Partial protection of hippocampal neurons by MK-801 during perforant path stimulation in the immature brain.
We investigated whether the non-competitive NMDA receptor antagonist, MK-801, could protect neurons in the immature brain from the excitotoxic affects of perforant path stimulation. A high dose of MK-801 reduced the number of injured hilar interneurons in the stimulated hippocampus from 30.0 +/- 5.2 in unmedicated rats to 12.2 +/- 9.6 in MK-801 treated animals (P < 0.05). MK-801 injection also protected the animals from the scattered dentate granule cell injury observed in non-medicated animals 1 day after stimulation. Other effects of drug injection included exacerbated damage in limbic cortices, retrosplenial cortical damage, and reduced inhibition in a highly epileptogenic region of the dentate gyrus. Our results show that a subpopulation of hilar interneurons is vulnerable to NMDA-induced damage in the immature hippocampus but that non-competitive blockade of the NMDA receptor may be a dangerous therapeutic strategy.
Thompson
K
K
University of California, Los Angeles, Department of Physiological Science 90095-1527, USA.
Wasterlain
C
C
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology
D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate