Modeling Steady State Intracranial Pressures in Microgravity

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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

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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)?

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Your Brain
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Cerebrospinal Fluid (CSF)
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A diagram of the lumped-parameter model
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Assumption 1 Fluid flow is driven by pressure
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Example Flow from the capillaries to the veins
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Filtration across the blood-brain barrier (BBB)
The Starling Landis Equation
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The Starling Landis Equation
Filtration across the blood-brain barrier
Hydrostatic pressure difference
Colloid osmotic pressure difference
Filtration Coefficient
Reflection Coefficient
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Colloid Osmotic Pressure
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Volume changes are accommodated via compliance
terms
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Assumption 2 Volume changes are proportional to
pressure difference changes
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• Example

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Conservation of Mass - Focus on Compartments
I,C,S,F,T,B
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Example Ventricular CSF Compartment (F) Rate of
Volume Change flow in flow out
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Doing this in each compartment yields
where
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The resulting system
has a unique steady state P defined by
and all solutions tend to P.
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Results

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.

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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.

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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

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CapillaryMembraneon Earth Tight
Proposed CapillaryMembranein Space Leaky
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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.

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• A leaky blood-brain barrier is modeled in QCB
  by either
• An increase in the filtration coefficient or
• A decrease in the reflection coefficient

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More leaky
With Normal BBB
6.3 mmHg drop in blood colloid osmotic
pressure No change in central venous pressure
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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

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References

• 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).
• 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).
• S. Stevens, W. Lakin, and P. Penar Modeling
  steady-state intracranial pressures in supine,
  head-down tilt, and microgravity conditions.
  Aviat Space Environ Med 76329-38 (2005)

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Extra Slides
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• Another Example
• One-way

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• Another Example

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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.