultures. Neuroscience 136:779–794

    Article  CAS  PubMed  Google Scholar 

  • Chong ZZ, Kang J, Li F, Maiese K (2005) mGluRI targets microglia activation and selectively prevents neuronal cell engulfment through Akt and caspase dependent pathways. Curr Neurovasc Res 2:197–211

    Article  CAS  PubMed  Google Scholar 

  • Eweka AO, Eweka A, Om’Iniabohs FAE (2010) Histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female Wistar rats. North Am J Med Sci 2:146–149

    Google Scholar 

  • Fairman WA, Vandenberg RJ, Arriza JL, Kavanaugh MP, Amara SG (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375:599–603

    Article  CAS  PubMed  Google Scholar 

  • Fujimoto S, Katsuki H, Kume T, Kaneko S, Akaike A (2004) Mechanisms of oxygen glucose deprivation-induced glutamate release from cerebrocortical slice cultures. Neurosci Res 50:179–187

    Article  CAS  PubMed  Google Scholar 

  • Guyot LL, Diaz FG, O’Regan MH, Mcleod S, Park H, Phillis JW (2001) 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

    Article  CAS  PubMed  Google Scholar 

  • Hediger MA, Welbourne TC (1999) Introduction: glutamate transport, metabolism, and physiological responses. Am J Physiol Renal Physiol 277:477–480

    Google Scholar 

  • Henrich-Noack P, Flor PJ, Sabelhaus CF, Prass K, Dirnagl U, Gasparini F, Sauter A, Rudin M, Reymann KG (2000) Distinct influence of the group III metabotropic glutamate receptor agonist (R, S)-4-phosphonophenylglycine [(R, S)-PPG]on different forms of neuronal damage. Neuropharmacology 39:911–917

    Article  CAS  PubMed  Google Scholar 

  • Hu YS, Jia J, Wu Y, Yu HX, Cao ZJ, Xia CM (2008) The effect of treadmill pre-training on the brain protection in rat’s cerebral infarction with the excitatory amino acid neurotransmitter dynamic changes. Chin J Physici Med Rehab 23:364–367

    Google Scholar 

  • Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz M (1994) Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthases. Science 265:1883–1885

    Article  CAS  PubMed  Google Scholar 

  • Hwang I, Lee JC, Yoo KY, Cho JH, Jung JY, Kang TC, Oh YS, Kim WK, Won M (2007) Transient ischemia-induced changes of excitatory amino acid carrier 1 in the ventral horn of the lumbar spinal cord in rabbits. Neurol Res 29(3):310–316

    Article  PubMed  Google Scholar 

  • Jia J, Hu YS, Wu Y (2008) Effects of treadmill pre-training on the glutamate levels of dynamic change after cerebral infarction in rat’s brain. Chin J Physici Med Rehab 30:465–468

    Google Scholar 

  • Kanai Y, Hediger MA (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471

    Article  CAS  PubMed  Google Scholar 

  • Keyvani K, Bosse F, Reinecke S (2001) Postlesional transcriptional regulation of metabotropic glutamate receptors: implications for plasticity and excitotoxicity. Acta Neuropathol 101:79–84

    CAS  PubMed  Google Scholar 

  • Kohara A, Takahashi M, Yatsugi S, Tamura S, Shitaka Y, Hayashibe S, Kawabata S, Okada M (2008) Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models. Brain Res 1191:168–179

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Lee J, Choi KY, Hepp R, Lee JY, Lim MK, Chatani-Hinze M, Roche PA, Kim DG, Ahn YS, Kim CH, Roche KW (2008). Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. Proc Natl Acad Sci USA 26: 105(34):12575–12580

    Google Scholar 

  • Lin CL, Bristol LA, Jin L, Dykes-Hoberg M, Crawford T, Clawson L, Rothstein JD (1998) Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 20:589–602

    Article  CAS  PubMed  Google Scholar 

  • Lombard VAR (1996) Determination of glutamate decarboxylase by high-performance liquid chromatography. J Chromatograph B 681:63–67

    Article  Google Scholar 

  • Longa EZ, Weinstein PR, Carlson S, Cummmins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    CAS  PubMed  Google Scholar 

  • Martin LJ, Sieber FE, Traystman RJ (2000) Apoptosis and necrosis occur in separate neuronal populations in hippocampus and cerebellum after ischemia and are associated with differential alterations in metabotropic glutamate receptor signaling pathways. J Cereb Blood Flow Metab 20:153–167

    Article  CAS  PubMed  Google Scholar 

  • Mennerick S, Zorumski CF (1994) Glial contributions to excitatory neurotransmission in cultured hippocampal cells. Nature 368:59–62

    Article  CAS  PubMed  Google Scholar 

  • Mironov SL (2008) Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice. J Physiol 586:2277–2291

    Article  CAS  PubMed  Google Scholar 

  • Nicoletti F, Battaglia G, Storto M, Ngomba RT, Iacovelli L, Arcella A, Gradini R, Sale P, Rampello L, Vita TD, Marco RD, Melchiorri D, Bruno V (2007) Metabotropic glutamate receptors: beyond the regulation of synaptic transmission. Psychoneuroendocrinology 32(Suppl 1):S40–S45

    Article  CAS  PubMed  Google Scholar 

  • Otis TS, Kavanaugh MP, Jahr CE (1997) Postsynaptic glutamate transport at the climbing fiber-Purkinje cell synapse. Science 277:1515–1518

    Article  CAS  PubMed  Google Scholar 

  • Parelkar NK, Wang JQ (2008) Upregulation of metabotropic glutamate receptor 8mRNA expression in the rat forebrain after repeated amphetamine administration. Neurosce Lett 433:250–254

    Article  CAS  Google Scholar 

  • Picca MP, Attucci S, Cuziz A, Peruginelli F, Moroni F, Pellegrini-Giampiettro DDE (2002) Activation of mGlu1 but not mGlu5 metabotropic glutamate receptors contributes to postischemic neuronal injury in vitro and vivo. Pharmacol Biochem Behav 73:439–442

    Article  PubMed  Google Scholar 

  • Pines G, Danbolt NC, Bjoras M, Zhang Y, Bendahan A, Eide L, Koepsell H, Storm-Mathisen J, Seeberg E, Kanner BI (1992) Cloning and expression of a rat brain L-glutamate transporter. Nature 360:464–467

    Article  CAS  PubMed  Google Scholar 

  • Ponce J, de la Ossa NP, Hurtado O, Millan M, Marenillas JF, Davalos A, Gasull T (2008) Simvastatin reduces the association of NMDA receptors to lipid rafts: a cholesterol-mediated effect in neuroprotection. Stroke 39:1269–1275

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Dykes-Hoberg M, Pardo CA et al (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686

    Article  CAS  PubMed  Google Scholar 

  • Sommer C, Roth SU, Kuhn R, Kiessling M (2000) Metabotropic glutamate receptor subtypes are differentially expressed after transient cerebral ischemia without, during and after tolerance induction in the gerbil hippocampus. Brain Res 872:172–180

    Article  CAS  PubMed  Google Scholar 

  • Storck T, Schulte S, Hofmann K, Stoffel W (1992) Structure, expression, and functional analysis of a Na(1)-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci USA 89:10955–10959

    Article  CAS  PubMed  Google Scholar 

  • Surin A, Pshenichkin S, Grajkowaska E, Surina E, Wroblewski JT (2007) Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists. Neuropharmacology 52:744–754

    Article  CAS  PubMed  Google Scholar 

  • Tabata T, Kawakami D, Hashimoto K, Kassai H, Yoshida T, Hashimotodani Y, Fredholm BB, Sekino Y, Aiba A, Kano M (2007) G protein-independent neuromodulatory action of adenosine on metabotropic glutamate signaling in mouse cerebellar Purkinje cells. J Physiol 581:693–708

    Article  PubMed  Google Scholar 

  • Tanaka K, Watase K, Manabe T et al (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276:1699–1702

    Article  CAS  PubMed  Google Scholar 

  • Wang RY, Yang YR, Yu SM (2001) Protective effects of treadmill training on infarction in rats. Brain Res 922:140–143

    Article  CAS  PubMed  Google Scholar 

  • Xi ZX, Shen H, Baker DA, Kalivas PW (2003) Inhibition of non vesicular glutamate release by group III metabotropic glutamate receptors in the nucleus accumbens. J Neurochem 87:1204–1212

    Article  CAS  PubMed  Google Scholar 

  • Yawata I, Takeuchi H, Doi Y, Liang J, Mizuno T, Suzumura A (2008) Macrophage-induced neurotoxicity is mediated by glutamate and attenuated by glutaminase inhibitors and gap junction inhibitors. Life Sci 82:1111–1116

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Xiong L, Hu W, Zheng Y, Zhu Z, Liu Y, Chen S, Wang X (2004) Preconditioning with prolonged oxygen exposure induces ischemic tolerance in the brain via oxygen free radical formation. Can J Aesth 51:258–265

    Article  Google Scholar 

  • Zhang Y, Su M, Qin JX (2005) The mRNA changes of metabotropic glutamate receptor 1 (mGluRl) and metabotropic glutamate receptor 5 (mGluR5) in rats with focal cerebral ischemia and reperfusion. J Brain Nervous Dis 13:264–266

    CAS  Google Scholar 

Download references

Acknowledgments

The present study was supported by the National High Technology Research and Development Program of China (No. 2007AA02Z482) and National Natural Science Foundation of China (No. 30772300).

Author information

Authors and Affiliations

  1. Department of Rehabilitation, Huashan Hospital, Fudan University, Shanghai, China

    Jie Jia, Yong-Shan Hu, Hui-Xian Yu & Gang Liu

  2. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China

    Jie Jia, Yong-Shan Hu & Yi Wu

  3. Department of Physiology and Pathophysiology, Fudan University Medical College, Shanghai, China

    Da-Nian Zhu & Chun-Mei Xia

  4. Fudan University Pharmacy College, Shanghai, China

    Zhi-Juan Cao

  5. Department of Rehabilitation, Third Hospital, Xinxiang Medical College, Xinxiang, Henan, China

    Xi Zhang & Qing-Chuan Guo

Authors
  1. Jie Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-Shan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui-Xian Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Da-Nian Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun-Mei Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhi-Juan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qing-Chuan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong-Shan Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jia, J., Hu, YS., Wu, Y. et al. Treadmill pre-training suppresses the release of glutamate resulting from cerebral ischemia in rats. Exp Brain Res 204, 173–179 (2010). https://doi.org/10.1007/s00221-010-2320-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-010-2320-5

Keywords

Search

Navigation