Is Periventricular Leukomalacia an Axonopathy as Well as an Oligopathy?

Periventricular leukomalacia is a white matter disorder, the neonatal cranial ultrasound images of which predict long-term developmental limitations among preterm infants. The vulnerability of oligodendrocytes has led to the hypothesis that oligodendrocytes suffer the primary damage, with axonal damage occurring as a consequence. In this article, we discuss the differential role of oligodendrocytes and axons in this disorder's etiology, offering analogies from the multiple sclerosis and hydrocephalus literature. We conclude that it is too early to view periventricular leukomalacia exclusively as a consequence of oligodendrocyte damage and/or maldevelopment.

[1]  T. Möller,et al.  Rapid Ischemic Cell Death in Immature Oligodendrocytes: A Fatal Glutamate Release Feedback Loop , 2000, The Journal of Neuroscience.

[2]  M. Mizuguchi,et al.  Immunohistochemical expression of tumor necrosis factor α in neonatal leukomalacia , 1996 .

[3]  M. Cuénod,et al.  Murine brain macrophages induce NMDA receptor mediated neurotoxicity in vitro by secreting glutamate , 1991, Neuroscience Letters.

[4]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[5]  P. Gressens,et al.  Effect of ibotenate on brain development: an excitotoxic mouse model of microgyria and posthypoxic-like lesions. , 1995 .

[6]  R. Romero,et al.  Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1β, and tumor necrosis factor-α), neonatal brain white matter lesions, and cerebral palsy , 1997 .

[7]  D. Giulian,et al.  Phagocytic microglia release cytokines and cytotoxins that regulate the survival of astrocytes and neurons in culture , 1994, Neurochemistry International.

[8]  J. Pinto-Martin,et al.  Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. , 1995, Pediatrics.

[9]  M. R. Bigio,et al.  Cell Death, Axonal Damage, and Cell Birth in the Immature Rat Brain Following Induction of Hydrocephalus , 1998, Experimental Neurology.

[10]  F A Jolesz,et al.  Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques. , 1999, The Journal of pediatrics.

[11]  W. Brück,et al.  Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions , 1998, Multiple sclerosis.

[12]  F. Gilles,et al.  Are hypertrophic astrocytes a sufficient criterion of perinatal telencephalic leucoencephalopathy?1 , 1973, Journal of Neurology Neurosurgery & Psychiatry.

[13]  D. Arnold.  Magnetic resonance spectroscopy: imaging axonal damage in MS , 1999, Journal of Neuroimmunology.

[14]  P M Matthews,et al.  Imaging axonal damage of normal-appearing white matter in multiple sclerosis. , 1998, Brain : a journal of neurology.

[15]  F. Gilles,et al.  Perinatal telencephalic leucoencephalopathy. , 1969, Journal of neurology, neurosurgery, and psychiatry.

[16]  M Marín-Padilla,et al.  Developmental neuropathology and impact of perinatal brain damage. III: gray matter lesions of the neocortex. , 1997, Journal of neuropathology and experimental neurology.

[17]  J. Szaflarski,et al.  CYTOKINES AND PERINATAL BRAIN INJURY , 1997, Neurochemistry International.

[18]  J. Dambrosia,et al.  Neonatal cytokines and coagulation factors in children with cerebral palsy , 1998, Annals of neurology.

[19]  M. Mizuguchi,et al.  Expression of β-amyloid precursor protein in axons of periventricular leukomalacia brains , 1995 .

[20]  D. Graham,et al.  Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion , 1997, Brain Research.

[21]  N. Van Rooijen,et al.  Depletion of Systemic Macrophages by Liposome‐Encapsulated Clodronate Attenuates Increases in Brain Quinolinic Acid During CNS‐Localized and Systemic Immune Activation , 1999, Journal of neurochemistry.

[22]  J. Renauld,et al.  Proinflammatory cytokines and interleukin‐9 exacerbate excitotoxic lesions of the newborn murine neopallium , 2000, Annals of neurology.

[23]  L. Rosengren,et al.  Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis , 1998, Journal of neurology, neurosurgery, and psychiatry.

[24]  R. Romero,et al.  Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. , 1997, American journal of obstetrics and gynecology.

[25]  L. Turski,et al.  Autoimmune encephalomyelitis ameliorated by AMPA antagonists , 2000, Nature Medicine.

[26]  A. Windebank,et al.  Myelination determines the caliber of dorsal root ganglion neurons in culture , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  V. Perry,et al.  Axonal damage in acute multiple sclerosis lesions. , 1997, Brain : a journal of neurology.

[28]  D. Pitt,et al.  Glutamate excitotoxicity in a model of multiple sclerosis , 2000, Nature Medicine.

[29]  J. Chi,et al.  High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia. , 1997, American journal of obstetrics and gynecology.

[30]  S. Waxman,et al.  Restoration of Normal Conduction Properties in Demyelinated Spinal Cord Axons in the Adult Rat by Transplantation of Exogenous Schwann Cells , 1996, The Journal of Neuroscience.

[31]  M. Blennow,et al.  Enhanced Expression of Interleukin (IL)-1 and IL-6 Messenger RNA and Bioactive Protein after Hypoxia-Ischemia in Neonatal Rats , 1996, Pediatric Research.

[32]  F. Gilles,et al.  Morphologic Abnormalities in Human Infant Cerebral White Matter Related to Gestational and Postnatal Age , 1974, Pediatric Research.

[33]  M. Marín‐padilla.  Developmental Neuropathology and Impact of Perinatal Brain Damage. II: White Matter Lesions of the Neocortex , 1997, Journal of neuropathology and experimental neurology.

[34]  S G Waxman,et al.  Axon conduction and survival in CNS white matter during energy deprivation: a developmental study. , 1998, Journal of neurophysiology.

[35]  L. Jacobson,et al.  Large cups in normal-sized optic discs: a variant of optic nerve hypoplasia in children with periventricular leukomalacia. , 1997, Archives of ophthalmology.

[36]  S. Brady,et al.  Unwrapping new layers of complexity in axon/glial relationships , 2000, Glia.

[37]  R. Weller,et al.  Cerebral biopsy and assessment of brain damage in hydrocephalus. , 1975, Archives of disease in childhood.

[38]  P. Gressens,et al.  Intrauterine Infection Induces Programmed Cell Death in Rabbit Periventricular White Matter , 2000, Pediatric Research.

[39]  J. Dambrosia,et al.  Interferons and cerebral palsy. , 1999, The Journal of pediatrics.

[40]  K. Baba,et al.  Early axonal and glial pathology in fetal sheep brains with leukomalacia induced by repeated umbilical cord occlusion , 1999, Brain and Development.

[41]  T. O'Shea,et al.  Prenatal events and the risk of cerebral palsy in very low birth weight infants. , 1998, American journal of epidemiology.

[42]  Sachio Takashima,et al.  Early detection of axonal and neuronal lesions in prenatal-onset periventricular leukomalacia , 1997, Brain and Development.

[43]  A. Leviton,et al.  Characteristics of cranial ultrasound white‐matter echolucencies that predict disability: a review , 1999, Developmental medicine and child neurology.

[44]  C. Palmer.  Hypoxic-ischemic encephalopathy. Therapeutic approaches against microvascular injury, and role of neutrophils, PAF, and free radicals. , 1995, Clinics in perinatology.

[45]  O. Dammann,et al.  DEVELOPMENT OF A REGIONAL COHORT OF VERY‐LOW‐BIRTHWEIGHT CHILDREN AT SIX YEARS: COGNITIVE ABILITIES ARE ASSOCIATED WITH NEUROLOGICAL DISABILITY AND SOCIAL BACKGROUND , 1996, Developmental medicine and child neurology.

[46]  Scott T. Brady,et al.  Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells , 1992, Cell.

[47]  M. Schachner,et al.  Crucial Role for the Myelin‐associated Glycoprotein in the Maintenance of Axon‐Myelin Integrity , 1995, The European journal of neuroscience.

[48]  M. Mizuguchi,et al.  Immunohistochemical expression of tumor necrosis factor alpha in neonatal leukomalacia. , 1996, Pediatric neurology.

[49]  A Benazzouz,et al.  Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization transfer. , 1995, AJNR. American journal of neuroradiology.

[50]  W. Brück,et al.  Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. , 2000, Brain : a journal of neurology.

[51]  K. Blomgren,et al.  Chemokine and Inflammatory Cell Response to Hypoxia-Ischemia in Immature Rats , 1999, Pediatric Research.

[52]  B. Banker,et al.  Periventricular leukomalacia of infancy. A form of neonatal anoxic encephalopathy. , 1962, Archives of neurology.

[53]  L. Horrocks,et al.  Aluminum silicate toxicity in cell cultures , 1993, Neuroscience.

[54]  J. Drake,et al.  Acute and Chronic Cerebral White Matter Damage in Neonatal Hydrocephalus , 1994, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[55]  Virginia M. Y. Lee,et al.  Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton , 1999, The Journal of Neuroscience.

[56]  J. Kimura,et al.  Tumor necrosis factor-alpha in peripheral nerve lesions. , 1998, Acta neuropathologica.

[57]  R. Nixon,et al.  Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation , 1996, The Journal of Neuroscience.

[58]  出口貴美子.  Characteristic Neuropathology of Leukomalacia in Extremely Low Birth Weight Infants(超低出生体重児の白質軟化の神経病理学的特徴) , 1997 .

[59]  B. Trapp,et al.  The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes , 1989, The Journal of cell biology.

[60]  C. Truwit,et al.  Cerebral palsy: MR findings in 40 patients. , 1992, AJNR. American journal of neuroradiology.

[61]  M. D. Del Bigio,et al.  Myelination Delay in the Cerebral White Matter of Immature Rats with Kaolin‐induced Hydrocephalus Is Reversible , 1997, Journal of neuropathology and experimental neurology.

[62]  J. Chi,et al.  Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits. , 1997, American journal of obstetrics and gynecology.

[63]  H. Kinney,et al.  Human oligodendroglial development: relationship to periventricular leukomalacia. , 1998, Seminars in pediatric neurology.

[64]  K. Fischbeck,et al.  Is CMTX an axonopathy? , 1999, Neurology.

[65]  H. Kettenmann,et al.  Oligodendrocytes and Microglia Are Selectively Vulnerable to Combined Hypoxia and Hypoglycemia Injury in Vitro , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[66]  J. Chi,et al.  High expression of tumor necrosis factor-α and interleukin-6 in periventricular leukomalacia ☆ ☆☆ ★ ★★ ♢ , 1997 .

[67]  Ann-Mari Brubakk,et al.  Cerebral MRI of very low birth weight children at 6 years of age compared with the findings at 1 year , 1998, Pediatric Radiology.

[68]  J. Kimura,et al.  Tumor necrosis factor-α in peripheral nerve lesions , 1997, Acta Neuropathologica.

[69]  S. Back,et al.  Cellular and molecular pathogenesis of periventricular white matter injury , 1997 .

[70]  R. Kikinis,et al.  Periventricular white matter injury in the premature infant is followed by reduced cerebral cortical gray matter volume at term , 1999, Annals of neurology.

[71]  M. Sendtner,et al.  Does oligodendrocyte survival depend on axons? , 1993, Current Biology.

[72]  M. Schwab,et al.  Degeneration and regeneration of axons in the lesioned spinal cord. , 1996, Physiological reviews.

[73]  P. Matthews,et al.  Putting Magnetic Resonance Spectroscopy Studies in Context: Axonal Damage and Disability in Multiple Sclerosis , 1998, Seminars in neurology.