title: Myelin abnormalities without oligodendrocyte loss in periventricular leukomalacia.
abstract: The cellular basis of myelin deficits detected by neuroimaging in long-term survivors of periventricular leukomalacia (PVL) is poorly understood. We tested the hypothesis that oligodendrocyte lineage (OL) cell density is reduced in PVL, thereby contributing to subsequent myelin deficits. Using computer-based methods, we determined OL cell density in sections from 18 PVL and 18 age-adjusted control cases, immunostained with the OL-lineage marker Olig2. Myelination was assessed with myelin basic protein (MBP) immunostaining. We found no significant difference between PVL and control cases in Olig2 cell density in the periventricular or intragyral white matter. We did find, however, a significant increase in Olig2 cell density at the necrotic foci, compared with distant areas. Although no significant difference was found in the degree of MBP immunostaining, we observed qualitative abnormalities of MBP immunostaining in both the diffuse and necrotic components of PVL. Abnormal MBP immunostaining in PVL despite preserved Olig2 cell density may be secondary to arrested OL maturation, damage to OL processes, and/or impaired axonal-OL signaling. OL migration toward the "core" of injury may occur to replenish OL cell number. This study provides new insight into the cellular basis of the myelin deficits observed in survivors of PVL.
authors.affiliation: Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Saraid S
authors.initials: SS
authors.lastname: Billiards
authors.forename: Robin L
authors.initials: RL
authors.lastname: Haynes
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Folkerth
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Borenstein
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Trachtenberg
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Volpe
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
mesh_terms: D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000378:metabolism; D007969:Leukomalacia, Periventricular / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D037121:Plant Lectins / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D037121:Plant Lectins; D014746:Vimentin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C489788:MAP2 protein, human; C405708:OLIG2 protein, human; C034981:tomato lectin