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Project Title:  Effects of Microgravity on Intracranial Pressure Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2012  
End Date: 10/31/2015  
Task Last Updated: 03/10/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Hastings, Jeffrey  The University of Texas Southwestern Medical Center 
Whitworth, Louis  The University of Texas Southwestern Medical Center 
Williams, Michael  University of Washington 
Zhang, Rong  The University of Texas Southwestern Medical Center 
Project Information: Grant/Contract No. NCC 9-58-CA02801 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-CA02801 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 10/31/2015 per NSBRI (Ed., 9/25/15)

Task Description: Humans have been travelling in space for more than 40 years without clear evidence of visual impairment in astronauts. However very recently, it has been identified that some astronauts on the International Space Station (ISS) seem to be at risk for visual changes that may be due to elevated pressure inside the head (intracranial pressure (ICP)). It is well known that there is a relative shift in fluid towards the head in humans during space flight (microgravity) and therefore these changes may increase intracranial pressure to a greater degree than previously appreciated. Intracranial pressure may also be exacerbated or transiently elevated by small increases in the partial pressure of carbon dioxide in the International Space Station atmosphere and during strength training exercise that is employed to try and maintain astronaut's muscle mass. Therefore, the primary aim of this project will be to provide novel data about the impact of microgravity induced central fluid shifts on directly measured intracranial pressure, and the associated inflow and outflow of blood to the brain, accompanied by simultaneous assessment of structural changes in the eye. Furthermore, we will examine the above factors during small changes in atmospheric carbon dioxide and during strength training exercise in simulated microgravity. This information is entirely unknown and absolutely essential to establishing the pathophysiology of the recently identified visual impairments in some long duration astronauts, so as to develop appropriate countermeasures.

Research Impact/Earth Benefits: The project has implications for public health by providing a better understanding of the regulation of intracranial pressure in normal healthy individuals and thus will offer an improved knowledge base to provide effective treatments for a wide range of intracranial disorders. We have clarified the key component of the physiology of the intracranial space in microgravity, which will go a long way to eliminating the Vision Impairment and Intracranial Pressure (VIIP) syndrome. We have developed a collaboration with Under Armour, Inc., to develop a wearable garment to deliver lower body negative pressure (LBNP) and reduce ICP not only in space, but also on Earth. For example, a major Earth-based benefit to society will be the application of LBNP in a clinical environment. Alongside pharmacological interventions, placing patients with intracranial hypertension in the semi-recumbent position is standard practice to lower ICP. This slight hydrostatic gradient reduces ICP, whilst maintaining arterial blood pressure and thus cerebral perfusion pressure. LBNP may provide a more controlled and robust intervention within a hospital and field-based environment. Indeed, pathological pressure waves are often observed during sleep when patients are in the supine position. Nocturnal LBNP may provide a novel method to lower mean ICP and improve intracranial stability during this critical period. Given our robust observation that simply placing the head on a pillow lowers ICP, the combination of low level LBNP and head elevation may prove optimal. If a practical and comfortable device is developed, LBNP could also be used to reduce the incidence of chronic headache in patients with pseudotumor cerebri (raised ICP), as well as patients with traumatic brain injury.

Task Progress & Bibliography Information FY2016 
Task Progress: Overall Task Progress: All objectives were met and all aims were accomplished for this study. This past year was notable for our second parabolic flight campaign during which we were able to recruit 3 women to create our final cohort of 8 subjects (5 men; 3 women).

Bibliography Type: Description: (Last Updated: 09/27/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Lawley JS, Levine BD, Williams MA, Malm J, Eklund A, Polaner DM, Subudhi AW, Hackett PH, Roach RC. "Cerebral spinal fluid dynamics: Effect of hypoxia and implications for high-altitude illness." J Appl Physiol (1985). 2016 Jan 15;120(2):251-62. Review. Epub 2015 Oct 22. http://dx.doi.org/10.1152/japplphysiol.00370.2015 ; PubMed PMID: 26494441 , Jan-2016
Awards Levine BD. (Benjamin D. Levine) "Fellow, American Heart Association, February 2015." Feb-2015
Awards Levine BD. "NASA, Most Compelling Results from the 2013 International Space Station, May 2014." May-2014
Significant Media Coverage Frisinger C. "Online News Article, 'Cancer Patients Helping UT Southwestern Scientists and NASA Study Pressure Inside the Brain During Zero Gravity.' " UT Southwestern Medical Center News Center online, August 19, 2015. http://www.newswise.com/articles/cancer-patients-helping-ut-southwestern-scientists-and-nasa-study-pressure-inside-the-brain-during-zero-gravity , Aug-2015
Significant Media Coverage Wheeler J. "Online News Article, 'Dallas Cancer Survivor Helps Astronauts Facing Vision Loss.' " WFAA ABC online news, August 26, 2015. http://www.wfaa.com/story/news/health/2015/08/26/dallas-cancer-survivor-helps-astronauts-facing-vision-loss/32361761/ , Aug-2015
Significant Media Coverage Silverman L. "Online News Article, 'Dallas Cancer Patient Takes A Trip in Zero Gravity For Research.' " KERA News Blog, September 1, 2015. http://breakthroughs.kera.org/dallas-cancer-patient-takes-a-trip-in-zero-gravity-for-research/ , Sep-2015
Significant Media Coverage Brown L. "Online News Article, 'N. TX Cancer Survivor Helping in Study of Astronauts, Vision Loss.' " Fox 4 online news, July 20, 2015. http://www.fox4news.com/story/29591381/n-tx-cancer-survivor-helping-in-study-of-astronauts-vision-loss , Jul-2015
Significant Media Coverage Young ME. "Online News Article, 'Cancer Survivors Volunteer for Tests that May Save Astronauts' Vision.' " Dallas Morning News online, August 25, 2015. http://www.dallasnews.com/news/metro/20150826-cancer-survivors-volunteer-for-tests-that-may-save-astronauts-vision.ece , Aug-2015
Significant Media Coverage Allen S. "Online News Article, 'Pauls Valley Cancer Patient Participates in NASA Study in Zero-Gravity Environment.' " The Oklahoman online news, August 24, 2015. http://newsok.com/pauls-valley-cancer-patient-participates-in-nasa-study-in-zero-gravity-environment/article/5442145 , Aug-2015
Significant Media Coverage Avril T. "Online News Article, 'Cancer survivor helps solve astronaut eye problems.' " Philadelphia Inquirer, Philly.com online news, September 7, 2015. http://www.philly.com/philly/health/20150906_Cancer_survivor_helps_solve_astronaut_eye_problems.html , Sep-2015
Project Title:  Effects of Microgravity on Intracranial Pressure Reduce
Fiscal Year: FY 2015 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2012  
End Date: 10/31/2015  
Task Last Updated: 11/17/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Hastings, Jeffrey  The University of Texas Southwestern Medical Center at Dallas 
Whitworth, Louis  The University of Texas Southwestern Medical Center at Dallas 
Williams, Michael  Sinai Hospital of Baltimore, Inc. 
Zhang, Rong  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02801 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-CA02801 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date changed to 10/31/2015 per NSBRI (Ed., 9/25/15)

Task Description: Humans have been travelling in space for more than 40 years without clear evidence of visual impairment in astronauts. However, very recently, it has been identified that some astronauts on the International Space Station seem to be at risk for visual changes that may be due to elevated pressure inside the head (intracranial pressure). It is well known that there is a relative shift in fluid towards the head in humans during space flight (microgravity) and therefore these changes may increase intracranial pressure to a greater degree than previously appreciated. Intracranial pressure may also be exacerbated or transiently elevated by small increases in the partial pressure of carbon dioxide in the International Space Station atmosphere and during strength training exercise that are employed to try and maintain astronaut's muscle mass. Therefore, the primary aim of this project will be to provide novel data about the impact of microgravity induced central fluid shifts on directly measured intracranial pressure, and the associated inflow and outflow of blood to the brain, accompanied by simultaneous assessment of structural changes in the eye. Furthermore, we will examine the above factors during small changes in atmospheric carbon dioxide and during strength training exercise in simulated microgravity. This information is entirely unknown and absolutely essential to establishing the pathophysiology of the recently identified visual impairments in some long duration astronauts, so as to develop appropriate countermeasures.

Research Impact/Earth Benefits: The project will have implications for public health and will provide a better understanding of the regulation of intracranial pressure in normal healthy individuals and thus will offer an improved knowledge base to provide effective treatments for a wide range of intracranial disorders.

Task Progress & Bibliography Information FY2015 
Task Progress: Institutional Review Board approval for this investigation has been obtained. 3 subjects have completed the bedrest protocol and 4 subjects have completed the flight experiment protocol.

Bibliography Type: Description: (Last Updated: 09/27/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2015
Project Title:  Effects of Microgravity on Intracranial Pressure Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2012  
End Date: 09/30/2015  
Task Last Updated: 10/16/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Hastings, Jeffrey  The University of Texas Southwestern Medical Center at Dallas 
Whitworth, Louis  The University of Texas Southwestern Medical Center at Dallas 
Williams, Michael  Sinai Hospital of Baltimore, Inc. 
Zhang, Rong  The University of Texas Southwestern Medical Center at Dallas 
Project Information: Grant/Contract No. NCC 9-58-CA02801 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-CA02801 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Task Description: Humans have been travelling in space for more than 40 years without clear evidence of visual impairment in astronauts. However, very recently, it has been identified that some astronauts on the International Space Station seem to be at risk for visual changes that may be due to elevated pressure inside the head (intracranial pressure). It is well known that there is a relative shift in fluid towards the head in humans during space flight (microgravity) and therefore these changes may increase intracranial pressure to a greater degree than previously appreciated. Intracranial pressure may also be exacerbated or transiently elevated by small increases in the partial pressure of carbon dioxide in the International Space Station atmosphere and during strength training exercise that is employed to try and maintain astronaut's muscle mass. Therefore, the primary aim of this project will be to provide novel data about the impact of microgravity induced central fluid shifts on directly measured intracranial pressure, and the associated inflow and outflow of blood to the brain, accompanied by simultaneous assessment of structural changes in the eye. Furthermore, we will examine the above factors during small changes in atmospheric carbon dioxide and during strength training exercise in simulated microgravity. This information is entirely unknown and absolutely essential to establishing the pathophysiology of the recently identified visual impairments in some long duration astronauts, so as to develop appropriate countermeasures.

Research Impact/Earth Benefits: The project will have implications for public health and will provide a better understanding of the regulation of intracranial pressure in normal healthy individuals and thus will offer an improved knowledge base to provide effective treatments for a wide range of intracranial disorders.

Task Progress & Bibliography Information FY2014 
Task Progress: Institutional Review Board approval for this investigation has been obtained. We have completed extensive pilot testing and began the enrollment of three subjects. Other recruitment efforts are underway.

Bibliography Type: Description: (Last Updated: 09/27/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2014
Project Title:  Effects of Microgravity on Intracranial Pressure Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2012  
End Date: 09/30/2015  
Task Last Updated: 10/23/2012 
Download report in PDF pdf
Principal Investigator/Affiliation:   Levine, Benjamin D M.D. / The University of Texas Southwestern Medical Center at Dallas 
Address:  Institute for Exercise and Environmental Medicine (IEEM) 
7232 Greenville Ave, Suite 435 
Dallas , TX 75231-5129 
Email: benjaminlevine@texashealth.org 
Phone: 214-345-4619  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: The University of Texas Southwestern Medical Center at Dallas 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Hastings, Jeffrey  The University of Texas Southwestern Medical Center at Dallas  
Whitworth, Louis  The University of Texas Southwestern Medical Center at Dallas  
Zhang, Rong  The University of Texas Southwestern Medical Center at Dallas  
Williams, Michael  Sinai Hospital of Baltimore, Inc. 
Project Information: Grant/Contract No. NCC 9-58-CA02801 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-CA02801 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) VIIP:Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations (IRP Rev E)
Human Research Program Gaps: (1) VIIP01:We do not know the etiological mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight and postflight (IRP Rev E)
Task Description: Lately, some astronauts have experienced visual changes that could be due to increased pressure in the brain. However the mechanism(s) underlying this problem remain unknown. The current working model is that microgravity induced fluid shifts increase intracranial pressure (ICP) and may be exacerbated by increases in the partial pressure of carbon dioxide in the ISS atmosphere or exercise. However the scientific community has been fooled before regarding expected and measured effects of microgravity on fluid compartment pressures! For example, central venous pressure (CVP) was expected to increase in space but actually fell to zero in microgravity. Also, it is hard to conceive of how the ICP in space could be greater than that which is routinely experienced on the ground in the recumbent posture. Millions of patients and thousands of research volunteers have been confined to bed for prolonged periods of time, and to our knowledge, there has never been a case of bed-rest induced blindness. Unfortunately, despite the enthusiasm for methods to measure ICP non-invasively, none are robust or reliable, and none have been validated in normal individuals without intracranial pathology. The only way to obtain this knowledge with confidence is to make direct, invasive measurements of ICP during relevant changes in hydrostatic gradients. Moreover, concomitant evaluation of inflow (arterial) and outflow (venous) pressures and flows are essential to build the science base of the effect of gravitational gradients on intracranial hemodynamics. The primary objective of this application is to make the first direct, invasive measurements of ICP and cerebral hemodynamics during changes in hydrostatic gradients induced by simulated (bedrest) and real (parabolic flight) microgravity. In order to accomplish these objectives, we propose to test the following hypotheses: Hypothesis 1: The transition from upright to supine posture increases intracranial and venous pressures that result in minimal changes in cerebral blood flow, oxygen delivery, and cerebral autoregulation. Additional gravitational loading and unloading by maneuvers result in small additional changes compared to the difference from standing to supine. Hypothesis 2: True microgravity induced by parabolic flight will produce cerebrovascular changes that are qualitatively, and quantitatively similar to those observed during bedrest. To test these hypotheses, we will accomplish the following specific aims:

Specific Aim 1: Our outstanding team of clinical scientists will recruit patients whom have been cured of a cancer or brain infection and whom have had direct access to the brain obtained via an Ommaya reservoir placed to allow prophylactic brain chemotherapy. Such patients have no intracranial or cardiovascular pathology, and have easy access to direct measurement of ICP with little risk. Simultaneous measurement of jugular venous pressure (PICC line) and intra-arterial pressure (arterial line or Finapres) will be combined with echo-Doppler ultrasound of the middle cerebral artery (transcranial Doppler) carotid and jugular size, velocity, and flow, plus near infrared spectroscopy to assess oxygen delivery/utilization to allow a comprehensive assessment of cerebrovascular hemodynamics during routine gravitational transients. Measurements will be repeated with modest increases in PaCO2, and during aerobic and strength exercise to determine the independent and additive effects of these baffling stimuli.

Specific Aim 2: The same patients as in Aim 1 will be invited to participate in a second study involving parabolic flight to achieve true microgravity. The same instrumentation will allow contrast between real microgravity, and usual terrestrial changes in hydrostatic gradients during daily life. Similar to aim 1, measurements will be obtained at rest, during exercise, and during small increases in PaCO2 (10 parabolas each).

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2013 
Task Progress: New project for FY2013.

Bibliography Type: Description: (Last Updated: 09/27/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2013