Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-D-aspartate receptor antagonist MK-801.
FOS and JUN proteins are transcription factors thought to be involved in coupling neuronal excitation to target gene expression. Cortical infarction of consistent size and location was produced by irradiating the rat brain with Xenon light through the intact skull for 20 min following systemic injection of the photo-sensitizing dye, rose bengal. To investigate the time course and distribution pattern of five cellular immediate early gene (IEG)-encoded proteins after focal ischemia, the expression of c-FOS, FOS B, c-JUN, JUN B and JUN D was studied immunocytochemically in sham-operated control animals and at different postischemic time intervals up to 24 h. A separate group of animals was pretreated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801. Photochemically induced focal ischemia caused a rapid induction of FOS and JUN proteins in the entire ipsilateral cortex apart from the ischemic focus. Immunoreactivity in the ipsilateral subcortical gray and white matter and in the entire contralateral hemisphere was indistinguishable from control animals. Individual IEG-encoded proteins were sequentially induced with increased levels of immunoreactivity persisting for different time periods up to 24 h. c-FOS, FOS B, c-JUN and JUN B exhibited a characteristic distribution pattern as reflected by different staining intensities in individual cortical layers. The rapid IEG induction in the entire ipsilateral sensorimotor and limbic structure-associated cortices after photochemically induced infarction most likely reflects spreading depression caused by ischemia and mediated by NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Gass
P
P
Department of Neuropathology, University of Heidelberg, Federal Republic of Germany.
Spranger
M
M
Herdegen
T
T
Bravo
R
R
Köck
P
P
Hacke
W
W
Kiessling
M
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D010777:Photochemistry; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate