Vascular endothelial growth factor gene expression in middle cerebral artery occlusion in the rat.
BACKGROUND
Focal cerebral ischemia induces up-regulation of angiogenic growth factors such as vascular endothelial growth factor (VEGF), which may have both beneficial and harmful effects to the ischemic brain. Vascular endothelial growth factor is up-regulated in models of brain ischemia, but the underlying mechanisms in vivo remain unclear. In the present report we have investigated the concomitant changes in VEGF and glyceraldehyde dehydrogenase (GAPDH) mRNA expression in a model of permanent and transient cerebral ischemia.


METHODS
Male Sprague-Dawley rats were exposed to permanent or transient (2 h) middle cerebral artery occlusion (PMCAO, TMCAO). Brain samples were collected at survival times ranging from 6 h to 1 week, and the levels of VEGF164 and GAPDH mRNA were determined using reverse-transcriptase real-time polymerase chain reaction (RT-PCR).


RESULTS
The VEGF mRNA levels decreased gradually over the observation period in a similar manner in both PMCAO and TMCAO. Maximum levels, seen at early observation time points, did not significantly deviate from sham controls. No statistically significant changes in GAPDH mRNA levels were observed, but there was a tendency towards a postischemic decrease with subsequent return to control levels over time. The VEGF/GAPDH ratio followed a pattern of decrease similar to VEGF mRNA alone.


CONCLUSIONS
The VEGF mRNA levels at 6 h after MCAO remain near baseline and thereafter decline, regardless of whether the occlusion is permanent or transient (2 h). The findings raise the question of other than transcriptional regulation of VEGF in cerebral ischemia.
Lennmyr
F
F
Department of Surgical Sciences, Section of Anesthesiology and Intensive Care, University Hospital, Uppsala University, Uppsala, Sweden. Fredrik.Lennmyr@surgsci.uu.se
Terént
A
A
Syvänen
A-C
AC
Barbany
G
G
D000818:Animals; D001923:Brain Chemistry; D004587:Electrophoresis, Agar Gel; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases