title: After Intracerebral Hemorrhage, Oligodendrocyte Precursors Proliferate and Differentiate Inside White-Matter Tracts in the Rat Striatum.
abstract: Damage to myelinated axons contributes to neurological deficits after acute CNS injury, including ischemic and hemorrhagic stroke. Potential treatments to promote re-myelination will require fully differentiated oligodendrocytes, but almost nothing is known about their fate following intracerebral hemorrhage (ICH). Using a rat model of ICH in the striatum, we quantified survival, proliferation, and differentiation of oligodendrocyte precursor cells (OPCs) (at 1, 3, 7, 14, and 28 days) in the peri-hematoma region, surrounding striatum, and contralateral striatum. In the peri-hematoma, the density of Olig2(+) cells increased dramatically over the first 7 days, and this coincided with disorganization and fragmentation of myelinated axon bundles. Very little proliferation (Ki67(+)) of Olig2(+) cells was seen in the anterior subventricular zone from 1 to 28 days. However, by 3 days, many were proliferating in the peri-hematoma region, suggesting that local proliferation expands their population. By 14 days, the density of Olig2(+) cells declined in the peri-hematoma region, and, by 28 days, it reached the low level seen in the contralateral striatum. At these later times, many surviving axons were aligned into white-matter bundles, which appeared less swollen or fragmented. Oligodendrocyte cell maturation was prevalent over the 28-day period. Densities of immature OPCs (NG2(+)Olig2(+)) and mature (CC-1(+)Olig2(+)) oligodendrocytes in the peri-hematoma increased dramatically over the first week. Regardless of the maturation state, they increased preferentially inside the white-matter bundles. These results provide evidence that endogenous oligodendrocyte precursors proliferate and differentiate in the peri-hematoma region and have the potential to re-myelinate axon tracts after hemorrhagic stroke.
authors.affiliation: Krembil Research Institute, University Health Network, Krembil Discovery Tower, Room 7KD-417, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Michael J E
authors.initials: MJ
authors.lastname: Joseph
authors.affiliation: Krembil Research Institute, University Health Network, Krembil Discovery Tower, Room 7KD-417, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada.
authors.forename: Jayalakshmi
authors.initials: J
authors.lastname: Caliaperumal
authors.affiliation: Krembil Research Institute, University Health Network, Krembil Discovery Tower, Room 7KD-417, 60 Leonard Street, Toronto, ON, M5T 2S8, Canada. schlicht@uhnres.utoronto.ca.|Department of Physiology, University of Toronto, Toronto, ON, Canada. schlicht@uhnres.utoronto.ca.
authors.forename: Lyanne C
authors.initials: LC
authors.lastname: Schlichter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002543:Cerebral Hemorrhage / Q000473:pathology* / Q000503:physiopathology*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D066127:White Matter / Q000473:pathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D011508:Chondroitin Sulfate Proteoglycans; D019394:Ki-67 Antigen; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C522729:Olig2 protein, rat
keywords: Corticostriatal axons; Hemorrhagic stroke; Myelinated axon tracts; Oligodendrocyte maturation; Peri-hematoma recovery; Post-stroke recovery