Abstract 14
Category: Basic Science
At the end of the session, participants will be able to:
- To learn how the expression of keratan sulfate proteoglycan differs in the cerebellar system from supratentorial grey matter structures;
- To observe differences of KS expression in white matter fascicles in forebrain and in the posterior fossa;
- To know the biochemical nature of keratan sulfate proteoglycan and cells that synthesize and secrete it in the CNS.
COI Disclosure:
None to disclose.
Harvey B. Sarnat, MS, MD, FRCPC 1, Weiming Yu, MD, FRCPC 2, Laura Flores-Sarnat, MD 3
- Departments of Paediatrics, Pathology (Neuropathology), Clinical Neurosciences, University of Calgary and Alberta Children’s Hospital Research Institute (Owerko Centre), Calgary, Alberta, Canada
- Department of Pathology (Paediatric Anatomical Pathology), University of Calgary and Alberta Children’s Hospital, Calgary, Alberta, Canada
- Departments of Paediatrics, Clinical Neurosciences, University of Calgary and Alberta Children’s Hospital Research Institute (Owerko Centre), Calgary, Alberta, Canada
Presenter
Dr. Sarnat is Professor of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences at the University of Calgary (Canada), where he has practiced since 1981 He is board-certified in Paediatrics and in Neurology in the U.S. and in Neurology by the Royal College of Physicians and Surgeons of Canada. He is a graduate of the University of Illinois School of Medicine (Chicago) where he also received an M.S. degree in neuroanatomy. Residency training in child neurology and neuropathology at the University of Virginia (Charlottesville).
His academic interests and most research publications over many years are in the fields of neuroembryology, developmental (fetal and neonatal) neuropathology, brain malformation and the neuropathology of childhood epilepsy. He serves on Editorial Boards of 9 journals and has 220 research publications, has authored12 textbooks, and has contributed chapters to 130 specialty monographs. He is a member of the Commission on Neuropathology of the International League Against Epilepsy.
Dr. Sarnat has mentored numerous residents from several countries.
Distinguished awards include giving the keynote Gordon Mathieson Lecture at the 50th meeting of the Canadian Association of Neuropathologists in 2010 and again in 2021, the Bernard Sachs Research Award and Lecture at the 45th meeting of the Child Neurology Society in 2016 and having an endowed lectureship in his name at the University of Calgary, the Harvey B. Sarnat Developmental Neuroanatomy and Neuropathology Lectureship, since 2013. A Harvey Sarnat Clinical Research Fellowship in Neonatal Neurocritical Care was announced in 2022 by the Section of Neonatology of the University of Calgary.
Target Audience:
Pathologists, Residents, Other – Write In (Required): basic neuroscientists
CanMEDS:
Scholar
Keratan sulfate proteoglycan is not expressed in the human fetal cerebellar system except in pontine nuclei and transitory vermal septa; not in corticospinal fasciculi caudal to internal capsule
Abstract
Objectives. We determined spatial and temporal expression of keratan sulfate (KS) proteoglycan in the cerebellar system, dysgeneses and in white matter fasciculi. KS proteoglycan is an extracellular matrix molecule secreted by astrocytes. KS forms an early template of neuroblastic migration to the cortical plate and some axonal fascicles before axons enter.
Methods. KS immunoreactivity was studied in sections of cerebellar cortex and in deep cerebellar, inferior olivary and red nuclei and white matter in 18 human fetuses 14-41 weeks gestation at autopsy, 6 infants to 2 years, and 9 cerebellar dysgeneses. Synaptophysin expression was compared.
Results. Dentate, inferior olivary and red nuclei are nonreactive at all ages, but pontine nuclei are positive from early 2nd trimester. Cerebellar white matter pathways remain non-reactive throughout fetal and postnatal life. Bergmann glia are nonreactive at all gestational ages. Transitory parasagittal KS septa demarcate vermis/hemispheric boundary. KS is not expressed in Dandy-Walker, Joubert or Chiari malformations, pontocerebellar hypoplasia or cerebellar heterotopia. Axonal fascicles of the corticospinal tract caudal to the internal capsule do not exhibit KS reactivity. Synaptophysin in cerebellar system was normal.
Conclusions. Absence of hindbrain KS contrasts with strong forebrain reactivity. Lack of KS expression in normally developing cerebellum and associated brainstem nuclei except pontine, and its absence in cerebellar dysgeneses implies that KS does not contribute to pathogenesis in cerebellar system malformations. Transitory KS septa define early vermal margins, similar to septa of neuromeric segmentation. The intense KS template of the internal capsule does not extend caudally to brainstem fascicles.