Project/Area Number |
14370434
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
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Research Institution | OKAYAMA UNIVERSITY |
Principal Investigator |
NINOMIYA Yoshifumi Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Professor, 大学院・医歯学総合研究科, 教授 (70126241)
|
Co-Investigator(Kenkyū-buntansha) |
HIROHATA Satoshi Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Assistant Professor, 大学院・医歯学総合研究科, 助手 (90332791)
OOHASHI Toshitaka Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Instructor, 大学院・医歯学総合研究科, 講師 (50194262)
YONEZAWA Tomoko Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Mol. Biol. & Biochem., Assistant Professor, 大学院・医歯学総合研究科, 助手 (30304299)
OHTSUKA Aiji Okayama Univ., Grad. Sch. of Med. & Dent., Dept. of Human Morphology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (50168986)
|
Project Period (FY) |
2002 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥9,900,000 (Direct Cost: ¥9,900,000)
|
Keywords | basement membrane / capillary / endothelial cell / type IV collagen / astrocyte |
Research Abstract |
We report the molecular cloning of a new member of the transmembrane-type immunoglobulin superfamily and designate the encoded protein as limitrin since it selectively localized to glia limitans in mouse brain. Limitrin cDNA was obtained using a subtractive hybridization procedure designed to identify molecules responsible for blood-brain barrier function. Western blots using a limitrin-specific antibody demonstrated that the gene product is expressed significantly in mouse brain and primary murine astrocytes, and is distributed in the plasma membrane. Immunohistochemical studies using confocal and electron microscopy clearly demonstrated highly polarized localization in astroglial endfeet in the perivascular region and under the pia mater in vivo. Limitrin is expressed in spinal cord and many areas of the brain but not in the median eminence or subfornical organ (the circumventricular organs) where the blood-brain barrier is lacking. Disruption of the blood-brain barrier by cold injury resulted in a drastic reduction in limitrin expression. Furthermore, during retrieval from cold injury the increased expression of limitrin in perivascular endfeet correlated with the recovery of angiogenesis in capillaries within the lesion margins. Our results suggest that limitrin is physically and functionally associated with the blood-brain barrier, implying that this protein may be useful as a diagnostic determinant of barrier integrity.
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