Upregulation of vascular endothelial growth factor receptors Flt-1 and Flk-1 in rat hippocampus after transient forebrain ischemia.
This study characterizes the distribution of the two tyrosine kinase receptors for vascular endothelial growth factor (VEGF), Flt-1 and Flk-1, in the rat hippocampus following transient forebrain ischemia. The semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of Flt-1 and Flk-1 in hippocampal CA1 showed upregulation of these receptors following ischemic injury. Expression of Flt-1 and Flk-1 mRNA was restricted to neurons in the pyramidal cell and granule cell layers in control animals; however, upregulation was detected in activated glial cells and in the vascular endothelial cells rather than in neurons, in ischemic hippocampi. Most of the activated glial cells expressing Flt-1 and Flk-1 were reactive astrocytes, although some were microglial cells. The spatiotemporal expression of Flt-1 in the ischemic hippocampus mirrored that of Flk-1 expression. Expression of mRNA for both receptors was induced after 12 h, appeared to be increased progressively until 3 days when the highest expression was reached, and was sustained for more than 2 weeks. Flt-1 and Flk-1 immunoreactivity in the ischemic hippocampus matched the mRNA induction patterns except for a somewhat delayed onset. These data suggest that VEGF may be involved in the glial response via specific VEGF receptors in the rat hippocampus following transient forebrain ischemia.
Choi
Jeong-Sun
JS
Department of Anatomy, College of Medicine, Catholic University of Korea, Seoul, Korea.
Kim
Ha-Young
HY
Cha
Jung-Ho
JH
Choi
Jae-Youn
JY
Chun
Myung-Hoon
MH
Lee
Mun-Yong
MY
D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2