Introduction

• • What do we mean by CNS micro_environment?

• • Because the brain is very protected organ,
• • Everything that surround neurons = CNS micro_environment
• • To make sure the neuron can work propably.
• • The neuron can have a good excitabelity threshold.
• • Neurons need to be protected from the changes in the periphery.
• • Neurons not influenced by perephral hormons, metabolites, neutrients, etc.
• • Huge amount of blood continously flowing to the brain.
• • If you block blood supply to the brain = loss of consiosness very fast.
• • Rapid depletion of ATP in the brain if there is no blood supply.
• • Introduce brain deterioration and perminant brain damage.
 Introduction
• • The brain is very sensitive to the metabolic changes.
• • The brain need to be protected from the changes in
the periphery.

• •CNS ENERGY CONSUMPTION:

• • To maintain the ion-gradients

• •(NA+ , K + , ATPases)
20 20
• • To make sure nuerons can have correct excitabelity so
 Overview
• • Introduction _ What is the CNS micro_environment?
• • Introduction _ Importance of a constant micro_environment
• • Blood supply
• • Cerebrospinal Fluid (CSF) & the blood _ CSF barrier
• • Brain extracellular fluid (BECF) & The Blood _ Brain Barrier
• • Astrocytes
 Introduction

• • We need a protected, stable Microinvironment of CNS.

• • By continous supply of energy.
• • The level of concentration of Ions need to be maintained very strictly.
• • To preserve a good excitation threshold of neurons.
• • Other substane (amino acids) used by neurons to synthesis.
• • Neurotransmetter need to be kept in a very controled concentration.
• • Other signalling molecules (hormones, growth factors, cytokines, etc)
• • Some of them have to reach the brain and others NEVER.
 Introduction Ktafterexercisebemusclecontraction
to
stopexit
abilityofneurone

• • Blood levels of ions and neutrients are not constant and contiously changed.
• • E.g. free K + level circulating in the blood,
• • Medically increase after exercise because of muscle contractions.
stop
• • It lead to halt the excitability of neurons in the brain.
protected
• •Therefore, the blood is sealded from the brain Microinvironment.
• • Amino acid concentration after protien rich meal.
• • Interfer with neurotransmetter synthesis in the brain.
• • Therefore, a lot of barriers are needed in the brain. Why?
• • To devide the CSF from the blood level bychoroidPlexus
• • Also to devide the brain extra cellular fluid from the blood levels.byBBB
 CNS Micro-Environment
• • Relationship between the blood flow and (CSF & brain extra cellular fluid).

• • FLUIDS:
2 3
I
• • Blood, Cerebrospinal fluid (CSF) and brain extra cellular fluid (BECF).

• • BARRIERS:
• • Blood – CSF = Choroid Plexus (Produce CSF).
• • Blood – BECF = Blood Brain Barrier.

• • CELLS:
• • Glia cells and Neurons.
 Overview
• • Introduction _ What is the CNS micro_environment?
• • Introduction _ Importance of a constant micro_environment
• • Blood supply
• • Cerebrospinal Fluid (CSF) & the blood _ CSF barrier
• • Brain extracellular fluid (BECF) & The Blood _ Brain Barrier
• • Astrocytes
 Blood - Arteries

• • Four main enrances of the blood

into the brain

• •Two of them in the back of the brain

close to the Vertebrae:

Vertebral arteries

• •The other two are Infront:

Internal carotid artery

 Blood - Arteries
• • There is a connection between these
arteries which form a circle:
Circle of Willis

• •To make sure that we have always

blood supply to the brain even if
there is an obstruction or a lesion
in the other part of this circle.

• •Then we still have blood supply

coming from the other root.
 Overview
• • Introduction _ What is the CNS micro_environment?
• • Introduction _ Importance of a constant micro_environment
• • Blood supply
• • Cerebrospinal Fluid (CSF) & the blood _ CSF barrier
• • Brain extracellular fluid (BECF) & The Blood _ Brain Barrier
• • Astrocytes
 Cerebrospinal Fluid (CSF)
• • Coronal Section:

• • Lateral ventricles
PrancebychoroidPlexus
• • There is a kind of good equilibrium between the

fluid in the brain tissues and the CSF in the ventricles.

• • But there is a specific cell lining in the ventricles

by ependymal cells (glia cells) .

• •CSF is produced by choroid plexus & then floating into

the ventricles .

• • And from the ventricles to the subarachnoid space.

• • And from the subarachnoid space the CSF choroidplexus

can be expelled into the venous system. ventricles

• • In total we have 150 ml of the CSF. subarachnoid

venous
t
system lateralv
• • 120 ml floating in the subarachnoid space

8
t
• jgp
• 30 ml floating in the ventricles. 3rdv
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centralcana
spare
Cerebrospinal Fluid (CSF)
• • In the subarachnoid
space the CSF
is continuously
surroundings the brain

• •Direct contact why toabsorpin

tovenussystem
between the blood
vessels and the
subarachnoid space
 Cerebrospinal Fluid (CSF)

• • The CSF exit from the fourth

ventricle to the subarachnoid
space.

• • Then the CSF expelled from

the subarachnoid space into
the venous sinus.
Cerebrospinal Fluid (CSF)
• • Graphic presentation
of different ventricular
system.

• • Presenting the opening:

in which the CSF fluid
flow from the fourth
ventricle to the
subarachnoid space.
 Cerebrospinal Fluid (CSF)
• • physical Function:
• • A. Shock absorbance to protect
the brain.

While we are walking, if we don’t have CSF

surroundings the brain in the subarachnoid
space. We will continously have a headach.

E.g. recovering from alcohol intoxication,

rapidly fluid depletion that lead to water
extraction from CSF. Lead to experience
headach feeling.
Cerebrospinal Fluid (CSF)
• • physical Function:
• • B. Reduce weight. To make sure the
pressure around the brain is equally distributed and
this make an equal pressure that maintain the brain
in it’s place.

• • C. Waste management a lot of

metabolites produced in the brain tissues can be
secreted into the CSF
• • The total volum of CSF production is around 500 ml.

• • While we have 120 ml in the subarachnoid

spaceand 30 ml in the vintricls.
• • Means that three times every day we got a
complet refreshment of the CSF.
• • So, it’s an ideal place to get rid of toxic metabolites
into the CSF.
 CSF -Composition
• • Electrolites and other substances:

Low
• • Point to notice is that:

conccentration of K+ ,
amino acids and Protiens
in the CSF.
• • Active system is needed

to control these level of of

K+ , amino acids and Protiens in the plasma blood
vessels and not entring the CSF.
42 29
26 0.7
7 0.03
 CSF - Production
ÉÉÉ
• • Blood vessels in the choroid plexus:
• • Production of CSF is Two steps process:
i É
• • A. Step 1: Ultrafiltration: in which cells and big
protiens can not pass (the fenestra) in between the blood
vessels and the epithelial layer of the choroid plexus.
14
• • Step 2: Active transport mechanisms: to
make suer that the right concentartion of the electrolites
(e.g K+), amino acids and other neutrients (e.g glucose) are
entring the CSF.

• • Passive diffusion of lipid soluble molecules,

gases and H2O.

• • B. Iso osmotic secretion: means that the net

flow of ions in both direction stay equal. (e.g. NaCl, H2O)
form blood to CSF and vice versa.
 CSF - Production
• • Inthe choroid epithelial layer there are a lot of pumps and
channels and transportes to maintain the right
concentration:

• • K+ need to be kept very low in the CSF:

• • OHcarbonate
Carbon anhydrase: splet CO2 to Hydrogen
cos
or bicarbonate. In which cells and big protiens can not pass (the
fenestra) in between the blood vessels and the epithelial layer of the
choroid plexus.

• Carbon anhydrase: lead to block

• Block of
CSF Production.
• • Iso-osmotic secretion= net transport of

NaCl + NaHCO3 + water.

• • Ion homeostasis
K+ , H+/HCO3- , Mg2+ , Ca2+soluble molecules, gases and H2O.
 CSF - Absorbtion nottheproduction

• • CSF excretion to Venous

sagital sinus occur:
• • Through transcytosis process: by
the pressure of the fluid in the CSF in the subarachnoid
pressuredependent
space and then transported to the Venous sinus.

• One-way valve
•

mechanism

• • Fluid containing vacuoli

CSF - HYDROCEPHALUS

• •when ther is over production

of CSF that lead to
enlargment of the vintricles.

• •The other case is another way

around in which there is
shrinkage of the vintricles
because thers no enough CSF
production from choroid plexus is:
Ventriculoatrial (VA), Ventriculopleural (VPl) &
Ventriculoperitoneal Shunts
 Overview
• • Introduction _ What is the CNS micro_environment?
• • Introduction _ Importance of a constant micro_environment
• • Blood supply
• • Cerebrospinal Fluid (CSF) & the blood _ CSF barrier
• • Brain extracellular fluid (BECF) & The Blood _ Brain Barrier
• • Astrocytes
(BECF) - Location
• • Electron microscopic picture:

• • Tiny space between brain cell = 20nm.

• •Around 20% of the total brain volum.

way to decrease the intracranial
pressure

• •Place for metabolites transportation,

neutrients & electrolites.
• •Reduce diffusion Rat. To Prevent the
over excitability of the neuron.
 (BECF) - Function
• • Route for metabolites:
–Anabolites (O2, glucose, amino
acids)
–Catabolites (Co2, catabolites of
neurotransmitters)

Paracrine
• •

communication:
–Neurotransmitters
–Trophic factors
(BECF) – Composition
≈ more or less the same of
• •

CSF :

Free exchange between CSF

• •

and BECF via :

– ependymal cells (ventricles)
– pial-glial membrane (glia limitans):
between BECF and subarachnoid
CSF
 The Blood _ Brain Barrier
• • Astrocytes:
Help to maintain homeostasis.
Extend via pia mater to form pial-glial
membrane. C
• • When pia mater terminated:
– Astrocytes surroundings the small
capillaries to seald blood from brain
tissues Frate
– To maintain the uptake the electrolites,
neutrients, and get rid of the over
activity of Ca++ & neurotransmitter
metabolites
 (BECF)– Sequestration/absorption
• • The Blood _ Brain Barrier consists of three parts:
• -Endothelial cells: connected through “tight junctions”(zona occludens).

i
• -Basal membrane (around endothelial cells).

• -Astrocyte endfeet.

• • The Blood _ Brain Barrier is found in all cappillaries that run through the brain.
The Blood _ Brain Barrier (BBB) - Location
Sha i posput
• • All vertebrates: 2 subsornicalougan
3 subcommisural
y pinealgian
5 mediahemenance
• • No BBB in: o areapostrema

– Choroid plexus
– Group of structures surroundins the
ventricles called circumventricular
organs which is typical (neuroendocrine
control system). It works as sensor
situation to sense concentration of
gases, electrolites, hormons, nuetrients
into the blood to give the brain to
change homeostasis. Happen at the
area of hypothalamus, pituitary and
OVLT.
 The Blood _ Brain Barrier (BBB) - Function
• •Protection of CNS (Neurons)
from
change
fluctioation in plasma
concentration.
• • Free crossing of: Passivedissution
– Water
– Uncharged and lipophilic molecules.

• •Active transport system for

other molecules (e.g. K+) to
maintain the right acid balance.
The Blood _ Brain Barrier (BBB) - Transporters
 Overview
• • Introduction _ What is the CNS micro_environment?
• • Introduction _ Importance of a constant micro_environment
• • Blood supply
• • Cerebrospinal Fluid (CSF) & the blood _ CSF barrier
• • Brain extracellular fluid (BECF) & The Blood _ Brain Barrier
• • Astrocytes
 Glia cells - Astrocytes
• • Proliferating cells (lifelong)

• • ✓½ brain volume•
• • ✓10 glia for 1 neuron
• • White, gray matter, in myline and in cortical area.
• • in White matter called Fibrous Astrocyte and it work
to maintain structures.
• • in gray matter called Protoplasmic Astrocyte
o
• • Radial glia cells (neural development),

o o
glia of Muller (retina), glia of Bergmann (cerebellum).
fibrous
protoplasmic
muller
Bergmann
 Astrocytes - Functions
• • Historically: “Brain glue” (Keeping the neurons together)

• • Now: Actively take part in neurotransmisison signaling,

and in development

main direct Glucosegodirectlytothe

brain
•  Energy supply
y Glucosegoto asterocytethantobrain
•  maintaining ion concentartion e.g. [K+]0
•  Regulate Neurotransmitter synthesis and breakdown
Astrocytes – Energy supply
Astrocytes – K+ homeostasis
Astrocytes – K+ homeostasis
Astrocytes –Neurotransmitter homeostasis
The End
Questions?