CSF AND BLOOD BRAIN

BARRIER
• DR. OKUNA.
OUTLINE
• Functions of the CSF
• Formation and absorption of the CSF
• Flow and composition of the CSF
• Pressure of the CSF
• Blood-Brain Barrier (BBB)
• Function of the BBB
CEREBROSPINAL FLUID

• A specialized extracellular fluid in the ventricles and the SA

space
• CSF fills the ventricles, the cisterns and SA space
• Capacity: 1600-1700ml
• Volume of CSF: 150ml
• Rate of CSF production: 550ml/d
• Turn over rate: 3.7 times a day
FUNCTION OF THE CSF
• Mechanical protection of the brain from trauma (Cushioning) 
• Provide Buoyancy for the brain: weight reduction from 1400g
in air to 50g in CSF
• Provides a constant and controlled ionic extracellular
environment 
• Acid-base regulation 
• Nutrition
• Nourishes the brain, and Removes waste 
• Acts as reservoir to regulate contents of the cranium 
• Serves as clinical diagnostic
• convey messages? (hormones/releasing
factors/neurotransmitters)
FORMATION OF THE CSF

• Formed mainly in the choroid plexus: 50-70%

• Also secreted by ependymal surfaces of all
ventricles, and by arachnoid membranes.
• Formed continuously in two stages:
1.Active secretory process
2.Secretion of water and ions across the
choroidal epithelium
CSF PRODUCTION
• The secretion of fluid by the
• 70 % CSF produced in
choroid plexuses of lateral,
third and fourth ventricles
• produced at rate of 500 cc/day
or approximately 20cc/hour
(0.3-0.5 cc/kg/hr)
• eliminated by being absorbed
into the arachnoid villi -->
dural sinus --> jugular system
choroid plexus depends on the
active Na+-transport across
the cells into the CSF. The
electrical gradient pulls along
Cl-, and both ions drag water
by osmosis. The CSF has
lower [K+], [glucose], and
much lower [protein] than
blood plasma, and higher
concentrations of Na+ and Cl-.
The production of CSF in the
choroid plexuses is an active
secretory process, and not
directly dependent on the
arterial blood pressure.
BLOOD-CSF BARRIER

• The barrier between cerebral capillary blood and CSF

is the Choroid Plexus
• This barrier consists of: capillary endothelial cells and
BM; neuroglial membrane; and epithelial cells of ChP.
• Capillary endothelium is fenestrated, but ChP
epithelium is relatively impermeable due to apical
tight junctions, ultrafiltration and secretion are
important for the transport of selected constituents of
CSF
 CHOROID PLEXUS
• A rich network of blood vessels
covered by ependymal cells
projecting into the temporal horn of
each ventricle, the posterior portion of
third ventricle, and the roof of fourth
ventricle
• Formed by invagination of vascular
Pia mater into the ventricular cavity
AT THE BASAL SURFACE

• ATP pumps at the BM move Na into the cell,

and K and H out of the cell into the stroma
• Cl with Na move into the epithelial cells of
the ChP
• HCO3 and H ions are formed within the
epithelial cell
 AT THE APICAL SURFACE

• ATP pumps secrete Na into the CSF, and move K into the cell
• Cl and HCO3? move passively along the electrochemical
gradient into the CSF
• Water moves into the CSF due to osmotic gradient
• Glucose enters the CSF by a facilitated transport mechanism
• Protein enters CSF by passage thru junctions of epithelial
cells and by vesicular transport across the epithelium
COMPOSITION OF THE CSF

• Composition is essentially the same as brain

ECF (15% of brain volume)
• Water: >99%. Organic/non-organic/cells:
<1%
• Organic: prtns, AA, glucose, cholesterol, urea,
uric acid, creatinine, lactic acid
• Inorganic: Na, Ca, Mg, Cl, Ph, S, HCO3, K
 CSF SPACES

• Two lateral ventricles

• Foramina of Monroe
• Third ventricle
• Cerebral aqueduct of Sylvius
• Fourth ventricle
• Central canal of spinal cord
• Central foramen of Magendie and lateral
Foramen of Luschka
• Subarachnoid space
CSF CIRCULATION
lateral ventricles--> foramen
of Monro third ventricle -->
aqueduct of Sylvius --> fourth
ventricle --> foramina of
Magendie and Luschka -->
subarachnoid space over brain
and spinal cord -->
reabsorption into venous sinus
blood via arachnoid
granulations
 REABSORPTION OF THE CSF
• Absorbed thru the arachnoid villi, microscopic figer-like inward projections
of arachnoid membrane, through the walls into the venous sinuses
• Located within the dural walls of the sagittal and the sigmoid sinuses and in
the dural walls of spinal cord
• Endothelial cells have vesicular passages large enough to allow free flow of
CSF, dissolved protein molecules and cells (WBCs, RBCs)
• 85-90% of CSF is absorbed by intracranial arachnoid villi; 10-15% by spinal
arachnoid villi
CSF PRESSURE

• CSF pressure is normally 7.0-18.0 cmH2O (5-15

mmHg)
• Formation is independent of intra-ventricular pressure
• Absorption is proportional to the pressure
• At 11 cmH2O = formation and absorption are equal
• Below 6.8 cmH2O = absorption stops
CSF PRESSURE

• Normal ICP (5-15mmHg)

• If increased up to 20mmHg there is a minimal effect
on formation as long as CPP is above 70mmHg;
• But reabsorption increases by increased pinocytosis
and opening of intercellular spaces.
• If CSF pressure rises >30mmHg, the resistance to
reabsorption decreases; if CSF pressure <7mmHg,
minimal reabsorption occurs
BLOOD BRAIN BARRIER
THE CONCEPT

• The tight junctions between capillary

endothelial cells in the brain and between
the epithelial cells in the choroid plexus
effectively prevent proteins from entering
the brain in adults and slow the penetration
of some smaller molecules as well.
WHY BBB & BCB

• Controlled external milieu of neurons –needed for

excitability of neurons
• Protection against infections
• Protection against autoimmune responses
• Protection against cerebral oedema (skull is a closed box-no
volume increase possible)
 LAYERS OF THE BBB
• The blood-brain barrier is formed by the capillaries in the
brain
• Capillary endothelial cells have the following features:
1.Tight junctions (zona occludens)
2.Absence of fenestrations
3.A high content of mitochondria
• On the BM of the endothelium, there is a perivascular area
of closely applied foot processes of the astrocytes with
intercellular clefts or channels
CELLS INVOLVED

1. Endothelial cell
2. Astrocyte
3. Pericyte
4. Neuron
TRANSPORT MECHANISM

• Water, CO2 and O2 penetrate with ease (passive)

• Proteins and polypeptides do not
• Glucose diffuses across the BBB very slowly
• Glucose entering CSF has specific transporters
(GLUT1)
• Other specific transporters: thyroid hormone, organic
acids, and amino acids
 BACK-TRANSPORT
• Some drugs and peptide permeate into the endothelial
cells, but are promptly transported back to blood
• P-glycoprotein is an ATP binding cassette transporter,
a non-specific multidrug transporter in the apical
membrane
•
CIRCUMVENTRICULAR ORGANS

• Areas in the brain that do not have blood-brain barrier

• These areas include:
1. Posterior pituitary (NH)
2. Part of the hypothalamus
3. Area postrema (AP)
4. Organum vasculosum of the lamina terminalis (OVLT)
5. Subfornical organ (SFO)
CIRCUMVENTRICULAR ORGANS

• Some function as “neurohemal organs”: areas in which

polypeptides secreted by neurons enter the circulation
• Some contain receptors and function as chemoreceptor zones,
so that substances in blood can trigger changes in brain without
penetrating blood brain barrier
• Examples: vomiting response in area postreama, angiotensin II
produces neutrally mediated increase in BP by acting on SFO
and OVLT, circulating interleukin-1 produces fever by acting
here
DEVELOPMENT OF THE BBB

• Studies on animals suggest that BBB is immature

at birth
• In human, there is no passive permeability of the
normal human neonatal BBB
• However, high levels of bilirubin can lead to
damage of the basal ganglia (Kernicterus) in
neonates and also hepatic encephalopathy in
children with Criglar-Najjar syndrome
CLINICAL IMPLICATIONS

• Difference between drugs and their acid precursors in

permeability
• BBB tends to break in areas of infection or injury
• Tumors develop new vessels, which may be
fenestrated, no tight junctions, and no astrocyte contact
• Sudden marked increase in BP or hypertonic fluids
may temporarily disrupt the BBB
REFERENCES

• Ganong’s review of medical physiology, 26th edition

• Guyton and Hall textbook of medical physiology, 14th
edition
• Physiology, Costanzo, 6th edition
• Principles of Physiology for anesthetist, 3rd edition
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53266
71/