title: Pharmacological manipulation of the NMDA receptor differentially protects from systemic kainic acid neuropathology: evaluation through ornithine decarboxylase induction, morphology and GFAP immunohistochemistry.
abstract: The excitotoxic brain damage caused by systemic administration of kainic acid requires the activation of N-methyl-D-aspartate (NMDA) receptors in order to fully express its neurotoxic potency. We have tested the relative efficacy of different manipulations of the NMDA receptor on morphological, immunohistochemical and neurochemical parameters in this experimental model. A competitive (CGP 39551) and a non-competitive (MK 801) antagonist of the NMDA receptor, granted full protection against neuronal degeneration and consequent glial proliferation in the hippocampus and olfactory cortex, two regions severely affected by systemic administration of kainic acid. In addition, CGP 39551 completely counteracted the dramatic induction of the enzyme ornithine decarboxylase which occurs shortly after kainic acid administration. Systemic administration of high amounts of MgSO4 concomitantly and after kainic acid injection, appeared to partially prevent neuronal degeneration but had no clear effects on glial reaction and ornithine decarboxylase induction. Finally administration of an antagonist of the polyamine site present in the NMDA receptor (SL 82.0715), did not appear to have any protective effect at the dose used here. The present results help to better understand the ways by which it could be possible to counteract excitotoxic brain injuries.
authors.affiliation: Department of Biology, University of Bologna (Italy).
authors.forename: T
authors.initials: T
authors.lastname: Guarnieri
authors.forename: M
authors.initials: M
authors.lastname: Virgili
authors.forename: L
authors.initials: L
authors.lastname: Villani
authors.forename: F
authors.initials: F
authors.lastname: Facchinetti
authors.forename: A
authors.initials: A
authors.lastname: Contestabile
authors.forename: P
authors.initials: P
authors.lastname: Migani