Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability

Oláh Gáspár, Judit Herédi, Ákos Menyhárt, Czinege Zsolt, Dávid Nagy, János Fuzik, Kitti Kocsis, Levente Knapp, Erika Krucsó, Levente Gellért, Z. Kis, T. Farkas, F. Fülöp, A. Párdutz, J. Tajti, L. Vécsei, J. Toldi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cortical spreading depression (CSD) involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation. The aim of this study was to investigate the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA) and dizocilpine, on CSD and the related blood-brain barrier (BBB) permeability in rats. In intact animals, KYNA hardly crosses the BBB but has some positive features as compared with its precursor L-Kynurenine, which is frequently used in animal studies (KYNA cannot be metabolized to excitotoxic agents such as 3-hydroxy-L-kynurenine and quinolinic acid). We therefore investigated the possible effects of peripherally administered KYNA. Repetitive CSD waves were elicited by the application of 1 M KCl solution to the cortex. Direct current-electrocorticograms were measured for 1 hour. Four parameters of the waves were compared. Evans blue dye and fuorescent microscopy were used to study the possible changes in the permeability of the BBB. The results demonstrated that N-methyl-D-aspartate receptor antagonists can reduce the number of CSD waves and decrease the permeability of the BBB during CSD. These results suggest that KYNA itself or its derivatives may offer a new approach in the therapy of migraines.

Original languageEnglish
Pages (from-to)981-987
Number of pages7
JournalDrug Design, Development and Therapy
Volume7
DOIs
Publication statusPublished - Sep 13 2013

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Cortical Spreading Depression
Kynurenic Acid
Blood-Brain Barrier
Permeability
Kynurenine
N-Methyl-D-Aspartate Receptors
Quinolinic Acid
Migraine with Aura
Evans Blue
Dizocilpine Maleate
Microcirculation
Migraine Disorders
Neuroglia
Glutamic Acid
Microscopy
Coloring Agents
Stroke
Neurons
Brain

Keywords

  • Blood-brain barrier
  • Cortical spreading depression
  • Glutamate receptors
  • Kynurenic acid
  • Kynurenines
  • NMDAR

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability. / Gáspár, Oláh; Herédi, Judit; Menyhárt, Ákos; Zsolt, Czinege; Nagy, Dávid; Fuzik, János; Kocsis, Kitti; Knapp, Levente; Krucsó, Erika; Gellért, Levente; Kis, Z.; Farkas, T.; Fülöp, F.; Párdutz, A.; Tajti, J.; Vécsei, L.; Toldi, J.

In: Drug Design, Development and Therapy, Vol. 7, 13.09.2013, p. 981-987.

Research output: Contribution to journalArticle

Gáspár, Oláh ; Herédi, Judit ; Menyhárt, Ákos ; Zsolt, Czinege ; Nagy, Dávid ; Fuzik, János ; Kocsis, Kitti ; Knapp, Levente ; Krucsó, Erika ; Gellért, Levente ; Kis, Z. ; Farkas, T. ; Fülöp, F. ; Párdutz, A. ; Tajti, J. ; Vécsei, L. ; Toldi, J. / Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability. In: Drug Design, Development and Therapy. 2013 ; Vol. 7. pp. 981-987.
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