CNS homeostasis Flashcards
What is in the extracellular space of the brain? (2)
- Extracellular matrix
- Brain extracellular fluid (BECF)
How could BECF composition be affected by increased neuronal activity?
- Increased K+ concentration
- Changes in Ca2+
- Changes in glucose, CO2, O2 conc.
- Increased neurotransmitter concentrations
How could a change in BECF composition change neuronal activity?
- Increased K+ concentration in BECF could bring the resting potential closer to the threshold for action potential
- Increased neurotransmitter conc. could caused unspecific receptor activation and unspecific neuronal activity
How is the neuronal microenvironment regulated? (4)
- Blood brain barrier
- Cerebrospinal fluid (CSF) in the ventricular system
- Neurons
- Glial cells
How was the blood brain barrier discovered?
- Intravenous dyes injected into mice
- Soft tissues were stained
- No staining in the brain
What is the function of the blood brain barrier?
- To protect neurons from fluctuations in concentrations in substances in the blood
- E.g. increased amino acids in the blood after a meal could stimulate neurons in the brain without regulation, ions after exercise, hormones, toxins etc.
How is the blood brain barrier maintained? (3)
- Tight junctions between endothelial cells eliminate the paracellular route
- Thick basement membrane
- Astrocytic endfeet (from glial cells - astrocytes)
How do necessary molecules get through the blood brain barrier?
- Facilitated transport
- Exchangers
- Co-transporters
Which organelle is needed in increased numbers in the blood brain barrier?
Mitochondria for active transport
Which molecules can pass easily through the blood brain barrier?
- Small, uncharged, lipid soluble
- E.g. O2, CO2, nicotine, heroin, caffeine
Which drugs can easily pass through the blood brain barrier? (3)
- Nicotine
- Heroin
- Caffeine
What are the 2 main leaky regions of the blood brain barrier?
- Choroid plexuses (ventricular system)
- Circumventricular organs
What are ependymal cells?
Ciliated-epithelial glial cells
Why do we have leaky areas of the blood brain barrier? (3)
- Hormone release from the hypothalamus and pituitary gland
- Osmoreceptors
- Temperature control centres
What is the ventricular system?
A set of 4 connected cavities in the brain filled with cerebrospinal fluid
What is the purpose of cerebrospinal fluid?
- Provides physical protection to the brain against the skull, makes it effectively “lighter”
- Maintains appropriate levels of ions in then brain by adding/removing waste products
What is the central canal?
Thin tube which is continuous with the fourth ventricle and goes down the spinal chord
What are foramens?
Gaps which allow the cerebrospinal fluid out of the central ventricles and around the outside of the brain
What is the superior sagittal sinus?
Point where cerebrospinal fluid enters the venous system
Where is cerebrospinal fluid made?
From the choroid plexuses
What is the choroid plexus?
Secretory tissue which makes cerebrospinal fluid
How much cerebrospinal fluid is secreted each day?
500 ml per day
Are ependymal cells leaky or do they have tight junctions?
Leaky
What separates the CSF in the ventricles from the brain tissue?
Epithelium of ependymal cells
Is the choroidal epithelium leaky or does it have tight junctions?
Tight junctions
How is cerebrospinal fluid secreted from the choroid plexuses?
- Plasma from (normal leaky) capillaries inside the choroid plexus is filtered
- Substances are selectively absorbed into the CSF in the ventricles across the choroidal epithelium (tight junctions)
- Substances can then move freely between the CSF and the brain tissue across leaky ependymal cells
What are the 2 main differences between the composition of the CSF and plasma?
- CSF has lower K+ than plasma
- CSF has lower amino acid/protein concentrations than plasma
What are the meninges?
3 membranes surrounding the brain and spinal chord
What are the 3 types of meninges?
- Pia mater
- Arachnoid mater
- Dura mater
What are the leptomeninges?
- Pia mater
- Arachnoid mater
What is the pia mater? (2)
- The innermost layer of the meninges which adheres to the surface of the brain and spinal chord
- Very permeable so allows movement between the surrounding CSF and the brain extracellular fluid
What is the arachnoid mater? (2)
- Second layer of the meninges, separated from the pia mater by the CSF
- Has tight junctions so less permeable than the pia mater
What is the subarachnoid space?
Space in between the pia mater and the arachnoid mater filled with cerebrospinal fluid
What are arachnoid granulations?
Protrusions of the arachnoid mater through the dura mater into the superior sagittal sinus through which CSF can enter the venous circulation
What is the dura mater? (2)
- Toughest of the meninges
- Splits into 2 layers: one follows the gyri and sulci of the brain, other layer is an outer layer
What is a gyrus?
Outward bump of the cerebral cortex
What is a sulcus?
Inward bump of the cerebral cortex
What are the 2 types of evaginations of the arachnoid membrane?
- Arachnoid granulations
- Arachnoid villi
What are the 2 types of evaginations of the arachnoid membrane?
- Arachnoid granulations
- Arachnoid villi
How big are arachnoid granulations?
Up to 1cm
What is the function of arachnoid evaginations?
Project through the dura mater into the sinus space to allow CSF to re-enter venous circulation
How does CSF enter venous circulation?
- Rise in pressure of the CSF due to constant production from choroid plexuses causes absorption of CSF into arachnoid projection cells
- CSF taken up in membrane vesicles, fuses with basolateral side of the cell and CSF enters the sagittal superior sinus
Where in the brain does exchange occur between the CSF and BECF? (2)
- From ventricles across ependymal cells
- From subarachnoid space across the Pia mater
Why can substances move across the Pia mater?
Doesn’t have tight junctions
Which substances are transported from the CSF to the BECF? (3)
- Macronutrients e.g. glucose
- Micronutrients e.g. vitamins
- Ions e.g. HCO3-
Why is HCO3- needed in the BECF?
To prevent acidification of the brain
Which substances are transported from the BECF to the CSF? (2)
- Metabolic waste e.g. CO2
- Neurotransmitters and their breakdown products
What is hydrocephalus?
A blockage in the ventricular system which means the CSF can’t drain so leads to a build-up of fluid
What condition arises when the CSF can’t drain properly?
Hydrocephalus
What does hydrocephalus cause?
- Increased cranial pressure
- Cell death in the brain
- Loss of brainstem reflexes (regulation of heart rate etc. in the brain stem)
What are astrocytes?
Specialised glial cells
Which transporter takes glutamate back up into the presynaptic terminal?
EAAT3
What is the function of EAAT3?
Transporter which takes glutamate back up into the presynaptic terminal
Which transporters take up glutamate into astrocytes? (2)
EAAT1 and EAAT2
What is the function of EAAT1 and EAAT2?
Transporters which take glutamate up into astrocytes
What do astrocytes do with glutamate they have taken up?
- Break it into glutamine
- Recycle it into the presynaptic terminal
How can neurons and astrocytes regulate levels of neurotransmitter in the BECF?
Take up neurotransmitter into presynaptic terminal/astrocyte and recycle it to stop neurotransmission
How can neurons and astrocytes regulate levels of K+ in the BECF?
Na+/K+ ATPases transport K+ into cells and Na+ out of cells which decreases extracellular K+
How do increases in extracellular K+ affect astrocytes?
- Increased intracellular K+ due to more uptake
- Causes increased glucose metabolism
- Causes increased activity of Na+/K+ ATPase to take up more K+
Why do neurons have a resting membrane potential of -65mV but glia have a resting membrane potential of -85mV?
- Neuronal membranes are more permeable to Na+ than astrocytic membranes therefore more positive resting potential
- Astrocytic membrane have a higher K+ selectivity (more K+ than Na+)
Why are astrocytes more sensitive to changes in extracellular K+ than neurons?
Astrocytes have higher K+ selectivity than neurons
What is an astrocytic syncytium?
Where adjacent astrocytes are joined via gap junctions
What do astrocytes do when they have increased intracellular K+?
K+ is distributed through the astrocytic syncytium via gap junctions to areas with lower activity/lower K+ concentration
What are gap junctions made of?
Individual connexins join to make a connexon which forms a pore
What is neurovascular coupling?
Coupling of astrocytes to the vascular system
What does increased neuron firing rate cause in astrocytes?
Increased intracellular Ca2+ in astrocytes
How is neurovascular coupling beneficial to neurons?
- Increased neuronal firing rate causes increased intracellular calcium in astrocytes
- Leads to the release of vasoactive substances from the astrocyte
- Can cause blood vessel dilation which increases blood supply to that area
What do MRIs show?
3D structural images of the brain (not activity)
How can brain activity be detected?
- Changes in blood flow to different areas of the brain
- Active neurons need more glucose and oxygen
What are the 2 techniques used to image brain activity by detecting changes in blood flow?
- Positron emission tomography (PET)
- Functional magnetic resonance imaging (fMRI)
How does positron emission topography (PET) work?
Exploits glucose use in the brain
How does functional magnetic resonance imaging (fMRI) work?
Exploits oxygen use
