CSF & BBB (blood brain barrier)

Question 1

Cerebrospinal fluid and blood-brain barrier

The brain and the spinal cord are enveloped by three sheets of connective tissues, the ?:

• ? (thick layer of fibroblasts; it fuses with the bone inner surface of skull bones)
• ? (spiderweb-like; thin layer of fibroblasts that trap ? between it and pia mater)
• ? (single layer of fibroblasts)

Answer 1

Cerebrospinal fluid and blood-brain barrier

The brain and the spinal cord are enveloped by three sheets of connective tissues, the meninges:

• Dura mater (thick layer of fibroblasts; it fuses with the bone inner surface of skull bones)
• Arachnoid mater (spiderweb-like; thin layer of fibroblasts that trap CSF between it and pia mater)
• Pia mater (single layer of fibroblasts)

Question 2

Cerebrospinal fluid and blood-brain barrier

The cerebrospinal fluid (CSF) is a ? fluid present in the ? of the brain, in the ? of the spinal cord, and in the ? space (brain and spinal cord)

CSF functions:
* To ? the brain (? blows to the head)
* Maintaining a consistent ? for the ? and ? cells
* ? control system for the removal of potentially ?
* Distribution medium for ? hormones and ? factors that are secreted into the CSF

Cerebrospinal fluid and blood-brain barrier

CSF is produced ** ? ** in choroid plexus located in ? of the four ventricles (in the floor or roof) at a relatively constant rate

The lateral ventricles are respectively located in the ? cerebral hemispheres, the third ventricle is found at the ? of the diencephalon, and the fourth ventricle is located between the ? and the ? surface of the hindbrain (pons and medulla)

Answer 2

Cerebrospinal fluid and blood-brain barrier

The cerebrospinal fluid (CSF) is a clear fluid present in the ventricles of the brain, in the central canal of the spinal cord, and in the subarachnoid space (brain and spinal cord)

CSF functions:
* To cushion the brain (buffering blows to the head)
* Maintaining a consistent extracellular microenvironment for the neurons and glia cells
* waste control system for the removal of potentially harmful cellular metabolites
* Distribution medium for peptide hormones and growth factors that are secreted into the CSF

Cerebrospinal fluid and blood-brain barrier

CSF is produced specialized ependymal cells in choroid plexus located in each of the four ventricles (in the floor or roof) at a relatively constant rate

The lateral ventricles are respectively located in the two cerebral hemispheres, the third ventricle is found at the midline of the diencephalon, and the fourth ventricle is located between the cerebellum and the dorsal surface of the hindbrain (pons and medulla)

Question 3

Cerebrospinal fluid and blood-brain barrier

• The plexuses consist of tufts of capillaries covered by a layer of * ? * that form a selective, ? barrier to the secretions of the leaky capillaries and to other surrounding ? (e.g., CSF, extracellular fluid)
• Relevant processes:
   active transport of ?
  and ? into the ?
   water follows the ? passively into the ventricle
   ? of some potentially harmful waste products

Answer 3

Cerebrospinal fluid and blood-brain barrier

• The plexuses consist of tufts of capillaries covered by a layer of * ependymal cells * that form a selective, tight-junction barrier to the secretions of the leaky capillaries and to other surrounding fluids (e.g., CSF, extracellular fluid)
• Relevant processes:
   active transport of sodium ions (Na) and chloride (Cl-) into the ventricles
   water follows the NaCl passively into the ventricle
   metabolization of some potentially harmful waste products

Question 4

Cerebrospinal fluid and blood-brain barrier

PICS IN ANS

• CSF flows down a pressure gradient from its site of formation at the ? through the ventricular system and ? space into the venous system
• Lateral ventricles -> into the ? ventricle through the ? foramina (foramina of ?) -> through the cerebral ? (aqueduct of ?) of the midbrain -> into the ? ventricle -> into the subarachnoid space through foramina of ?

Answer 4

Cerebrospinal fluid and blood-brain barrier

PICS IN ANS

• CSF flows down a pressure gradient from its site of formation at the choroid plexus through the ventricular system and subarachnoid space into the venous system
• Lateral ventricles -> into the third ventricle through the interventricular foramina (foramina of Monro) -> through the cerebral aqueduct (aqueduct of sylvius) of the midbrain -> into the 4th ventricle -> into the subarachnoid space through foramina of Luschka

Question 5

Cerebrospinal fluid and blood-brain barrier
CSF sampling

CSF can be sampled by placing a stilettoed ? needle into the ? space

In humans -> in the ? spinal column
In most veterinary species -> between the skull and the first ? vertebra (atlas) in anesthetized animals

Normal CSF is ? and ?. Turbidity indicates increased cellularity, and a ? tint suggests the presence of blood

Answer 5

CSF sampling

CSF can be sampled by placing a stilettoed spinal needle into the subarachnoid space

In humans -> in the lumbar spinal column
In most veterinary species -> between the skull and the first cervical vertebra (atlas) in anesthetized animals

Normal CSF is clear and translucent. Turbidity indicates increased cellularity, and a pink tint suggests the presence of blood

Question 6

 CSF absorption into the ? system takes place in ?-lined venous sinuses within the ?

Most of the fluid is absorbed from the ? space into the ** ? sinuses through ? **(small, fingerlike projections of the arachnoid membrane that poke through the walls of the sinus)

 Absorption appears to be ?-dependent and is ?

 CSF is produced at a rate of about ? mL/hr in cats, about ? mL/hr in dogs and about ? mL/hr in humans

 The entire volume of CSF is replaced a few or several times a day?

Answer 6

 CSF absorption into the venous system takes place in dura-lined venous sinuses within the skull

Most of the fluid is absorbed from the subarachnoid space into the ** dural sinuses through arachnoid villi **(small, fingerlike projections of the arachnoid membrane that poke through the walls of the sinus)

 Absorption appears to be pressure-dependent and is unidirectional

 CSF is produced at a rate of about 1 mL/hr in cats, about 3 mL/hr in dogs and about 20 mL/hr in humans

 The entire volume of CSF is replaced a few or several times a day? SEVERAL TIMES

Question 7

Cerebrospinal fluid and blood-brain barrier

Hydrocephalus:
Increased CSF volume in the skull, often associated with an ? volume and ? pressure

Non-communicating hydrocephalus:
Normally caused by an obstruction to ? (? cerebral aqueduct or blocked exits from the ?)
-> This causes the ? regions inside the brain to expand at the expense of the surrounding brain tissue, and ? pressure rises

Communicating hydrocephalus:
? of absorption (can be secondary to ? or ?)
-> This can increase CSF volume in the subarachnoid space, which increases pressure on the ? surface of the brain and increases ? pressure.

Answer 7

Hydrocephalus:
Increased CSF volume in the skull, often associated with an increased ventricular volume and increased intracranial pressure

Non-communicating hydrocephalus:
Normally caused by an obstruction to CSF flow (narrow cerebral aqueduct or blocked exits from the fourth ventricle)
 This causes the ventricular regions inside the brain to expand at the expense of the surrounding brain tissue, and intracranial pressure rises

Communicating hydrocephalus:
Impairment of absorption (can be secondary to meningitis or hemorrhage)
 This can increase CSF volume in the subarachnoid space, which increases pressure on the outside surface of the brain and increases intracranial pressure.

Question 8

 The blood-brain barrier consists of specialized capillary ? cells that are lined by the ?, astrocytic endfeet, ? and ? cells.

In brain capillaries, passage through intercellular clefts is blocked by ?, and exchange of ? is highly selective.

The blood brain barrier–histological characteristics:

• Few or no ?
• ? very uncommon to observe at
  the BBB
• ? junctions
• ? and ? side of the
  endothelium (polarized)
• Specific carrier systems for the uptake of
  ?
• Endothelium is surrounded by ? and
  ?

Answer 8

 The blood-brain barrier consists of specialized capillary endothelial cells that are lined by the basal lamina, astrocytic endfeet, pericytes and microglial cells.

In brain capillaries, passage through intercellular clefts is blocked by tight junctions, and exchange of blood solutes is highly selective.

The blood brain barrier–histological characteristics:

• Few or no fenestrations
• Pinocytosis very uncommon to observe at
  the BBB (pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell membrane)
• tight junctions
• luminal (ventral side) and abluminal side of the
  endothelium (polarized)
• Specific carrier systems for the uptake of
  solutes
• Endothelium is surrounded by pericytes and
  astrocytes

Question 9

Cerebrospinal fluid and blood-brain barrier

The blood-brain barrier–functional characteristics:

• Molecules that are ?, uncharged, ? soluble, and ? to plasma proteins (e.g., O2, CO2, ethanol, nicotine) can easily pass across the ? of the BBB
• Molecules that do not fit this profile (e.g., glucose, some amino acids) are able to pass through the BBB by specific, ? transport mechanisms
• Many antibiotics, anti parasitic drugs, as well as various potentially harmful substances will be ** “ ? ” ** by the BBB (carrier-mediated process!) and will never reach the nervous tissue

Answer 9

Cerebrospinal fluid and blood-brain barrier

The blood-brain barrier–functional characteristics:

• Molecules that are small, uncharged, lipid soluble, and bound to plasma proteins (e.g., O2, CO2, ethanol, nicotine) can easily pass across the capillary endothelium of the BBB
• Molecules that do not fit this profile (e.g., glucose, some amino acids) are able to pass through the BBB by specific, carrier-mediated transport mechanisms
• Many antibiotics, anti parasitic drugs, as well as various potentially harmful substances will be ** “ REPELLED ” ** by the BBB (carrier-mediated process!) and will never reach the nervous tissue

Question 10

Cerebrospinal fluid and blood-brain barrier

Transport systems at the BBB (the most representatives):

Transport systems for glucose (GLUT)
Lactate and ketone bodies (MCT, monocarboxylic acid transporter) Amino acids transporters
OATPs/Oatps (Organic Anion Transporting Polypeptide) OCTs/Octs (Organic Cation Transporters)
OATs/Oats (Organic Anion Transporters)

V common to have MDR1 mutations

** Pgp: MDRs (Multidrug Resistance Protein) ** - ONLY KNOW MDR1 !!! (ignore the rest) - here protein doesn’t function appropriately -> so what happens is if protein carrier isn’t working: if antiparasitic and antibiotic that doesn’t normally go into the brain (e.g. IVERMECTIN) then will pass barrier and then abnormally high amount of drug in brain then we’d say

MRPs (Multidrug Resistance Associated Protein)