Lecture 14: General Neurophysiology Flashcards
What is the two-stage process in the formation of CSF; conncentrations of what ions are controlled and how does water cross?
Step 1: Passive filtration of serum
Step 2: HCO3, Cl-, and K+ concentrations are controlled by channels on epithelial cells. Aquaporin 1 allows H2O to cross
How does the production of CSF change over a wide range of intracranial pressures?
Production of CSF is constant, regardless of ICP
What is found in equal concentrations between the CSF and plasma?
HCO3-
What is found in higher concentration in the CSF then in plasma?
- Mg
- Cl-
- CO2
What is found in higher concentration in the plasma than in the CSF?
- K+
- Ca2+
- Protein
- Glucose
Absoprtion of CSF is proportional to ICP; at what pressure is there no absorption?
Pressures below 68 mm CSF
Capillaries in brain have 2 components that limit exhange, what are they?
- Tight junctions between endothelial cells
- Glial endfeet come in close contact w/ BV
Which molecules are able to passively diffuse across the BBB; what channel for water?
- H2O via AQP-4
- CO2
- O2
- Free steroid hormones (not protein bound)
What is the major energy source for neurons and how are they able to acquire it; does this process depend on insulin?
- Glucose
- Glut 1 transporter to cross BBB
- Two forms: 55K on capillaries and 45K on astroglia
- NOT insulin dependent!
- Neurons use Glut-3 to move glucose in
What is the purpose of the Na/K/2Cl transporter on the BBB; expression of this transporter is tied to?
- Move all of these ions from CSF —> Blood
- When thinking hard, the [K+] of your CSF will increase and needs to be removed to maintain the RMP of the neurons
- Expression tied to endothelin 1 and 3
- ET production tied to signal from astrocytes
- May be related to [K+]CSF
Many drugs do cross the BBB but many of which are quickly moved back to blood by what?
P-glycoprotein
What are the 3 major functions of the BBB?
- Maintain electrolyte composition, particularly K+ and Vm (membrane potential)
- Protection from toxins
- Prevent escape of NTs
In the nueronal areas where we don’t want a BBB, what strucutral piece is missing?
Tight junctions
What is the name of the organs that are neural tissue not protected by the BBB; how many regions?
- Circumventricular organs
- There are 4 regions
What are the 4 circumventricular areas that lack BBB
- Posterior Pituitary: releases hormones into blood
- Area Postrema: trigger zone for vomiting
- Organum Vasculosum of the lamina terminalis (OVLT): involved in control of body water/thirst/blood volume
- Subfornical organ: involved in control of body water/thirst/blood volume
What are the NT’s, receptor, and function of the sympathetic innervation of cerebral circulation?
- NT’s: Norepi and NPY
- Receptor: α-adrenergic
- Function: leads to constriction when systemic cardiac output/BP increases
What are the parasympathetic NT’s and function for cerebral circulation?
- ACh, VIP, PHM-27 (derived from pre-pro-VIP)
- Cause vasodilation
Which vessels of the cerebral circulation have sensory innervation?
Distal blood vessels
What 3 NT’s are released at the blood vessels in cerebral circulation and cause vasodilation?
- Substance P
- Neurokinin A
- CGRP
The sensory fibers of the vasculature of cerebral circulation render the vessels extremely sensitive to what?
Torsion/manipulation - lead to pain
What is the role of sensory innervation of the cerebral circulation in the presence of reduced CSF volume?
- Brain is effectively heavier w/ reduced CSF and simple motion can cause pain due to torsion of the BV’s
- Causes activation of the afferent fibers, which will cause vasodilation and increase blood flow
Cerebral blood flow is under local control; what dictates where in brain blood will go?
Oxgen consumption
Cerebral blood flow is under what kind of regulation?
- Auto-regulation
- Held constant over a wide range of system (mean arterial) BP’s
In the face of high BP (>140 mmHg) the auto-regulation mechanisms of the brain will not be able to maintain constant blood flow, what system will come into play?
- Sympathetics in brain will VASOCONSTRICT (Norepi and NPY) the vasculature
- This will increase the systemic vascular resistance, but it protects the capillaries in the brain and the blood brain barrier from damage
- Damage may occur within systemic vasculature/organs, but at the end of the day the brain takes precedent
Cerebral blood flow is strongly influenced by ICP, what occurs as the ICP goes up?
- Venous outflow is obstructed
- Leading to reduced arterial flow
As ICP increases, venous outflow is obstructed, and arterial flow/perfusion of the brain will be decreased, what does this lead to?
- Activation of vasomotor centers and increase systemic BP - sometimes DRASTICALLY (>300 mmHg)
- Brain will do everything it takes to get blood perfusion
Which aquaporin is most important in controlling brain-water balance?
AQP4
