뇌경색 백서모델에서 내재성 줄기세포의 활성에 미치는 HIF-1α 와 VEGF의 역할 = (The)Role of HIF-1α and VEGF expression for Endogenous Neural Stem Cell Activation in Photothrombotic Rat Stroke Model

다국어 초록 (Multilingual Abstract)

Background: Endogenous neural stem cells (NSCs) become “activated” after neuronal injury, but the activation mechanisms of endogenous NSCs are little known.
Methods: The present study evaluated the relationships between endogenous neural stem cell and HIF-1α and VEGF expression in a photothromobotic rat stroke model using immunohistochemistry and Western blotting. The present study also evaluated the chronological changes of endogenous neural stem cell by BrdU incorporation and compared with HIF-1α, VEGF expression in this model.
Results: The mRNA and protein expression of HIF-1α, VEGF, and nestin showed sequential changes after ischemic stroke. In Western blot analysis, HIF-1α was initially increased at 1 h, and VEGF was increased following HIF-1α. HIF-1α induction was observed at 1 h, and maximally increased at 12 h in the ipsilateral hemisphere. HIF-1α immunoreactivity was detected in the ipsilateral cortical neurons in the infarct core and peri-infarct area. VEGF positive immunostaining was identified in both cortex, but ipsilateral cortex staining intensity and numbers were higher compared to the contralateral cortex. VEGF positive neurons are easily found along the peri-infarct areas 12 h after ischemia. The expression of nestin increased throughout the microvasculature in both the ischemic core and the boundary zone in all experimental rats after 12 h of ischemic injury. Nestin immunoreactivity increased in SVZ during 12 h to day 3, and markedly increased in ipsilateral cortex between day 3 to 7. Nestin labeled cells showed dual differentiation with microvessels near the infarct core and astrocytes in areas outside of the microvessel-differentiated area. BrdU incorporated cells were gradually increased at day 1 in SVZ and ipsilateral cortex, followed by the observation of numerous BrdU-labeled cells were in peri-infarct and unlesionsed cortex at day 3. These BrdU-labeled cells were mainly co-labeled with nestin, GFAP and laminin, but not neuron.
Conclusions: Early expressions of HIF-1α and VEGF after ischemia make up the microenvironment to increase the neuronal plasticity of activated endogenous NSCs. Moreover, neural precursor cells after large cortical injury might be recruited from cortex nearby lesion and SVZ.

목차 (Table of Contents)

• Abstract 1
• Introduction 3
• Materials and methods 7
• Results 13
• Discussion 17
• References 22
• Abstract in Korean 31