MK-801 inhibits the cortical increase in IGF-1, IGFBP-2 and IGFBP-4 expression following trauma.
Cerebral contusions increase cortical expression of insulin-like growth factor 1 (IGF-1), IGF binding protein-2 (IGFBP-2) and IGFBP-4, mRNA levels increase at the contusion site (IGF-1, IGFBP-2 and -4) and along the ipsilateral cortex (IGFBP-2 and -4). Here we explore whether this upregulation is glutamate dependent. Rats were treated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or the non-NMDA antagonist CNQX before and after trauma, and analysed using quantitative in situ hybridization. The induction of IGF-1 expression was completely blocked by MK-801 or CNQX. IGFBP-2 mRNA levels remained high at the contusion site in the presence of either drug, but the increase was blocked in the cortex temporal to the impact by MK-801. The increase in IGFBP-4 mRNA was blocked by MK-801 but not by CNQX.
Nordqvist
A C
AC
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Holmin
S
S
Nilsson
M
M
Mathiesen
T
T
Schalling
M
M
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000187:drug effects* / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D007334:Insulin-Like Growth Factor I; D016291:Dizocilpine Maleate