Lecture 2: Cerebral Vasculature and Brain Homeostasis (Karius)

Question 1

How does O₂ affect blood flow to the brain?

Answer 1

It largely stays the same in response to increasing levels of O2, except at the extremes.

Too low of O2 will cause blood flow to the brain to dramatically increase.

Too high of O2 will cause blood flow to the brain to decrease.

Question 2

How does the parasympathetic nervous system affect blood flow to the brain, and what neurotransmitters are used by it?

Answer 2

Parasympathetics will cause vasodilation when blood pressure is low to increase the portion of the blood reaching the brain via acetylcholine, vasoactive intestinal peptide, calcitonin gene related peptide, and substance P.

Question 3

How might a decrease in CSF cause an increase in blood flow to the brain?

Answer 3

Cerebral circulation is highly sensitive to pain in response to torsion. A decrease in CSF makes the brain less bouyant. This can cause torsion on blood vessels which leads to pain. This in turn causes an increase in blood flow to the brain, potentially to increase CSF?

Substance P and CGRP are in charge of this signaling.

Question 4

What is the blood brain barrier highly permeable to, slightly permeable to, and basically not permeable to?

Answer 4

• Highly permeable:
  
  • CO2
  • O2
  • Lipid soluble substances (like unbound steroid hormones)
• Slightly permeable:
  
  • Na+
  • Cl-
  • K+
• Basically not, but still kind of permeable:
  
  • Plasma proteins
  • Non-lipid-soluble organic molecules.

Question 5

What are the cellular components of the blood brain barrier?

Answer 5

• Pericytes
  
  • Can regulate passage across the blood brain barrier based upon their level of contraction around the fenestra of the capillaries.
• Astrocytes
  
  • Have foot processes that block the fenestra.
• Endothelial cells

Question 6

How does an increase in intracranial pressure affect cerebral blood flow?

Answer 6

An increase in intracranial pressure causes the veins in the cerebrum to become compressed. This leads to a reduction in venous return, and a concomitant reduction in cerebral blood flow.

Question 7

What four transporters are responsible for carrying glucose across the blood brain barrier, and on which cells are they found?

Answer 7

• Glut 1 has two isoforms:
  
  • 45 kD Glut 1 – Astrocytes
  • 55 kD Glut 1 – Microvessels, choroid plexus, ependymal cells.
• Glut 3 is found on neurons.
• Glut 5 is found on microglia.

Question 8

How do the blood vessels of the brain respond to changes in cerebral perfusion pressure?

Answer 8

As cerebral perfusion pressure goes up or down, the blood vessels will constrict or dilate to compensate – maintaining blood flow at a plateau. However, at the extremes, increased cerebral perfusion pressure will increase cranial blood flow, and decreased pressure will reduce cranial blood flow.

Question 9

How does the sympathetic nervous system affect cerebral blood flow and why?

What neurotransmitters are used by it?

Answer 9

Sympathetic innervation protects the brain by constricting when blood pressure is high via norepinephrine and neuropeptide Y.

This protects the brain.

Question 10

What are the four circumventricular organs and their functions?

Answer 10

1. Posterior pituitary
   
   1. Has secretory functions – we already know about this.
2. Area postrema
   
   1. Initiates vomiting in response to chemical triggers.
3. Organum vasculosum of the lamina terminalis (OVLT)
   
   1. Regulates total body water and thirst important as a target of angiotensin II
4. Subfornical organ
   
   1. Not sure what this does.

Question 11

When intracranial pressure increases or decreases, how does the body modify CSF levels to adapt to the change?

Answer 11

It either increases or decreases absorption to respond to the change.

Question 12

At equilibrium, what is the relationship of sodium and total osmolarity of CSF to the blood?

What is CSF richer in than the blood?

What is blood richer in the than the CSF?

Answer 12

At equilibrium, the level of sodium and the overall osmolarity of CSF is roughly equal to that of the blood.

However, CSF is richer in Cl-, and CO2. As a result, CSF is more acidic (pH ≅ 7.33)

On the other hand, protein, and glucose cannot enter the CSF, so the CSF will not have as much of these substances as the blood. Blood also contains more K+, Ca2+ and HCO3-(slightly)

Question 13

What protein is responsible for taking drugs out of the ventricles that have passed through the blood brain barrier but don’t belong there?

Answer 13

P-glycoprotein

Question 14

How does CO2 affect cerebral blood flow, and what causes the change?

Answer 14

As CO2 goes up, cerebral blood flow goes up (H+ is a vasodilator).

Question 15

What is the general idea of how water enters the ventricles?

Answer 15

N+/K+ ATPase creates electrochemical gradient for Na+, which causes a net efflux of Na+, HCO3-, and Cl- from the blood into the ventricles.

This creates an osmotic gradient that drives water into the ventricles.