title: Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia.
abstract: Endogenous neural stem cells become "activated" after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3-7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made up the microenvironment to increase the neuronal plasticity of activated endogenous neural stem cells. Moreover, neural precursor cells after large-scale cortical injury could be recruited from the cortex nearby infarct core and subventricular zone.
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Na
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jeong-Kil
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School, Gwangju, Korea ; Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
keywords: brain ischemia; hypoxiainducible factor 1α; microenvironment; nerve regeneration; neural precursor cell; neural regeneration; neural stem cell; photothrombosis; vascular endothelial growth factor