title: Delayed neuronal injury induced by sub-lethal NMDA exposure in the hippocampal slice.
abstract: Stroke produces neuronal death by two general processes which differ in their temporal course. Acute neuronal death occurs within minutes, while delayed neuronal death evolves within 24 h. To better examine mechanisms of delayed death, we developed a new in vitro model of delayed neuronal injury using extended electrophysiological recordings in paired hippocampal slices. We exposed one hippocampal slice of each pair to 10 microM N-methyl-D-aspartate (NMDA) until the orthodromic CA1 PS disappeared. Thereafter, NMDA-treated slices regained near full recovery of PS amplitude within one hour. However, 10 h later, NMDA-treated slices demonstrated a rapid decline in PS amplitude of 82% +/- 15. CA1 orthodromic evoked PS was lost completely at an average 12.4 +/- 1.6 h after NMDA exposure. This sudden loss of response contrasted with paired, untreated slices, where CA1 PS could be elicited for 22.6 +/- 4.0 h (P < 0.05). Treatment with 10 mM MgCl2 begun after NMDA exposure and continued for 35 min, prevented delayed loss of CA1 orthodromic PS, which then could be elicited for 20.3 +/- 2.1 h. These results indicate that delayed injury can be evaluated using the hippocampal slice. They also suggest that activation of NMDA receptors can induce delayed neuronal injury in CA1 neurons, and that magnesium treatment after NMDA can prevent this injury.
authors.affiliation: Sepulveda VAMC, CA 91343, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Wallis
authors.forename: K L
authors.initials: KL
authors.lastname: Panizzon
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D016202:N-Methylaspartate; D008274:Magnesium