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Embryological Development of CNS
Department of Anatomy and Histology
Faculty of Medicine Brawijaya University
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SKDI 2012
• KELAINAN KONGENITAL SISTEM SARAF
HYDROCEPHALUS
SPINA BIFIDA
CEREBRAL PALSY
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Tingkat Kemampuan 1:
Lulusan dokter mampu mengenali dan menjelaskan gambaran
klinik penyakit, dan mengetahui cara yang paling tepat untuk
mendapatkan informasi lebih lanjut mengenai penyakit tersebut,
selanjutnya menentukan rujukan yang paling tepat bagi pasien.
Lulusan dokter juga mampu menindaklanjuti sesudah kembali
dari rujukan.
Tingkat Kemampuan 2:
Lulusan dokter mampu membuat diagnosis klinik terhadap
penyakit tersebut dan menentukan rujukan yang paling
tepat bagi penanganan pasien selanjutnya.
Lulusan dokter juga mampu menindaklanjuti sesudah kembali
dari rujukan.
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ILUSTRASI
KASUS
• Dokter…anak saya
lahir normal, kenapa
lama kelamaan
kepalanya membesar?
• Penyebabnya apa
dokter?
• Bisa sembuh dokter?
• Kalau dioperasi, dia
bisa jadi anak normal
?
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ILUSTRASI
KASUS
• Dari hasil USG tampak penonjolan berisi kista pada bagian posterior
janin..
• Kemungkinan spina bifida
• Apa itu dokter??
• Penyebabnya apa dokter?
• Bisa dioperasi dokter?
• Anaknya bisa normal dokter?
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ILUSTRASI
KASUS
• Anak saya umur 3 tahun belum
bisa jalan…normalkah dokter?
• Kalau merangkak juga
gerakannya aneh..
• Pernah kejang-kejang..
• Kalau makan, sepertinya ia juga
sulit menelan…
• Dokter :?????
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MARI BELAJAR
TUMBUH KEMBANG CNS
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A little flashback....
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Zygote (fertilized egg)
• Produced from combination of male and female parent
chromosomes
• Mitotic Division Begins
• New Cells called Blastomeres which form a Morula
Two-cell
Stage
Four-cell
Stage
Morula
~3 days
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Blastocyst
• Embryoblast
• Blastocyst
• Trophoblast
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Blastocyst
Uterine stroma
Trophoblast cells
Embryoblast
Blastocyst cavity
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The first week
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The second week:
Bilaminar Embryo
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Embryo has two primary layers: Epiblast & Hypoblast
Cytotrophoblast
Amniotic Cavity
Epiblast
Hypoblast
Primary Yolk Sac
Exocoelomic Membrane
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Gastrulation ….
caused by a proliferation of
epiblast cells
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Third week:
Trilaminar Embryo Develops
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Third week: Trilaminar Embryo Develops
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• Embryo Trilaminar: three
layers between amniotic
cavity and yolk sac
– Ectoderm – future
covering (skin, nails, hair,
but also CNS)
– Mesoderm – future
muscles, bones, heart
– Endoderm – future
digestive tract
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Third week: Trilaminar Embryo Develops
Presomite Embryo – 18 days
Cut edge
of amnion
Neural plate
Primitive pit
Primitive streak
(mesoderm)
Neurulation  formation of the
neural plate18 and neural tube
Third week: Trilaminar Embryo Develops
• Primitive Streak Forms dorsally
• Forms neural tube, notochord (cartilaginous rod, future spine)
and neural crest cells
• Notochord : mesoderm origin
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Presomite Embryo – 20 days
Cut edge
of amnion
Neural groove
Somite
Primitive streak
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Early Highlights
• Day 18 - Neural plate invaginates (encloses) to form neural
groove
• Day 22 - Neural Tube Forms
– Becomes brain and spinal cord
• About the same time, Neural Crest Forms
– Becomes cranial and spinal nerve ganglia
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Neural Tube
•
•
•
•
•
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Cranial 2/3 will form brain
Caudal 1/3 will form spinal cord
Day 25 - Cranial opening closes
Day 27 - Caudal end closes
Problems cause neural tube defects
The walls of the neural tube thicken to form the
brain and the spinal cord
• The neural canal forms the ventricular system of
the brain and the central canal of the spinal cord
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LAYERS OF EARLY NEURAL TUBE
1. Ventricular zone :
ependymocyte,
choroid plexus cells
2. Intermediate zone:
neuroblast, glioblast
3. Marginal zone :
glioblast
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Human Embryo – 22 days
Neural fold
Optic placode
Somite
Cut edge of amnion
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Human Embryo – 23 days
Cranial neuropore
Pericardial bulge
Caudal neuropore
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• Brain has 3 sections
• = Primary brain vesicles
 Prosencephalon/ forebrain
 Mesencephalon/ midbrain
 Rhombencephalon/
hindbrain
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Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Embryology of the brain
• The secondary brain vesicles grow rapidly, especially
the telencephalon, which overlaps the diencephalon
• Telencephalon = lateral ventricles + cerebrum
• Diencephalon = third ventricle + thalamus +
hypothalamus
• Mesencephalon = cerebral aqueduct + midbrain
• Metencephalon = fourth ventricle + pons +
cerebellum
• Myelencephalon = fourth ventricle + medulla
oblongata
Neural Crest Development
• Cranial neural crest cells • Trunk neural crest cells
1. from somite 6 to the most caudal somites and
1. There is a remarkable
migrate
relationship between
2. Trunk neural crest cells differentiate into the
the origin of cranial
following structures:
neural crest cells from
a. Melanocytes
the rhombencephalon
b. Schwann cells
(hindbrain) and their
c. Chromaffin cells of adrenal medulla
final migration into
d. Dorsal root ganglia
pharyngeal arches
2. The rhombencephalon is e. Sympathetic chain ganglia
f. Prevertebral sympathetic ganglia
divided into eight
g. Enteric parasympathetic ganglia of the gut
segments called
(Meissner and Auerbach; CN X)
rhombomeres (R1–R8).
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h. Abdominal/pelvic cavity parasympathetic ganglia.
Maturation of CNS
• At birth, all neurons you will ever have present.
– Only a few exceptions (neurons involved w smell)
• Process of myelination signals onset of mature
function
– Slow process
• Partially completed completed by age 7
• Axons and dendrites not until teens
• Some areas continue to age 70
• Some cells have programmed cell death (Apoptosis)
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Neuron structure
Classification of neurons
Structural classification based on number of processes coming
off of the cell body:
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Histological Differentiation
• Nerve cell : neuroblast
• Glial cells : glialblast
– Astrocytes :
– Oligodendroglial cell :
myelin sheaths
– Microglial cells : appears
in CNS
• Neural Crest Cells 
sensory ganglia of the
spinal cord
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Myelination
• Short Gaps (Nodes of Ranvier) on Axons
– Speed up neural activity
• In CNS, formed by Oligodendrocytes
• In PNS, formed by Neurilemmal or Schwann cells
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Seven Steps of CNS Development
1. Production of initial neurons and glial cells
2. Migration of cells to definitive location
3. Selective gathering of cells to functional group
4. Cytodifferentiation (axon, dendrite, synaptic patterns)
5. Selective death of some cells in groups
6. Outgrowth of axons to specific target cells and
establishment of connections
7. Elimination of certain connections and functional
stabilization of others
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Abnormal Development
Neural Tube Defect :
Abnormal closure of the neural folds in 3rd and 4th
weeks of development
• Anencephaly
– Cerebral Hemispheres reduced or missing
• Spina Bifida
– Spina Bifida Occulta :
• defect in the vertebrae arches, does not involve neural
tissue, lumbosacral region
– Spina Bifida Cystica :
• Neural tissue and/or meningens through defect in the
vertebral arches and skin  cysticlike sac
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Anencephalic Newborn
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Cranium Bifida
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Other Developmental Conditions
• Hydrocephaly
– Enlarged head, brain atrophy mental
deficiency
– Excessive production of CSF or
obstruction of drainage pathways
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Congenital Hydrocephalus
• 1 dari 1000 bayi lahir hidup menderita kelainan ini
• insidens congenital hydrocephalus adalah 0,12-2,5 tiap
kelahiran.
• Gen X-linked, L1CAM, adalah satu-satunya gen yang
diketahui berkaitan dengan perkembangan congenital
hydrocephalus pada manusia.
• Mutasi pada gen tersebut mengakibatkan banyak kasus
hydrocephalus X-linked.
• Kelainan genetic jenis autosomal-recessive juga diketahui
dapat mengakibatkan hydrocephalus pada manusia
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Primary Cilia Dyskinesia
• Infertilitas pd
pria
• Anosmia
• Polycistic
kidney
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Causes of hydrocephalus
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Cerebral Palsy
• brain injury or malformation
• Impairments resulting from cerebral palsy range in severity, usually
in correlation with the degree of injury to the brain.
• The primary effect of cerebral palsy is impairment of :
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muscle tone,
gross and fine motor functions,
balance,
control,
reflexes,
posture.
Oral motor dysfunction, such as swallowing and feeding difficulties,
speech impairment, and poor muscle tone in the face,
– Associative conditions, such as sensory impairment, seizures, and
learning disabilities that are not a result of the same brain injury, occur
frequently with cerebral palsy.
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signs and symptoms CP
• developmental delay.
• (+) abnormal muscle tone, unusual posture,
persistent infant reflexes
• not readily visible at birth, except in some severe
cases, and may appear within the first three to five
years of life as the brain and child develop.
• delivery was traumatic/ Risk factor +observe
carefully
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Cause of CP
• Periventricular Leukomalacia (PVL)
– BRAIN INJURY –DAMAGE TO THE WHITE MATTER BRAIN
TISSUE : cell apoptosis
• BRAIN MALFORMATION OR ABNORMAL BRAIN
DEVELOPMENT Cerebral Dysgenesis
• LACK OF OXYGEN TO THE BRAIN OR ASPHYXIA
Hypoxic-Ischemic Encephalopathy, or HIE, or
Intrapartum Asphyxia
• BRAIN HEMORRHAGE Intracranial Hemorrhage, or
IVH
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Cemungudh !
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