Time window and pharmacological characterisation of kainate-mediated preconditioning in organotypic rat hippocampal slice cultures.
Tolerance to normally neurotoxic insults can be induced by prior a preconditioning exposure to a sublethal insult. Kainate toxicity can be attenuated by prior exposure to very low concentrations of kainate both in vivo and in vitro. Using organotypic hippocampal slice cultures from rats we have shown that 5 microM kainate induces a selective lesion in the CA3 region and this can be significantly attenuated by 1 microM kainate administered 1-5 days earlier. The time window for this effect was affected by the length of time in culture, and preconditioning was blocked by NBQX but not the selective AMPA receptor antagonist GYKI53655. These data demonstrate a role for kainate receptors in preconditioning for the first time and show that organotypic cultures can be used as a model to investigate long-term preconditioning mechanisms.
Nvue
Rose
R
Clinical Neurosciences, Centre for Neurosciences, University of Southampton, Rm6207, Biomedical Sciences Building, Bassett Crescent East, SO16 7PX, UK.
Gorianov
Vitaly
V
Best
Nick
N
Sundstrom
Lars E
LE
Pringle
Ashley K
AK
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000139:chemically induced / Q000517:prevention & control; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects*; D007608:Kainic Acid / Q000378:metabolism / Q000633:toxicity*; D009924:Organ Culture Techniques; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D007608:Kainic Acid