Modeling Steady State

Intracranial Pressures in
Microgravity
• Scott A Stevens, PhD
Penn State Erie

• William D Lakin, PhD

The University of Vermont

• Paul L Penar, MD
The University of Vermont
 Motivation
• Many astronauts experience symptoms of
Space Adaptation Sickness during the first
few hours or days of spaceflight.

• The cause of all symptoms is not well

understood.

• We are investigating possible causes via

mathematical modeling.

Are some symptoms of SAS caused by

elevated intracranial pressure (ICP)?
Your Brain
Cerebrospinal Fluid (CSF)
A diagram of the lumped-parameter model
Assumption 1:
Fluid flow is driven by pressure
Pi  Pj
Qij   Z ij ( Pi  Pj )
Rij

Qij  Flow From Compartment i to j

Pi  Pressure in Compartment i
R ij  Resistance to flow
Zij  Fluidity  1/R ij
Example: Flow from the capillaries to the veins

PC  PS
QCS   Z CS ( PC  PS )
RCS
Filtration across the blood-brain barrier (BBB)

The Starling Landis Equation:

QCB  K CB [ ( PC  PB )   CB ( C   B ) ],
The Starling Landis Equation:
QCB  K CB [ ( PC  PB )   CB ( C   B ) ],

QCB = Filtration across the blood-brain barrier

PC  PB = Hydrostatic pressure difference

C  B = Colloid osmotic pressure difference

K CB = Filtration Coefficient

 CB = Reflection Coefficient
Colloid Osmotic Pressure
Volume changes are accommodated via compliance terms
Assumption 2: Volume changes are
proportional to pressure difference changes

dVij d dPi dPj

dt
 C ij [ Pi  Pj ]  Cij
dt dt
(

dt
)

dVij
 " Local" Volume Change
dt

Vi  Volume of Compartment i
Pi  Pressure in Compartment i
Cij  Local Compliance
Example:
dVCB dPC dPB dVC
dt
(
 CCB
dt
 )
dt

dt
Conservation of Mass - Focus on Compartments I,C,S,F,T,B
Example: Ventricular CSF Compartment (F)

Rate of Volume Change = flow in – flow out

C FB ( P  P )  QCF  Z FB ( PF  PB )  Z FT ( PF  PT )
F
'
B
'
Doing this in each compartment yields:

dP
C ZP  Q
dt
where

 PI   Z AI PA  QIC 
P   Q  Q  K  (   ) 
 C  IC CF CB CB C B 
 PS   Z SV PV 
P   , and Q Q

 PF   CF 
 PB    K CB  CB ( C   B ) 
   dPA dPV dPY 
 PT  C AT  CTV  CTY  Z TV PV 
 dt dt dt 
The resulting system;

dP
C ZP  Q
dt
has a unique steady state P* defined by

ZP  Q
* *

and all solutions tend to P*.

 Results
* * *
PF  PF  P F  ( PV  PV )  0.37( C   C )
* * *
PB  PB  P B  ( PV  PV )  0.37( C   C )

1. Intracranial pressures (PF and PB) change in

parallel with the changes in central venous
pressure (PV).

2. Intracranial pressures increase 0.37 mmHg for

every one mmHg decrease in blood colloid
osmotic pressure.
 Conclusions:
1. Microgravity probably does not initiate intracranial
hypertension.

2. The intracranial pressure (ICP) in microgravity

may be less than that experienced lying
down on earth.

3. The sickness associated with microgravity is

probably not due to intracranial hypertension
unless microgravity alters additional physiology.
Consider possible alterations in the
blood-brain barrier (BBB) in space.

Possible Causes:

•The lack of orthostatic pressure

in microgravity.

• Radiation effects above low earth orbit

Capillary
Membrane
on Earth:
Tight

Proposed
Capillary
Membrane
in Space:
Leaky
 Radiation effects on the BBB
• Leszczynski et al [1,2] (2002, 2004)

- Cell phone radiation levels caused increases in the

protein expression of hsp27 and p38MAPK in human
endothelial cells.

- It is hypothesized [1] that activation of hsp27 may

cause an increase in blood-brain barrier permeability.

• Radiation exposure in space appears capable of

adversely impacting the integrity of the blood-brain
barrier.
A “leaky” blood-brain barrier is
modeled in QCB by either

• An increase in the filtration coefficient

or

• A decrease in the reflection coefficient

 More leaky
With
Normal
BBB

6.3 mmHg drop in blood colloid osmotic pressure

No change in central venous pressure
 Conclusions
• If there is no alteration in the blood-brain
barrier, it seems unlikely that ICP in
microgravity is significantly higher than that
experienced lying down on earth.

• If the integrity of the barrier is reduced in

microgravity then it is possible that intracranial
hypertension causes some of the symptoms
of Space Adaptation Sickness
 References

1. D. Leszczynski, S. Joenvaara, J. Reivinen, and R. Kuokka: Non-thermal

activation of the hsp27/p38MAPK stress pathway by mobile phone
radiation in human endothelial cells: Molecular mechanism for cancer-
and blood-brain barrier-related effects. Differentiation 70: 120-129
(2002).

2. D. Leszczynski, R. Nylund, S. Joenvaara, and J. Reivinen: Applicability

of discovery science approach to determine biological effects of mobile
phone radiation. Proteomics 4: 426-431 (2004).

3. S. Stevens, W. Lakin, and P. Penar: Modeling steady-state intracranial

pressures in supine, head-down tilt, and microgravity conditions. Aviat
Space Environ Med 76:329-38 (2005)
Extra Slides
• Another Example
QSV  Z SV ( PS  PV )
• One-way

QTS  Z TS ( PT  PS )

QTV  Z TV ( PT  PV )
 Another Example

dVS dPS dPT dPS dPB

 CTS (  )  C BS (  )
dt dt dt dt dt
  Z AI 0 0 0 0 0 
 0 K CB Z CS  Z CS 0  K CB 0 
 
 0  Z CS Z CS , SV ,TS 0 0  Z TS 
Z  
 0 0 0 Z FB , FT  Z FB  Z FT 
 0  K CB 0  Z FB K CB  Z BT , FB  Z BT 
 
 0 0  ZTS  Z FT  Z BT Z BT , FT ,TS ,TV 

Z BT , FB  Z BT Z FB .
  C IB 0 0 0  C IB 0 
 
 0 C CB 0 0  C CB 0 
 0 0 C BS ,TS 0  C BS  CTS 
C 
 0 0 0 C FB  C FB 0 
 C  C CB  C BS  C FB C BS , BT ,CB , FB , IB  C BT 
 IB 
 0 0  CTS 0  C BT C AT , BT ,TS ,TV ,TY 
Radiation Effects on BBB
Recent experiments on Earth by Leszczynski et al. involving cell
phone radiation demonstrate the potential effect that exposure to
even small amounts of radiation in space can have on the blood-
brain barrier [1,2]. As reported in these studies, the mobile phone
radiation activated non-thermal transient changes in the protein
expression levels of hsp27 and p38MAPK in human endothelial cells.
It is hypothesized in [1] that activation of hsp27 may cause an
increase in blood-brain barrier permeability through stabilization of
endothelial cell stress fibers. Increased protein activity may even
cause the endothelial cells themselves to shrink, lessening their
volume, widening the junction gap, and reducing the overlap region.
As a result, radiation exposure in space appears capable of
adversely impacting the integrity of the blood brain barrier.