2003 Fiscal Year Final Research Report Summary
Protection of neonatal brain against hypoxic-ischemic injury through regulating apoptosis.
| Project/Area Number |
14207043
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Naoki Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (20314487)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Tamaki Kobe University, Hospital, Lecturer, 医学部附属病院, 講師 (60362779)
TAKESHIMA Yasuhiro Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40281141)
TSUNEISHI Syuichi Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (10271040)
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| Project Period (FY) |
2002 – 2003
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| Keywords | hypoxic-ischemic encephalonathy / PDGF-α receptor / oligodendrocyte / apoptosis / differentiation / 低酸素性虚血性脳症 |
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| Research Abstract |
The aim of this study is to determine the roles of platelet-derived growth factor-a receptor (PDGF-Rα) activation against hypoxic-ischemic (HI) brain injury.
Hypoxic-ischemia (HI) causes injury to oligodendrocytes (OLs), cells which create the myelin sheath in the developing brain. OLs pass successively through progenitor and immature stages during differentiation into mature OLs. Only the OL progenitors express the platelet-derived growth factor-α receptor (PDGF-Rα), whose activation results in OL proliferation, but not OL differentiation. To study the response of OL progenitors and its role in protection after neonatal HI brain injury, we investigated the expression of PDGF-Rα in a neonatal rat stroke model (combination of left common carotid artery ligation and exposure to 8%O_2 for 2 h). We also compared PDGF-Rα expression with that of proteolipid protein (PLP) and myelin basic protein (MBP), which are representative markers of mature OLs. In the damaged cerebral cortex, PDGF-Rα mRNA levels increased significantly (p<0.01) with a peak at 0.5 h after HI insult, and returned to baseline levels within 168 h post-injury. Immunohistochemistry showed clear staining of PDGF-Rα only in the injured cerebral cortex at 72 h after HI insult. In contrast, no staining was observed in the cortex of sham-operated controls. At 168 h post-insult, immunopositive staining of PLP and MBP was found only in the damaged cortical areas where the PDGF-Rα immunopositive staining had been detected. These results indicate that the expression of PDGF-Rα increases rapidly and transiently only in the injured cerebral cortex after HI insult and may play a role in cellular repair or survival processes through the regulation of OL progenitor cell differentiation.
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