Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model.
Stroke is a devastating condition occurring in at least 1 in 4000 live births in the neonatal period. Since hypoxia-inducible factor (HIF)-1alpha can modulate ischemic injury via induction of target genes that may protect cells against ischemia, and is induced after preconditioning by hypoxia in the neonatal rat brain hypoxia-ischemia model, we evaluated whether HIF-1alpha is induced after focal ischemia-reperfusion, a model for neonatal stroke. We developed an ischemia-reperfusion model in postnatal day 10 (P10) rats by transiently occluding the middle cerebral artery (MCA) for 1.5 h. The MCA territory was reperfused for 0, 4, 8, or 24 h and the expression of HIF-1alpha and its target gene, vascular endothelial growth factor (VEGF), were delineated. HIF-1alpha protein and VEGF protein peaked at 8 h, and declined subsequently at 24 h in injured cortex following 1.5 h of MCA occlusion. Double-immunolabeling indicated that both HIF-1alpha and VEGF are expressed together in neurons with a similar time course of expression. The presence of HIF-1alpha and VEGF after moderate ischemia-reperfusion injury suggests potential avenues to exploit for neuroprotection.
Mu
Dezhi
D
Department of Neurology, University of California San Francisco, San Francisco, CA 94143, USA.
Jiang
Xiangning
X
Sheldon
R Ann
RA
Fox
Christine K
CK
Hamrick
Shannon E G
SE
Vexler
Zinaida S
ZS
Ferriero
Donna M
DM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D020521:Stroke / Q000378:metabolism* / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A