Lecture 6 - Blood-Brain Barrier and CSF Flashcards
what is the blood brain barrier? (BBB)
- brain and the spinal cord are protected from the general circulation of blood in the body
- The extracellular fluid in the neuronal environment (brain and spinal cord) are carefully regulated through Blood-Brain Barrier (BBB)
why is it important to regulate the ionic composition of the extracellular fluid around the neuron (2)
review from previous lessons
how do we achieve this regulation?
we learned that
* The ionic composition of the extracellular fluid around the neuron must be carefully controlled:
- cannot change the excitability of the membrane (ex. with KCl injection –> decreased K+ concentration gradient –> depolarization –> inactivation of the Na+ channel –> no more AP produced)
- cannot have neurotransmitters floating around for no reason (this will confuse the system)
- achieve regulation with blood brain barrier BBB
How can the BBB be thought of as a 2-fold entity
aka what is the blood separated from (2)
- the blood (capillaries): sodium, potassium and protein
this is separated from: - 1st barrier: interstitial fluid (fluid bathing neurons): sodium, potassium and protein
- 2nd barrier: Cerebral Spinal Fluid CSF ventricles (fluid in ventricles in the brain)
Note there is 2 barriers even though there are 3 compartments because the barrier between the interstitial fluid and the CSF ventricles is a “non-barrier”
- free diffusion of chemicals
- chemical composition is almost identical
how is the BBB sometimes harmful and can cause some diseases/muscle cramps (2)
parkinson’s disease
- problems w/ lack of dopamine –> muscle stiffness
- normally you would try to inject dopamine to help
- but BBB prevents dopamine injected in blood veins to reach the brain and thus wont work well
- instead gives them al-dopa
- precursor of dopamine that does cross the BBB and gets converted to dopamine once in the brain
MSG
- MSG is in a lot of foods
- we get thirsty and sometimes get a stiff neck after consuming
- MSG cannot cross barrier and access brain but it can activate glutamate receptors outside the brain in the peripheral nervous system
what are two specific areas that lack the BBB
- Most of the brain is protected by BBB, but it is not continuous
- At some places it is essential for neurons to communicate freely with the blood
stream (e.g. hypothalamus) - The pituitary gland (releases hormones) and is directly connected to the hypothalamus > thus, BBB is purposely broken to allow release of hormones
- In ‘Circumventricular organs’ (around 3rd ventricle) the BBB is broken so neurons can sense specific chemical concentration
- Generally, BBB is broken in areas that interact with endocrine system or in the central nervous system to sense metabolites in plasma in the general circulation
what is the brain physically encased by for protection?
furthermore, what is the brain cushioned by for protection - cranial and spinal meninges (3)?
- the skull or the backbone is the first line of defense for the brain
- brain and spinal cord are cushioned by many layers of matter for protection:
1. Dura mater - very tough membrane sac encloses the brain and spinal cord
2. arachnoid membrane - much more delicate tissue
3. pia mater (lies right on top of the brain - closest; tethered to arachnoid by arachnoid ‘trabeculae’
what is subarachnoid space? what does this mean about the position of the brain in our body?
- there is space between the arachnoid membrane and the pia mater = subarachnoid space
- In the subarachnoid space, we have blood vessels –> capillaries to the brain tissue –> BBB, in between the capillaries and the brain tissue
- this subarachnoid space is filled with CSF (cerebral spinal fluid)
- thus, the brain is literally floating in fluid to protect from mechanical stress –> cushion
what is reticular formation and why do we not want to mess with it?
- collection of loose nerve cells that connects the brain to the spinal cord for manifestation of behaviour
- punching someone hard in the jaw may shake the reticular formation –> lead to someone passing out
how do we prevent the blood from mixing with the interstitial fluid? ie. how does the BBB work due to its endothelial lining?
- the endothelial cells have whats called tight junctions
- the endothelial lining of the blood vessels, mostly contain large gaps (fenestrations), through which molecules can pass
- In Brain, endothelial cells are tightly bound leaving no gaps > this constitutes the BBB (everything has to be transported)
what are brain ventricles?
where is the lateral ventricle?
where is the third ventricle and what channel does it use to communicate with the 4th ventricle?
how is the 4th ventricle connected to the spinal cord?
- The ventricles are cavities deep inside the brain – all ventricles are filled with CSF
- We have a large curving Lateral Ventricle (LV) inside each cerebral hemisphere, a paired structure across the midline
- The LV is connected to the 3rd Ventricle, right in the middle, deep in the brain under the cerebral hemisphere
- The 3rd Ventricle communicates via a channel called “Aqueduct of Sylvius” to the 4th Ventricle
- From the 4th Ventricle, we have a canal, “Central Canal” which goes in the middle of the spinal cord
- there is a continuous connection between all ventricles and the spinal cord
what is the movement of CSF like in the ventricles?
- CSF produced in the choroid plexus which is located in the ventricles (LV, 3, 4)
- travels to the central canal
- CSF then moves to outer parts of the brain (subarachnoid space) and finally exits at the top of the brain into large venous sinus (on the midline) – essentially exits back into the general circulation
- therefore all the CSF eventually drains into either venous sinus or veins (general circulation) somewhere along the line
- About 1⁄2 CSF drains through ‘Arachnoid villi’ into the venous system
note circulation of CSF occurs without a pump, unlike the heart
how does the shape of the arachnoid villi contribute to the CSF being able to drain back into the general circulation/venous system?
Arachnoid Villi is an out pouching of the arachnoid tissue, sticks out through the dura matter into the venous sinus –> CSF drains into the venous system
CSF Pathway
- Ventricles are filled with CSF, which is the bathing medium of brain (highly regulated ionic content, few macromolecules)
- CSF is produced from blood/plasma by ‘choroid plexus’, which lines the ventricles (LV, 3rd, 4th, all have choroid plexus producing CSF)
- All the ventricles are filled with CSF (including the subarachnoid space, there is communication between the ventricles and the subarachnoid space) and eventually drains into the venous system
in all, CSF made in plasma that lines the ventricles and eventually drains back into blood circulation by the venous system
- there is circulation of CSF –> made and drained continuously
- this cycle allows for a cleansing mechanism
does choroid plexus make all the CSF?
what is choroid plexus made up of and connected by?
how much CSF does choroid plexus produce per day?
- Choroid Plexus produces most of CSF (but not all, some are produced in the capillaries inside the brain)
- Made up of epithelial cells connected by tight junctions
- Choroid Plexus produces CSF continuously (550 ml/day) to circulate –> cleansing
mechanism - Choroid Plexus is a dense network of capillaries ballooning out into the ventricular wall with tight junction so that everything has to be transported
RECAP:
- where is CSF produced
- where does CSF fill (2)
NEW:
- what is the osmolarity and [Na+] of CSF similar to?
- how is the [K+], [Ca2+] and [Mg2+] in CSF different than blood?
- what is the total volume of CSF in a person –> cranial and spinal?
- what does the CSF in the subarachnoid space serve as?
- CSF is produced by ‘Choroid Plexus’ in ventricles
- CSF fills the ventricles and the subarachnoid space
- CSF has same osmolarity and [Na+] as blood
- Greatly reduced [K+], [Ca2+] and [Mg2+]
- Total volume on an average person is 215ml
- Cranial CSF is 140ml (25ml in ventricles, 115ml in subarachnoid space) and the spinal CSF is 75ml
- Thus, most of the CSF is in the subarachnoid space, serving as ‘cushion’
