title: Juvenile striatal white matter is resistant to ischemia-induced damage.
abstract: White matter injury following ischemic stroke is a major cause of functional disability. Injury to both myelinated axons and oligodendrocytes, the myelin producing cells in the central nervous system, occurs in experimental models of ischemic stroke. Age-related changes in white matter vulnerability to ischemia have been extensively studied and suggest that both the perinatal and the aged periods are times of increased white matter vulnerability. However, sensitivity of white matter following stroke in the juvenile brain has not been evaluated. Interestingly, the late pediatric period is an important developmental stage, as it is the time of maximal myelination. The current study demonstrates that neurons in late pediatric/juvenile striatum are vulnerable to ischemic damage, with neuronal injury being comparable in juvenile and adult mice following ischemia. By contrast, actively myelinating striatal oligodendrocytes in the juvenile brain are resistant to ischemia, whereas adult oligodendrocytes are quite sensitive. As a result, myelin sheaths are remarkably intact and axons survive well in the injured striatum of juvenile mice. In addition to relative resistance of juvenile white matter, other glial responses were very different in juvenile and adult mice following cerebral ischemia, including differences in astrogliosis, fibrosis, NG2-cell reactivity, and vascular integrity. Together, these responses lead to long-term preservation of brain parenchyma in juvenile mice, compared to severe tissue loss and scarring in adult mice. Overall, the current study suggests that equivalent ischemic insults may result in less functional deficit in children compared to adults and an environment more conducive to long-term recovery. GLIA 2016;64:1972-1986.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.|Neuroscience Graduate Program, University of Colorado School of Medicine, Aurora, Colorado.|Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Jared T
authors.initials: JT
authors.lastname: Ahrendsen
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Himmat S
authors.initials: HS
authors.lastname: Grewal
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Hickey
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Culp
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.|Neuroscience Graduate Program, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gould
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Takeru
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Strnad
authors.affiliation: Neuroscience Graduate Program, University of Colorado School of Medicine, Aurora, Colorado.|Deparment of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Traystman
authors.affiliation: Neuroscience Graduate Program, University of Colorado School of Medicine, Aurora, Colorado.|Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Paco S
authors.initials: PS
authors.lastname: Herson
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado. wendy.macklin@ucdenver.edu.|Neuroscience Graduate Program, University of Colorado School of Medicine, Aurora, Colorado. wendy.macklin@ucdenver.edu.|Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, Colorado. wendy.macklin@ucdenver.edu.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D020520:Brain Infarction / Q000209:etiology; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D056784:Leukoencephalopathies / Q000209:etiology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009185:Myelin Proteins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; C495678:Slc2a1 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D005982:Glutathione Transferase
keywords: astrocyte; gliosis; myelin; oligodendrocyte; stroke; vasculature