Modeling Steady State Intracranial Pressures in

Microgravity

• Scott A Stevens, PhDPenn State Erie

• William D Lakin, PhDThe University of Vermont

• Paul L Penar, MDThe 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

)( jiijij

jiij PPZ

R

PPQ

ijij

ij

i

ijQ

1/R Fluidity Z

flow toResistance R

it Compartmenin Pressure P

j toit Compartmen From Flow

)( SCCSCS

SCCS PPZ

R

PPQ

Example: Flow from the capillaries to the veins

],)()([ BCCBBCCBCB PPKQ

Filtration across the blood-brain barrier (BBB)

The Starling Landis Equation:

],)()([ BCCBBCCBCB PPKQ

CBQ

BC PP

CBK

The Starling Landis Equation:

BC

CB

= Hydrostatic pressure difference

= Filtration across the blood-brain barrier

= Filtration Coefficient

= Reflection Coefficient

= Colloid osmotic pressure difference

Colloid Osmotic Pressure

Volume changes are accommodated via compliance terms

Assumption 2: Volume changes are proportional to pressure difference changes

Compliance Local C

it Compartmenin Pressure P

it Compartmen of Volume V

Change Volume Local""

i

ij

i

ij

dt

dV

)(][dt

dP

dt

dPCPP

dt

dC

dt

dV jiijjiij

ij

Example:

dt

dV

dt

dP

dt

dPC

dt

dV CBCCB

CB )(

Conservation of Mass - Focus on Compartments I,C,S,F,T,B

)()()( ''

TFFTBFFBCFBFFB PPZPPZQPPC

Example: Ventricular CSF Compartment (F)

Rate of Volume Change = flow in – flow out

QZPdt

dPC

Doing this in each compartment yields:

where

VTVY

TYV

TVA

AT

BCCBCB

CF

VSV

BCCBCBCFIC

ICAAI

T

B

F

S

C

I

PZdt

dPC

dt

dPC

dt

dPC

K

Q

PZ

KQQ

QPZ

Q

P

P

P

P

P

P

P

)(

)(

and,

QZPdt

dPC

The resulting system;

** QZP

has a unique steady state P* defined by

and all solutions tend to P*.

)*(37.0)*(*CCVVFFF PPPPP

)*(37.0)*(*CCVVBBB PPPPP

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.

Results

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.

Conclusions:

Possible Causes:

Consider possible alterations in the blood-brain barrier (BBB) in space.

•The lack of orthostatic pressure in microgravity.

• Radiation effects above low earth orbit

CapillaryMembraneon Earth:Tight

ProposedCapillaryMembranein 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

With Normal

BBB

More leaky

6.3 mmHg drop in blood colloid osmotic pressureNo 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

• One-way

)( VSSVSV PPZQ

)( STTSTS PPZQ

)( VTTVTV PPZQ

Another Example

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dt

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dP

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dt

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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.