Skip to main content

Advertisement

SpringerLink
Log in

Tiagabine and vigabatrin reduce the severity of NMDA-induced excitotoxicity in chick retina

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

Abstract

The possible neuroprotective effects of two GABAergic drugs, tiagabine (TGB) and vigabatrin (VGB), against N-methyl-d-aspartate (NMDA)-induced excitotoxicity have been investigated in the isolated chick embryo retina model. Retina segments were incubated either with NMDA alone (100 μM) or with NMDA and TGB or VGB (10–1,000 μM, added 5 min before NMDA). Retina damage was assessed after 24 h by measuring lactate dehydrogenase (LDH) activity present in the medium and by histological analysis. Both drugs reduced LDH release in a dose-dependent manner with comparable mean maximal values of 56.6–63.7% achieved at concentration of 1 mM. Histological analysis of retina slices was in line with the biochemical assays and showed partial preservation of drug exposed retina structure with reduced edema especially in the inner plexiform layer. The present data provide pharmacological evidence that both TGB and VGB reduce the severity of NMDA-induced excitotoxic damage. Although an increase in GABAergic transmission might play a role, this in itself is insufficient to explain the neuroprotective effect of the two drugs and the exact mechanism remains to be elucidated.

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

Similar content being viewed by others

References

  • Abel MS, McCandless DW (1992) Elevated γ-aminobutyric acid levels attenuate the metabolic response to bilateral ischemia. J Neurochem 58:740–744

    Article  PubMed  CAS  Google Scholar 

  • Angehagen M, Ben-Menachem E, Ronnback L, Hansson E (2003) Novel mechanisms of action of three antiepileptic drugs, vigabatrin, tiagabine, and topiramate. Neurochem Res 28:333–340

    Article  PubMed  CAS  Google Scholar 

  • Bormann J (2000) The ‘ABC’ of GABA receptors. Trends Pharmacol Sci 21:16–19

    Article  PubMed  CAS  Google Scholar 

  • Calabresi P, Cupini LM, Centonze D, Pisani F, Bernardi G (2003) Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia. Ann Neurol 53:693–702

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Moulder K, Tenkova T, Hardy K, Olney JW, Romano C (1999) Excitotoxic cell death dependent on inhibitory receptor activation. Exp Neurol 160:215–225

    Article  PubMed  CAS  Google Scholar 

  • Colbourne F, Corbett D (1994) Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res 654:265–272

    Article  PubMed  CAS  Google Scholar 

  • Costa C, Leone G, Saulle E, Pisani F, Bernardi G, Calabresi P (2004) Coactivation of GABAA and GABAB receptor results in neuroprotection during in vitro ischemia. Stroke 35:596–600

    Article  PubMed  CAS  Google Scholar 

  • Dietrich WD, Busto R, Alonso O, Globus MYT, Ginsberg MD (1993) Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab 13:541–549

    PubMed  CAS  Google Scholar 

  • Doble A (1999) The role of excitotoxicity in neurodegenerative disease implications for therapy. Pharmacol Ther 81:163–221

    Article  PubMed  CAS  Google Scholar 

  • Duboc A, Hanoteau N, Simonutti M, Rudolf G, Nehlig A, Sahel JA, Picaud S (2004). Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats. Ann Neurol 55(5):695–705

    Article  PubMed  CAS  Google Scholar 

  • Ferraro L, Manganelli S, O’Connor WT, Francesconi W, Loche A, Gessa GL, Antonelli T (2001) gamma-Hydroxybutyrate modulation of glutamate levels in the hippocampus: an in vivo and in vitro study. J Neurochem 78:929–939

    Article  PubMed  CAS  Google Scholar 

  • Globus MY, Ginsberg MD, Busto R (1991) Excitotoxic index, a biochemical marker of selective vulnerability. Neurosci Lett 127:39–42

    Article  PubMed  CAS  Google Scholar 

  • Halonen T, Pitkanen A, Saano V, Riekkinen PJ (1991) Effects of vigabatrin (GVG) on the neurotransmission-related aminoacids and on GABA and benzodiazepine receptor binding in rats. Epilepsia 32:242–249

    Article  PubMed  CAS  Google Scholar 

  • Ientile R, Macaione V, Teletta M, Pedale S, Torre V, Macaione S (2001) Apoptosis and necrosis occurring in excitotoxic cell death in isolated chick. J Neurochem 79:71–78

    Article  PubMed  CAS  Google Scholar 

  • Inglefield JR, Perry JM, Scwartz RD (1995) Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus. Hippocampus 5:460–468

    Article  PubMed  CAS  Google Scholar 

  • Izumi Y, Ishikawa M, Benz AM, Izumi M, Zorumski CF, Thio LL (2004) Acute vigabatrin retinotoxicity in albino rats depends on light but not GABA. Epilepsia 45(9):1043–1048

    Article  PubMed  CAS  Google Scholar 

  • Krauss GL, Johnson MA, Shet S, Miller NR (2003) A controlled study comparing visual function in patients treated with vigabatrin and tiagabine. J Neurol Neurosurg Psychiatry 74:339–343

    Article  PubMed  CAS  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622

    Article  PubMed  CAS  Google Scholar 

  • Lukasiuk K, Pitkänen A (2000) GABAA-mediated toxicity of hippocampal neurons in vitro. J Neurochem 74:2445–2454

    Article  PubMed  CAS  Google Scholar 

  • Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 130:1007–1015

    Google Scholar 

  • Muir JK, Lobner D, Monyer H, Choi DW (1996) GABAA receptor activation attenuates excitotoxicity but exacerbates oxygen-glucose deprivation-induced neuronal injury in vitro. J Cereb Blood Flow Metab 16:1211–1218

    Article  PubMed  CAS  Google Scholar 

  • Pisani F, Pedale S, Macaone V, D’Angelo R, Oteri G, Macaione S, Ientile R (2001) Neuroprotective effects of lamotrigine and remacemide on excitotoxicity induced by glutamate agonists in isolated chick retina. Exp Neurol 170:162–170

    Article  PubMed  CAS  Google Scholar 

  • Romano C, Price MT, Olney JW (1995) Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina. J Neurochem 65:59–67

    Article  PubMed  CAS  Google Scholar 

  • Rosenbaum PS, Gupta H, Savitz SI, Rosenbaum DM (1997) Apoptosis in the retina. Clin Neurosci 4:224–232

    PubMed  CAS  Google Scholar 

  • Schwartz-Bloom RD, Sah R (2001) γ-Aminobutyric acidA neurotransmission and cerebral ischemia. J Neurochem 77:353–371

    Article  PubMed  CAS  Google Scholar 

  • Shen DW, Higgs MH, Salvay D, Olney JW, Lukasiewicz PD, Romano C (2002) Morphological and electrophysiological evidence for an ionotropic GABA receptor of novel pharmacology. J Neurophysiol 87:250–256

    PubMed  CAS  Google Scholar 

  • Shuaib A, Ijaz S, Hasan S, Kalra J (1992) Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulate damage in repetitive transient forebrain ischemia. Brain Res 590:13–17

    Article  PubMed  CAS  Google Scholar 

  • Sills GJ, Butler E, Forrest G, Ratnaraj N, Patsalos PN, Brodie MJ (2003) Vigabatrin, but not gabapentin or topiramate, produces concentration-related effects on enzymes and intermediates of the GABA shunt in rat brain and retina. Epilepsia 44(7):886–892

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was partially supported by a MURST grant.

Author information

Authors and Affiliations

  1. Department of Neurosciences, Psychiatric and Anesthesiological Sciences, First Neurological Clinic, University of Messina, Messina, Italy

    Francesco Pisani & Giancarla Oteri

  2. Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy

    Daniela Caccamo, Gaetano Gorgone & Riccardo Ientile

  3. Department of Biomorphology, University of Messina, Messina, Italy

    Emanuela Mazzon

  4. Neurology Clinic, University of Perugia, Perugia, Italy

    Cinzia Costa & Paolo Calabresi

  5. Clinica Neurologica 1a, Policlinico, via C Valeria, 98125 , Messina, Italy

    Francesco Pisani

Authors
  1. Francesco Pisani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cinzia Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Caccamo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Emanuela Mazzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gaetano Gorgone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giancarla Oteri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paolo Calabresi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Riccardo Ientile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesco Pisani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pisani, F., Costa, C., Caccamo, D. et al. Tiagabine and vigabatrin reduce the severity of NMDA-induced excitotoxicity in chick retina. Exp Brain Res 171, 511–515 (2006). https://doi.org/10.1007/s00221-005-0298-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-005-0298-1

Keywords

Search

Navigation