Bilateral intranigral NMDA blockade increases status duration and neuronal injury from systemic kainic acid.
Limbic seizures may be under the regulation of the substantia nigra, pars reticulata (SNpr). Using microinjection of the NMDA antagonist AP7, we investigated the role of SNpr in modulating seizures induced by kainic acid. Seizure severity was analyzed electrographically and neural injury assessed by measurement of heat shock protein (HSP) expression and acid fuchsin (AF) staining of vulnerable hippocampal cells. Intranigral injection of AP-7 increased the duration of electrographic seizure discharges and the number of HSP-positive and acid fuchsin stained cells in all hippocampal sectors, suggesting that blockade of the NMDA receptors in SNpr enhanced neural injury.
Tanaka
K
K
University of California, San Francisco.
Lowry
T
T
Simon
R P
RP
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D003975:Diazepam / Q000494:pharmacology; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects; D007839:Functional Laterality; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007608:Kainic Acid / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000596:Amino Acids; D000927:Anticonvulsants; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002245:Carbon Dioxide; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid; D003975:Diazepam; D010100:Oxygen; D007608:Kainic Acid