Thursday, 3-24-General Neurophysiology (Karius)

Question 1

Describe the 2-stage process of CSF formation:

Answer 1

Step 1: Passive filtration of plasma across the choroidal capillary endothelium
Step 2: Modification of the composition by the choroid plexus: HCO3, Cl, and K concentrations controlled by channels on epithelial cells. Aquaporins also exist

Question 2

Which ions exist in equal (or nearly so) concentrations in both the plasma and the CSF?

Answer 2

• Na
• Cl
• HCO3

Question 3

Which ions/molecules have a greater concentration in the CSF compared to the plasma?

Answer 3

• Mg2+ (KNOW THIS)

- CO2

Question 4

Which ions/compounds exist in greater concentration in the plasma compared to the CSF?

Answer 4

• K+ (KNOW THIS)
• Ca2+
• Protein
• Glucose (KNOW THIS)

Question 5

CSF flows through the ventricular system. However, the flow is one way and the CSF must be ___ at the end

Answer 5

Reabsorbed

Question 6

Absorption of CSF is done by the ___

Answer 6

Arachnoid villi

• Endothelium of sinus and the membrane on the villi have fused
• bulk flow of CSF into venous sinus is primary
• pinocytosis also documented

Question 7

Absorption of CSF is proportional to intracranial pressure. At pressures below ___ mm CSF, no absorption. Normal pressure is about __ mm CSF

Answer 7

68

112

Increased pressure causes damage to neurons

Question 8

During circulation of CSF, from the arachnoid villi, the CSF enters the ___ by bulk flow

Answer 8

Venous sinuses

Question 9

Regarding the BBB, capillaries in the brain have these 2 components that limit exchange:

Answer 9

• Tight junctions between endothelial cells

- Glial endfeet come in close contact with BV

Question 10

Passive diffusion of these substances cross the BBB:

Answer 10

• H2O
• CO2
• O2
• Free steroid hormones

Question 11

What is the major energy source for neurons?

Answer 11

Glucose–> which does NOT cross the BBB readily

Question 12

How does glucose cross the BBB?

Answer 12

GLUT1 transporter–> NOT insulin-dependent

• 55k on capillaries
• 45k on astroglia

Question 13

___ transporter moves ions from the CSF to the blood. Its expression is tied to endothelin 1 and 3

Answer 13

Na/K/2Cl

• Endothelin production tied to a signal from the astrocytes
• May be related to [K+] csf

Question 14

Many drugs do in fact cross the BBB but are moved back to the blood via ___

Answer 14

P-glycoprotein

Question 15

What are functions of the BBB?

Answer 15

• Maintain electrolyte composition –> particularly related to K+, maintenance of Vm
• Protection from toxins
• Prevent escape of NT’s
• Protect composition of CSF

Question 16

There are several places in the brain where we want the brain exposed to the blood. In these regions, the capillaries do not have ___ between endothelial cells

Answer 16

Tight junctions

Question 17

The ___ are neural tissue that is “outside” or not as well protected by the BBB as other neural tissue.

Answer 17

Circumventricular organs

Question 18

What are the 4 regions of circumventricular organs that are not as well protected by the BBB as other neural tissue?

Answer 18

• Posterior pituitary
• Area postrema
• OVLT
• Subfornical organ

Question 19

The ___ is involved in vomiting

Answer 19

Area postrema

Question 20

The __ and __ are both involved in control of body water/thirst/blood volume control (angiotensin)

Answer 20

OVLT and subfornical organ

Question 21

What percentage of CO does cerebral circulation receive?

Answer 21

14% of CO (750 ml/min required)

Question 22

The ___ and __ join to form the circle of willis

Answer 22

2 internal carotids and basilar artery

-There is little mixing of blood from the 2 different sources

Question 23

What is the impact of the non-mixing of blood in the circle of willis?

Answer 23

Disruption of 1 of the inputs produces localized (discrete) areas of ischemia

Question 24

Regarding sympathetic innervation, list the neurotransmitters and receptors involved in cerebral circulation:

Answer 24

NT’s: Norepi and NPY

Receptors: alpha-adrenergics

Question 25

What is the outcome of sympathetic innervation to cerebral cicrulation?

Answer 25

Leads to constriction when systemic CO/BP increases

Question 26

Regarding parasympathetic innervation of cerebral circulation, describe the BVs, list the NTs, and the outcome of parasympathetic innervation:

Answer 26

- Larger BV's - NTs: Ach, VIP, PMH-27 (derived from pre-pro-VIP) - Causes vasodilation

Question 27

What are the NT's involved in sensory innervation of the distal BVs (cerebral circulation)?

Answer 27

- Substance P (dilation) - Neurokinin A (dilation) - CGRP (dilation)

Question 28

Describe the role of sensory innervation of cerebral circulation:

Answer 28

- In the presence of reduced CSF volume, the brain is effectively heavier and simple motion can cause pain of the "torsion" of BV's - The activation of those afferents will also cause vasodilation and increase blood flow (returns total intracranial volume closer to normal?)

Question 29

Cerebral blood flow is under ___ control; O2 consumption dictates where in the brain the blood will go

Answer 29

Local

Question 30

Cerebral blood flow is strongly influence by intracranial pressure: as intracranial pressure goes up, ___ is obstructed leading to reduced arterial flow

Answer 30

Venous outflow

Question 31

Cerebral blood flow is strongly ___ - that is, it is held constant over a wide range of systemic (mean arterial) blood pressures

Answer 31

Autoregulated

Question 32

In the face of high BP (which could damage the BBB), sympathetics in the brain will ___ the vasculature

Answer 32

Vasoconstrict --> Although this will increase the systemic vascular resistance, it protects the capillaries in the brain from damage

Question 33

Regarding cerebral circulation and the effects on mean arterial pressure, a decrease in brain perfusion will activate the ___ and increase systemic BP-sometimes drastically

Answer 33

Vasomotor centers

Question 34

What can increase the intracranial pressure?

Answer 34

- hydrocephalus of any variety - edema - bleeding within the skull

Question 35

If blood flow is compromised, the brain will drive systemic BP __ to force blood to the brain

Answer 35

UP Consequence: systemic BP can be driven to very high levels in order to perfuse the brain

Question 36

Most of the CSF (50-70%) is made by the specialized tissue of the ___

Answer 36

Choroid plexus -The remaining CSF made by the tissue that lines the ventricles and blood vessels

Question 37

Where is the choroid plexus located?

Answer 37

Floor of the lateral, 3rd, and 4th ventricles

Question 38

Compare the CSF pH to the plasma pH (normally):

Answer 38

CSF pH=7.33 | Plasma pH=7.4

Question 39

What is the pathway of CSF?

Answer 39

From ventricle --> through foramens of Magendie and Luschka (2 different paths) --> to subarachnoid space --> absorption of CSF into blood (absorption in arachnoide villi)

Question 40

Hydrocephalus can be caused by:

Answer 40

- Decreased absorptive capacity of the arachnoid villi (external hydrocephalus or communicating hydrocephalus) - Blockage of either foramen or somewhere else in the ventricular system (internal hydrocephalus or noncommunicating)

Question 41

The Na/K/2Cl transporter moves these ions from the CSF to the blood and is stimulated by ___

Answer 41

Endothelin 1 and Endothelin 3 Likely helps keep [CSF] of K+ low

Question 42

This circumventricular organ is at the caudal portion of the 4th ventricle-the chemotactic trigger zone that initiates vomiting from blood-borne chemicals

Answer 42

Area postrema

Question 43

Describe the endothelial cells and capillaries of the circumventricular organs?

Answer 43

Endothelial cells do NOT have tight junctions between them | Capillaries are fenestrated

Question 44

Regarding innervation of cerebral vasculature, post-ganglionic sympathetic fibers have cell bodies in the ___ ganglia

Answer 44

Superior cervical

Question 45

___ nerve fibers are found on smaller arteries, are sensitive to vasodilation and torsion of blood vessels, and contain substance P, neurokinin A, and CGRP

Answer 45

Afferent

Question 46

As intracranial pressure increases, blood flow is ___ due to compression of the blood vessels

Answer 46

Reduced

Question 47

As systemic BP increases, the sympathetic innervation of the cerebral vasculature becomes ___

Answer 47

MORE active --> releases more norepi --> binds to alpha-adrenergic receptors --> causes VASOCONSTRICTION of cerebral vasculature EFFECT=PROTECT THE BBB

Question 48

One sign of an increase in intracranial pressure (e.g., hemorrhage) is an increase in ___

Answer 48

Systemic BP If blood flow to the brain is severely compromised, the systemic BP can go incredibly high

Question 49

___ is an enlargement of the ventricles (particularly lateral) in the brain. It is frequently a result of hydrocephalus of some form but there is a congenital form which is not related to increased intracranial pressure

Answer 49

Ventriculomegaly

Question 50

___ is an accumulation of excess CSF and results from a mismatch of production (which is constant) and reabsorption (which changes depending on CSF pressure)

Answer 50

Hydrocephalus

Question 51

What type of diet can be beneficial to children with a BBB GLUT-1 deficiency?

Answer 51

Ketogenic--> ketone bodies get across BBB through MCT-1 and used for energy for neurons