Ventricle

and
Blood Brain Barrier

dr.Aris Widayati,Sp.S
dr. Nia Kurnianingsih, M.Biomed
 LEARNING OBJECTIVES

1. Comprehensive understanding of the protection layer on the brain

2. Comprehensive understanding of the ventricles: the structure, flow
and functions
3. Comprehensive understanding of cerebrospinal fluid: production,
absorption and functions
4. Comprehensive understanding of the blood-brain barrier: structure
and functions
5. Comprehensive understanding of the molecules that easily pass
through the blood-brain barrier
Protection and Nourishment of the brain

• Central nervous tissue is very delicate.

• This characteristic, coupled with the fact that damaged
nerve cells cannot be replaced, makes it imperative that
this fragile,
• Irreplaceable tissue be well protected.
Four major features help protect the
CNS from injury:

Hard &
Bony Meningen
structure

Blood brain
CSF
barrier
Protection layers of Brain

P
 VENTRICLE

• The cerebral ventricles are a series of interconnected cavities, fluid-

filled spaces that lie in the core of the forebrain and brainstem
• Composed of : 2 lateral ventricles (largest)
1 third ventricle
1 fourth ventricle
• The choroid plexuses are located in the ventricles produce CSF
 Struktur sistem ventrikel
• Ventrikel lateralis
cornu anterior
cornu posterior
• Ventrikel ketiga
berada diantara kedua bagian dienchepalon
• Ventrikel empat
membentang dari pon ke medulary
• Ventrikel ke lateralis berhubungan dengan ventrikel ketiga melalui :
for. Internventrikularis (for.monro)
• Ventrikel ketiga berhubungan dengan ventrikel ke empat melalui
akuaduktus serebri
• Ventrikel ke empat berhubungan dengan ruang subarachnoid
melalui:
- 1.foramen magendi (apertura mediana)
- 2 foramen luschka (apertura lateralis)
 Sirkulasi dan resorpsi cairan
serebrospinal
• Sifat CSF
- jernih, hanya mengandung beberapa sel (4/micro liter),sedikit
protein.
- Disekresi aktif oleh plexus choroideus (terutama di ventrikel
lateralis)
- Volum CSF
tiap 24 jam dihasilkan 400 – 500 ml
yang berada di sirkulasi : 130-150 ml
-Tekanan CSF (tidak sama dengan TIK) pada posisi supinasi : 70-120
mmH2O
 Resorbsi
• CSF di resobsi di intrakranial dan sepanjang medula
spinalis
• Sistem resobsi ini antara lain:
- Vili granulasiones arakhnoidae yg ada di sinus sagitalis
superior :CSF dari ruang subarakhnoid -masuk ke
aliran darah
- Sisanya di Perineural saraf kranialis dan saraf spinalis
 melewati ependima dan kapiler leptomenimeningen
 CEREBROSPINAL FLUID
FUNCTION
1
• Protection from mechanical trauma
• Cerebrospinal fluid (CSF) surrounds and cushions the brain and spinal cord.
• The CSF has about the same density as the brain itself, so the brain
essentially floats or is suspended in this special fluid environment.
• The major function of CSF is to serve as a shock-absorbing fluid to prevent
the brain from bumping against the interior of the hard skull when the head
is subjected to sudden, jarring movements.
 CEREBROSPINAL FLUID
FUNCTION
2
• Nutrition and metabolite exchanges
• Important role in the exchange of materials between the neural cells and
the interstitial fluid surrounding the brain.
• The composition of the brain interstitial fluid is influenced more by
changes in the composition of the CSF than by alterations in the blood.
• Materials are exchanged fairly freely between the CSF and brain
interstitial fluid, whereas only limited exchange occurs between the blood
and brain interstitial fluid.
NORMAL CHARACTERISTIC OF CSF

• Colorless
• Volume : 150 ml
• Production rate : 0,5 ml/minute (500 ml/day)
• Composition : Protein 15-45 mg/100 ml
Glucose 50-85mg/100 ml
Chloride 720-750 mg/100 ml
Cell count 0-3 limfosit/mm3
Tabel 10.1
 BBB
• To maintain normal brain function, the neural environment must be
preserved within a narrow homeostatic range
• this requires a tight regulation of transportation of cells, molecules
and ions between the blood and the brain
• Three barrier layers contribute to the separation of the blood and
neural tissues:
(1) a highly specialized endothelial cells (EC) layer comprising the
blood-brain barrier (BBB) and partitioning the blood and brain
interstitial fluid
(2) The blood-CSF barrier (BCSFB) with the choroid plexus epithelium
which secretes CSF into the cerebral ventricles
(3) the arachnoid epithelium separating the blood from the
subarachnoid CSF
 BLOOD BRAIN BARRIER
The blood–brain barrier (BBB) is a dynamic and functional neurovascular
unit comprised of the capillary endothelium, astrocytes, pericytes, and
extracellular matrix.
• The BBB components include the EC layer and its basement
membrane
adjoined by tight cell-to-cell junction proteins
with specific transport mechanisms and pinocytic vesicles
• the endothelium is surrounded by pericytes and astroglial foot
processes forming continuous stratum  separates blood
vessels from brain.
 The basement membrane
• a 30 to 40-nm thick lamina
• composed of collagen type IV, heparin sulfate proteoglycans,
laminin, fibronectin, and other extracellular matrix proteins
• . Transmembrane proteins :
-junctional adhesion molecule: occludin, and claudins
-cytoplasmic accessory proteins :zonula occludens-1 and -2, cingulin,
AF-6, and 7H6 establish the tight junctions between adjacent
endothelial cells
• junctional adhesion molecules maintain tight junction properties,
• claudins facilitate tight barrier capabilities
• occludins and zonula occludens-1 regulate targeted signaling
• Pericytes are enveloping brain microvessels and capillaries and are
found in close proximity to astrocytes and neurons.
• The ratio of pericytes to endothelial cells is assessed to be 1:3.
• pericytes seems to play a critical role in the formation and
maturation of the BBB during development and regulation of tissue-
survival
• Astrocytes play important roles in maintenance of the BBB in
homeostasis of extracellular concentration of transmitters,
metabolites, ions and water
• serve as stem cells during development and provide for templates
for migratory neuronal streams.
• Interaction between astrocytes and neurons determine synaptic
transmission, clearance of neurotransmitters, plasticity
Physiology of the blood-brain
barrier
• Each of the three main CNS interface layers: the BBB, choroid
plexus epithelium and the epithelium of the arachnoid mater,
functions as a physical, transport, metabolic, and immunologic
barrier.
• The barriers are permeable to O2 and CO2 and other gaseous
molecules such as helium, xenon, N2 and many gaseous
anesthetics water
• Lipid soluble substances can pass the barrier by diffusion
• Large molecules (e.g. peptides and proteins) enter the brain in a
restricted and regulated manner by adsorptive and receptor-
mediated transcytosis
• the barriers also regulate the recruitment and entry of leukocytes
and innate immune elements and involve in both the reactive and
surveillance functions of CNS immunity.
 BLOOD BRAIN BARRIER

• The brain is carefully shielded from harmful changes in the blood by a

highly selective blood–brain barrier (BBB).
• Unlike the rather free exchange across capillaries elsewhere, only
selected, carefully regulated exchanges can be made across the BBB.
• For example, even if the K level in the blood is doubled, little change
occurs in the K concentration of the fluid bathing the central neurons.
• This is beneficial because alterations in interstitial fluid K would be
detrimental to neuronal function.
 BLOOD BRAIN BARRIER

• Lipid-soluble substances such as O2, CO2, alcohol, and steroid hormones

penetrate these cells easily by dissolving in their lipid plasma membrane.
• Small water molecules also diffuse through readily, by passing between
the phospholipid molecules of the plasma membrane or through
aquaporins (water channels)
• Smaller peptides may cross the BBB by either nonspecific fluid-
phase endocytosis
 BLOOD BRAIN BARRIER

• By strictly limiting exchange between the blood and brain, the BBB
protects the delicate brain from chemical fluctuations in the blood and
minimizes the possibility that potentially harmful blood-borne substances
might reach the central neural tissue.

• It further prevents certain circulating hormones that could also act as

neurotransmitters from reaching the brain, where they could produce
uncontrolled nervous activity.
 BLOOD BRAIN BARRIER

• On the negative side, the BBB limits the use of drugs for the treatment of
brain and spinal cord disorders because many drugs are unable to
penetrate this barrier.

• Certain areas of the brain, most notably a portion of the hypothalamus,

are not subject to the BBB.

• Functioning of the hypothalamus depends on its “sampling” the blood and

adjusting its controlling output accordingly to maintain homeostasis.
• Appropriately, these hypothalamic capillaries are not sealed by tight
junctions.
 REFERENCE

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2nd edition.Sinauer Associates;
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• Hawkins, Richard A., O’Kane, Robyn L., Ian A. Simpson, and Juan R.Vin˜az.2006. Structure of
the Blood–Brain Barrier and Its Role in the Transport of Amino Acids.The Journal of
Nutrition.218s-226s
• Structure and function of the blood–brain barrier
• Abbott ,N. Joan., Adjanie A.K. Patabendige, Diana E.M. Dolman, Siti R. Yusof, David J.
Begley.2010.Neurobiology of Disease. 37:13–25
• Sherwood, Lauralee.2010.Human Physiology: From Cells to Systems, Seventh
Edition.Brooks/Cole.USA
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