1. CEREBROSPINAL FLUID (CSF) AND THE BLOOD-BRAIN BARRIER (BBB)

2. Textbook of Medical Physiology, Guyton and Hall, Ch. 61
Student Preparation
Textbook of Medical Physiology, Guyton and Hall, Ch. 61

3. Cerebrospinal Fluid
Cerebrospinal fluid (CSF) is a clear fluid present in the ventricles of the brain, the central canal of the spinal cord, and the subarachnoid space.
Normal: almost no blood cells, little protein.

4. CSF Cont.
Its rate of formation, flow, and absorption is sufficiently high to cause its replacement several times daily. Measuring its pressure, performing cell counts, and analyzing levels of various biochemical constituents is accomplished with a spinal tap.

5. CSF Cont.
Injecting radiopaque dyes into the subarachnoid space is the basis of a common neuroradiologic technique called a myelogram. Obstruction of flow of CSF is a common cause of hydrocephalus.

6. CSF Cont.
An understanding of the formation, flow, and absorption of CSF is essential to an understanding of these diagnostic procedures and the pathophysiology of hydrocephalus.

7. Cerebrospinal Fluid
A clear, colorless fluid that surrounds and permeates the CNS. Offers support, protection and nourishment.
Functions:
Protection of cranial contents
Modulates pressure changes (same specific gravity as brain)
Serves as a chemical buffer to maintain constant ionic environment
Serves as a transport medium for nutrients and metabolites, endocrine substances and even neurotransmitters

8. Location of CSF Two lateral ventricles Third ventricle
Fourth ventricle
Spinal cord central canal
Subarachnoid space
Continuous with extracellular fluid of brain parenchyma

10. Formation of CSF
Choroid plexuses of lateral, third and fourth ventricles
Ependymal lining of ventricular system
Pia-glial membrane
Blood vessels

11. Formation of CSF
Cells are believed to actively secrete Na+ into the ventricular system in exchange for K+. Sodium ions electrically attract Cl- and osmotically draw water from the blood vascular system to constitute the CSF.

12. Composition of CSF

13. Circulation of CSF Due to pulsation of blood in choroid plexus
Due to pulsation of ependymal cells
Lateral ventricles interventricular foramen of Monroe third ventricle
mesencephalic aqueduct (aqueduct of Sylvius) fourth ventricle spinal cord central canal; also, out the lateral apertures to the subarachnoid space to the venous system

14. Absorption of CSF
Through the arachnoid villi, a protrusion of arachnoid membrane into the central venous sinus and other sinuses
A valve opens when CSF pressure exceeds venous pressure
Absorption by veins and capillaries of CNS

15. CSF Pressure Dog - 170 mm H2O Cow - 200 mm H2O Horse - 400 mm H2O
Subarachnoid hemorrhage blocks absorption, raises pressure
Congenital excessive formation or blockage to flow raises pressure
Regulated by rate of absorption and rate of formation.
Brain tumors lower absorption & raise pressure
Inflamed meninges can cause excessive formation & raise pressure

16. Jugular compression maneuver (Queckenstedt maneuver)
Compress jugular veins in neck - increases CSF pressure at the cerebellomedullary cistern and the lumbar cistern (normal)
Decreased pressure at lumbar cistern indicates blockage of spinal central canal

17. Cerebrospinal fluid collection

18. Cerebrospinal fluid collection
Small animals: atlanto-occipital (cerebellomedullary) cistern
neck

19. Cerebrospinal fluid collection
Large animals
cerebellomedullary cistern
Lumbar cistern (L5-L6)

21. CSF collection

22. Dog Lumbar Myelogram

23. Hydrocephalus (water on the brain)
An abnormal increase in the volume of CSF
Symptoms: depression, sleep, changes in behavior, spastic paresis, papilledema, bulging of skull in young, behavioral change, pacing, head pressing, seizures, cranial nerve deficits, vestibular signs

24. Hydrocephalus
Communicating – due to excessive formation of CSF or lack of absorption
Non-communicating – due to obstruction of flow through ventricle system

25. Ventriculoperitoneal Shunt

26. Coup – Coup-Contrecoup Closed Head Injuries
With a blow to the
back of the
head, the forehead
strikes the surface
(coup), then the
brain bounces
back against
rear skull
(contrecoup)
Coup
Coup-contrecoup

27. Blood-Brain Barrier (BBB)
Direct injection of large molecules (e.g., a dye) into the venous system will often penetrate all tissues except the brain. This observation led to the notion of a physiological barrier to flow of substances from blood to brain tissue – the blood brain barrier.
The BBB functions to preserve a stable environment for neurons and glia of the CNS

28. Differences between brain and general capillaries
General capillary
small solutes can diffuse through intercellular clefts
pinocytosis independent of molecular size (pass large molecules)
fenestrated
Brain capillary
tight junctions
reduced pinocytosis
no fenestra
astrocyte foot processes

29. General vs. Brain Capillaries

30. Brain capillary Tight junctions Surrounded by astrocytes Few vesicles
Carrier mediated transport of glucose and amino acids

31. Blood-Brain Barrier Lipid soluble molecules will cross
Negatively charged molecules cross more freely than positively charged ones
High CO2/low O2 produce vasodilation and decrease resistance of BBB
Injury or inflammation decreases resistance of BBB (allows some antibiotics to be used for treatment)

32. Blood-Brain Barrier (BBB)
Selected brain areas are not protected by the BBB – the circumventricular organs (CVO) bordering on the 3rd and 4th ventricles
parts of the hypothalamus - median eminence
neurohypophysis
pineal gland
area postrema
subfornical organ
subcommissural organ

33. Blood – CSF Barrier Barrier from blood to the CSF
Similar structural mechanism to the BBB