17-06-08(5:19:20)
Authors:
Liu DD 1,2
Chiang ES 3
Lin SZ 2
Shyu WC 2
Li H 4
Institutions:
1Department of Dentistry,China Medical University Hospital,Taichung,Taiwan
2Center of Neuropsychiatry,China Medical University Hospital,Taichung, Taiwan
3Graduate Institute of Oral Biology, National Yang Ming University,Taipei, Taiwan
4Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
Title of abstract : Upregulation of SDF-1/CXCR4 promotes neuroplasticity through enhancing PrPC-mediated neuritogenesis in hOEC/ONF-implanted stroke model
Abstract text:
Murine olfactory ensheathing cells (OECs) have been proven experimentally to promote central nervous system axonal regeneration in spinal cord injury models. We investigated whether OECs could induce a neuroplastic effect to improve the neurological dysfunction caused by hypoxic/ischemic stress. In this study, human OECs/olfactory nerve fibroblasts (hOECs/ONFs) specifically secreted trophic factors including stromal cell derived factor (SDF-1α). Rats with intracerebral hOEC/ONF implantation showed much more improvement in neurological deficit following stroke than control rats. [18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) showed increased glucose metabolic activity in the hOEC/ONF-treated group. Transplanted hOECs/ONFs and endogenous homing stem cells co-localized with specific neural and vascular markers (stem cell fusion), and both enhanced neuroplasticity in the ischemic brain. Upregulation of SDF-1α and CXC chemokine receptor 4 (CXCR4) in hOECs/ONFs promoted neurite outgrowth of cocultured primary cortical neurons under oxygen glucose deprivation (OGD) conditions and in stroke animals through upregulation of cellular prion protein (PrPC) expression. Therefore, the upregulation of SDF-1α, and enhancement of CXCR4 and PrPC interaction effected by hOEC/ONF implantation mediated neuroplastic signals in response to hypoxic and ischemic microenvironments.
