General Neurophysiology Lecture (Dr. Karius)

Question 1

Cerebrospinal Fluid

Answer 1

• 150 mL at any given moment
• Not, recirculated, so makes about 550 mL/day
• Most of the CSF (50 - 70%) is made by the specialized tissue of the CHOROID PLEXUS
• The remaining CSF is made by the Tissue that LINES the VENTRICLES and BLOOD VESSELS

Question 2

Cerebrospinal Fluid

TWO STAGE PROCESS

Answer 2

Step 1: Passive FILTRATION of Serum

Step 2: HCO3, Cl, and K Concentrations controlled by Channels on Epithelial Cells. AQUAPORINS also exist

IMPORTANT NOTE: Production of CAF is CONSTANT over a WIDE RANGE of Intracranial Pressures

Question 3

Items in EQUAL Concentration between Plasma and CSF

Answer 3

1) Na+
2) Cl-
3) HCO3

Question 4

Items where [CSF] > [Plasma]

Answer 4

1) Mg++

2) CO2

Question 5

Items where [CSF]

Answer 5

1) K+
2) Ca++
3) Protein
4) Glucose

Question 6

Cerebrospinal Fluid Flow

Answer 6

• CSF flows through the VENTRICULAR SYSTEM. However, the Flow is ONE WAY and the CSF must be REABSORBED at the END
• The CSF flows through VENTRICLES, through the different FORAMEN

Question 7

Cerebrospinal Fluid Absorption

Answer 7

1) ABSORPTION of CSF by 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
• Absorption of CSF is PROPORTIONAL to Intracranial Pressure
  a) At Pressures below 68mm CSF, NO ABSORPTION
  b) Normal Pressure ~ 112mm CSF
• INCREASED Pressure causes DAMAGE to Neurons
  2) From the Arachnoid Villi, the CSF enters the VENOUS SINUSES by BULK FLOW

**The ROLE of the CSF is to PROTECT the Brain (Weight in Air: 1400g; Weight in CSF: 50g; Effect of CSF: Priceless)

Question 8

Blood Brain Barrier

Answer 8

A) Capillaries in Brain have Two Components that Limit Exchange:

1) TIGHT JUNCTIONS between Endothelial Cells
2) GLIAL ENDFOOT come in Close Contact with Blood Vessels

B) Passive Diffusion:

1) H2O
2) CO2
3) O2
4) FREE Steroid Hormones (Most are Protein Bound)

C) What is the Major Energy Source for Neurons?
- GLUCOSE, which does NOT cross the Blood Brain Barrier readily

Question 9

Blood Brain Barrier and Glucose

Answer 9

GLUCOSE:
- GLUT1 Transporter!!!!!!

• NOT Insulin Dependent
• Two Forms (45 and 55K)
  a) 55K on CAPILLARIES
  b) 45K on ASTROGLIA

Question 10

Blood Brain Barrier and Na/K/2Cl Transporter

Answer 10

Na/K/2Cl Transporter:
- Moves ALL those ions fro CSF to Blood

• Expression tied to ENDOTHELIN 1 and 3
  a) Endothelin production tied to a Signal from the ASTROCYTES

b) May be related to [K+]CSF

Question 11

Blood Brain Barrier and Drugs

Answer 11

• Many drugs DO CROSS the BBB but are MOVED BACK to the Blood via P-GLYCOPROTEIN!!!!!!!!!!

Question 12

Blood Brian Barrier Function

Answer 12

1) The BBB exists to PROTECT the Chemical Composition of the CSF from BLOOD-BORNE AGENTS

2) Maintain ELECTROLYTE COMPOSITION
a) Particularly related to K+
b) Maintenance of Vm

3) Protection from TOXINS
4) Prevent ESCAPE of Neurotransmitters

Question 13

Several Places where the Brain is exposed to the Blood

Answer 13

• In these regions the Capillaries do NOT have the Tight Junctions between Endothelial Cells
• The CIRCUMVENTRICULAR ORGANS are Neural Tissue that is “Outside” or not as well protected by the BBB as other Neural Tissue. There are FOUR Regions that fall in this Category

1) AREA 1: The POSTERIOR PITUITARY
- The Neurohypophysis
- Modified NEURAL TISSUE
- Release Hormones into Blood

2) AREA 2: Area POSTREMA
- Vomiting

3 & 4) AREAS 3 and 4: ORGANUM VASCULOSUM of the LAMINA TERMINALS (OVLT)

• Subfornical Organ
• Both are involved in Control of Body Water/ Thirst/ Blood Volume Control (Angiotensin)

PURPOSE: Allow certain parts of the Brain to access the Plasma Composition

CONSEQUENCE: These areas are also exposed to Toxins that the rest of the Brain is PROTECTED from

Question 14

Cerebral Circulation

Answer 14

• 750 mL/min REQUIRED (14% of CO)

IMPORTANT DETAIL ABOUTN ARTERIAL FLOW:
- The 2 Internal Carotids and the Basilar Artery Join to form the CIRCLE OF WILLIS

• Despite appearance, there is little mixing of the Blood from the different sources
• IMPACT: Disruption of one of the Inputs produces LOCALIZED (Discrete) areas of Ischemia

Question 15

Cerebral Circulation

SYMPATHETIC INNERVATION

Answer 15

SYMPATHETIC:
- Neurotransmitters: Norepinephrine and NPY

• Receptors: Alpha Adrenergics
• Leads to CONSTRICTION when Systemic Cardiac Output/ Blood Pressure INCREASES****

Question 16

Cerebral Circulation

PARASYMPATHETIC INNERVATION

Answer 16

PARASYMPATHETIC:
- Large Blood Vessels

• ACH
• Vasoactive Intestinal Polypeptide (VIP)!!!!!!!!!!!!!!
• PHM-27 (derived from Pre-Pro-VIP)!!!!!!!!!!!!!!!!!!
• Cause VASODILATION**

Question 17

Cerebral Circulation

SENSORY INNERVATION

Answer 17

• There is Sensory Innervation of the Distal Blood Vessels

NEUROTRANSMITTERS:

1) Substance P (Dilation)
2) Neurokinin A (Dilation)
3) CGRP (Dilation)
* MOST DILATE***

• These Sensory Fibers render the Blood Vessels of the Brian Extremely SENSITIVE to Torsion/ Manipulation—-> LEADS TO PAIN
• In the Presence of REDUCED CSF Volume, the Brain is effectively HEAVIER and Simple Motion can cause pain because of the “TORSION” of the Blood Vessels
• The activation of those AFFERENT will also cause VASODILATION and INCREASE BLOOW FLOW (Returns Total Intracranial Volume closer to Normal?)

Question 18

Cerebral Circulation: Control

Answer 18

• Cerebral Blood flow is under LOCAL Control: OXYGEN CONSUMPTION dictates where in Brain the Blood will go
• Cerebral Blood Flow is STRONGLY influenced by Intracranial Pressure, as Intracranial Pressure goes up, Venous OUTFLOW is Obstructed, leading to REDUCED ARTERIAL FLOW!!!!!!
• Cerebral Blood flow is STRONGLY AUTOREGUALTED, that is, it is held constant over a WIDE RANGE of SYSTEMIC (Mean Arterial) Blood Pressures
• In the face of HIGH BLOOD PRESSURE (Which could damage the Blood Brain Barrier), Sympathetics in the Brain will VASOCONSTRICTOR the Vasculature
  a) Although this will INCREASE the Systemic Vascular Resistance, IT PROTECTS THE CAPILLARIES IN THE BRAIN FROM DAMAGE

Question 19

Cerebral Circulation- Effects on MAP

Answer 19

• A Decrease in Brain Perfusion will activate the Vasomotor Centers and INCREASE SYSTEM BP, sometimes Drastically

Question 20

What might Increase the Intracranial Pressure?

Answer 20

1) Hydrocephalus of any Variety
2) Edema
3) Bleeding within the Skull

Question 21

Systemic Effects when Blood Flow is Compromised

Answer 21

• If Blood Flow is compromised, the Brain will drive Systemic Blood Pressure UP to force Blood to the Brain
• Consequences: Systemic Blood Pressure can be DRIVEN to VERY HIGH LEVELS in order to Perfuse the Brain