CSF and Blood Brain Barrier

Cerebrospinal fluid (CSF)

From: Laterra J et al., in Basic Neurochemistry

4
Cerebro spinal fluid production & Circulation
Clear, colourless, alkaline fluid is found in
 Ventricles of brain
 Cisterns around brain
 Subarachnoid space around
brain and spinal cord
Choroid Plexus :
Temporal horn of each lateral ventricle
Choroid plexus
present in Posterior portion of III ventricle
Roof of IV ventricle
 Vascular fringes of piamater break up into complex
capillary network covered by cuboidal epithelial cells,
 Cells contain mitochondria, granules, vesicles indicating
involvement in active metabolic process (secretory)
Choroid
Plexus

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Arachnoid villi
 Microscopic finger like projections of arachnoid
membrane into walls of venous sinuses.
 Lined by endothelial cells
 Large conglomerates of villi called arachnoid
granulations / pachionian bodies
 Electron microscopic study shows transcellular
channels / pores in lining endothelium which allows
free absorption of CSF, proteins.
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Perivascular space :
Blood vessel entering brain substance will carry
with it sleeve of arachnoid immediately surrounding the
vessel and sleeve of pia more externally. Extension of
SAS around the vessel known as PV space / virchow robin
space.
Products of metabolism, inflammatory exudates
pass from brain substance into perivascular space, to
enter CSF in subarachnoid space.
Formation of CSF
 Active secretion by choroid plexus
 Trans ependymal diffusion of brains interstitial
fluid into ventricles (minimal)
Secretion :
Na+ K+ ATPase, carbonic anhydrase takes part in
Active transport of Na+ occurs through epithelial cells
lining choroid plexus

Na+ will carry Cl- with it.

Na+ & Cl- increase the quantitiy of osmoticaly active

substances in CSF, which cause immediate osmosis of
water through the membrane.
Less important transport process move small amount
of glucose into CSF, K+ & HCO3- out of CSF
 Production of CSF

Net transport of Na+ and Cl- across

the epithelium results in the
secretion of CSF.

Cl- efflux from the epithelium to

CSF is mediated by a cotransporter.

The generation of H+ and HCO3 by

carbonic anhydrase is important in
the secretion of CSF.

From: Laterra J et al., in Basic Neurochemistry

13
Resulting characteristics of CSF :
Osmotic pressure & Na+ equal to plasma
Cl- 15% greater than plasma
K+ 40% less than plasma
Glucose 30% less than plasma
 CSF formation
• 50% by choroid plexuses in the ventricles
• 40% by meningeal blood vessels and
ependymal lining of ventricles
• 10% by brain and spinal cord blood vessels
• Absorption
• 80% by arachinoid villi into venous sinuses
and spinal veins
• 20% by cervical lymphatics and perivascular
spaces
 CSF
• CSF is a clear colorless, isotonic alkaline fluid,
almost protein and cell free and contains less
glucose and k+ than plasma.
• Volume- 130-150ml
• Daily secretion-500-550ml
• Rate of formation-0.2-0.3ml/min
• Pressure-130mm of water
Circulation :
From lateral ventricles through foramen of monro /
inter ventricular foramen to III ventricle
From III ventricle through cerebral aqueduct of sylvius
to IV ventricle
From IV ventricle leaves via median and lateral
apertures of magendie and luschka to reach SAS covering
cerebrum and spinal cord
After bathing surface of spinal cord and base of brain
CSF passes upward over convexity of hemispheres to be
absorbed in intracranial venous sinuses.
21
Absorption :
4/5th of CSF absorbed via cerebral arachnoid villi
1/5th spinal arachnoid villi
Hydrostatic pressure in sub arachnoid space is higher than
in dural sinuses facilitates fluid movement
Small amount pass into perivascular space, sheath of
cranial nerves
Characteristics of CSF
pH 7.31 – 7.34
Specific gravity - 1005
Osmolarity 290 – 295 mosm /l
Volume 70-120 ml (25ml ventricles 25 ml spinal theca)
 Force of circulation
• Movement of the CSF is by pulsating blood
vessels, respiration and changes of posture
• CSF is secreted continuously at a rate of about
0.5ml per minute i.e. 720 ml per day
• Total CSF in the brain 120 ml
• CSF pressure can be measured by attaching a
vertical tube to the lumbar puncture needle –
10 cm water

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Rate of formation : 0.35 ml / min
500 ml / day
Constituents mg / dl Plasma CSF
Protein 7000-8000 20-40
Glucose 70-110 40-70
Nacl 560-630 720-750
Cholestrol 130-230 Nil
Urea 20-40 10-30
Creatinine 0.6 – 1.5 0.5 – 1.9
Uric acid 2–8 0.5 – 2.5
Phosphates 2- 4 1.2 – 2.0
 Constituent osmol / litre Plasma CSF
Na+ 136 – 145 137-145
K+ 3.5 – 5.0 2.7 – 3.9
Ca2+ 4.5 – 5.5 2.1 – 3.0
Mg 2+ 1.3 – 2.1 2.0 – 2.5
Cl- 98 – 106 116-122
HCO3- 21-27 20-24
pH units 7.36 – 7.44 7.31 – 7.34
Osmolarity 290 – 295 285-295

CSF Pressure :
Lateral recumbent - 60 – 180 mm H2O
Shifting - 300 mm H2O
 Hydrocephalus

• Obstructive hydrocephalus
– Congenital malformations
– After inflammation or hemorrhage
– Mass lesions

• Communicating hydrocephalus
– Overproduction of CSF
– Defective absorption of CSF
– Venous drainage insufficiency
Normal Brain

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Normal Ventricles

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Hydrocephalus

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Hydrocephalus

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Normal ventricles and hydrocephalus

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 Cerebral Edema
• Vasogenic edema: A state of increased
extracellular fluid volume; Brain tumor, abscess, infarct,
hemorrhage; glucocorticoids, hypertonic solutions
• Cytotoxic edema: The swelling of cellular
elements; Hypoxia/asphyxia, water intoxication, meningitis,
encephalitis, Reye’s syndrome
• Interstitial edema: Attributed to increased
water and sodium in periventricular white
matter; Obstructive hydrocephalus; Surgical shunting, acetazolamide
 CSF sampling
• Contraindication or precaution in ↑ICP
• Pressure from lumbar puncture: 65-195 mm CSF (H 2O), or 5
– 15 mmHg
• Cells: 0; ↑ by inflammation, tumor, or other cerebral
damage
• Protein: < 35 mg/dl; ↑ in blockage or increased BBB
permeability.
• Glucose: > 40 mg/dl; ↓ in meningeal tumor, fungal or TB
infection, sarcoidosis
• Appearance: not cloudy or xanthochromic
 Function of CSF
• Maintenance of a constant external
environment for neurons and glia
• Mechanical cushion to protect the brain and
provide buoyancy to the heavy brain (1400
g)
• Serves as a lymphatic system and a conduit
for neuropeptides
• pH of CSF regulates pulmonary ventilation
and CBF
 Function of CSF
• Maintenance of a constant external
environment for neurons and glia
• Mechanical cushion to protect the brain and
provide buoyancy to the heavy brain (1400
g)
• Serves as a lymphatic system and a conduit
for neuropeptides
• pH of CSF regulates pulmonary ventilation
and CBF
 Functions and Properties of the BBB
• General Properties of the BBB
1. Large molecules do not pass through the BBB easily.
2. Low lipid (fat) soluble molecules do not penetrate into the brain.
However, lipid soluble molecules rapidly cross the BBB into the brain.
3. Molecules that have a high electrical charge to them are slowed.
• Therefore:
– The BBB is selectively permeable to :Oxygen, Carbon dioxide and
glucose
– The BBB is not permeable to
hydrogen ions
 Function of CSF
• Maintenance of a constant external
environment for neurons and glia
• Mechanical cushion to protect the brain and
provide buoyancy to the heavy brain (1400
g)
• Serves as a lymphatic system and a conduit
for neuropeptides
• pH of CSF regulates pulmonary ventilation
and CBF