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Project Title:  A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats Reduce
Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2015  
End Date: 09/02/2021  
Task Last Updated: 12/13/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Rivera, Adreana  M.D. Houston Methodist Hospital 
Theriot, Corey  Ph.D. University of Texas Galveston 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: 2013 HERO NNJ13ZSA002N-Crew Health (FLAGSHIP & NSBRI) 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
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) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 9/2/2021 per PI and R. Schulte/HRP (jp).

NOTE: End date changed to 1/1/2021; note also with PI move to imec USA-Florida the PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2019 per HRP (Ed., 11/19/18)

Task Description: The etiology of the Spaceflight-Associated Neuro-Ocular Syndrome (SANS) (formerly called Visual Impariment Intracranial Pressure) is unknown. It is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with elevated intracranial pressure (ICP), may play a critical role. Cerebrospinal fluid (CSF) dynamics changes may be involved in the ICP increase. Leveraging on an existing hindlimb suspension (HS) analog in rats, we propose to study the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in these two processes of CSF dynamics, namely choroid plexus (CP) and arachnoid granulations (AG), respectively. On available tissue shared from the parent animal experiment (cohorts 3 and 4), we will perform differential gene expression profiling in the CP and AG of rats subjected to HS and their normal posture controls. In addition, we will compare the ultrastructure of the CP and AG and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporins and cellular junction proteins) of the CP and the endothelial cell layer of the venous sinuses, in normal posture and in HR rats within each cohort. The research groups involved in this proposal have the necessary resources and techniques in place at their laboratories in order to maximize the likelihood of success in this project. An anticipated product of this study is the reduction of the uncertainty in the likelihood or consequence of the visual impairment risk by gaining a study tool (validated animal model) and knowledge on the molecular basis of the biological processes involved in CSF dynamics changes generated by HS.

Research Impact/Earth Benefits: By understanding the processes associated with fluid shift and its concomitant increase in intracranial pressure (ICP), we anticipate gaining clues to reduce the impact of increased ICP in disease conditions like idiopathic intracranial hypertension and traumatic brain injury, as well as normal-pressure hydrocephalus.

Task Progress & Bibliography Information FY2021 
Task Progress: FINAL REPORTING DECEMBER 2021

Leveraging on an existing hindlimb suspension (HS) analog in rats, we studied the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in processes of cerebrospinal fluid (CSF) dynamics, namely choroid plexus (CP) and arachnoid villi (AV). On available tissue shared from the parent animal experiment, we performed differential gene expression profiling by RNA sequencing in the CP of rats subjected to HS and their normal posture controls, and in animals exposed to an enriched CO2 air composition versus those exposed to a normal atmosphere. The trasncriptomic profiles of each experimental group were clearly segregated, evidencing an effect of both the HS treatment and the 1% CO2 exposure.

In addition, we examined the ultrastructure of the CP and AV and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporin 4) in normal posture and in HS rats within each cohort. This work has demonstrated that these minute structures in the brain can be accessed for their investigation, gaining a study tool to elucidate the molecular basis of the biological processes involved in CSF dynamics changes generated by HS and CO2 exposure.

ANNUAL REPORTING JULY 2020

Currently, it is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with a chronic elevation of intracranial pressure (ICP), may play a critical role in the pathophysiology of the Spaceflight Associated Neuro-Ocular Syndrome (SANS). Changes in cerebrospinal fluid (CSF) dynamics might also be involved in the ICP increase. It is not known whether CSF production and/or outflow are altered in microgravity, but changes at the molecular and cellular level in the structures that produce and regulate the transcellular and paracellular secretion and reabsorption of CSF may be relevant. These structures are the choroid plexus (CP) and the arachnoid granulations, which in rodents are more rudimentary and called arachnoid villi (AV). Their morphology, ultrastructure, and gene expression profiles might be subject to change by conditions of weightlessness or cephalad fluid shifts. This project examines the responses to extended durations of rodent hindlimb suspension (HS) at various levels: (a) changes within the ultrastructure of the CP and AV, (b) the localization and distribution of key proteins involved in the production and reabsorption of CSF, and (c) the transcriptomic differences in the CP of rats subjected to HS compared to their normal posture controls. Male 9-month-old Long Evans rats were subjected to HS for 14 and 90 days, with a subset of animals completing 90-day HS further studied for recovery periods at normal posture of 14 and 90 days. All HS rats had age-matched cage controls. The rats were sacrificed under anesthesia and the brain carefully removed, cut in 5 mm-thick coronal blocks, and preserved for various analyses. Transmission electron microscopy of glutaraldehyde-fixed sections were used to evaluate the ultrastructure of the CP from the lateral ventricles and AV from the cerebral convexities. Samples stored in Bouin’s fixative were used for immunohistochemical analysis of specific targets involved in CSF regulation, such as aquaporins. In addition, similar coronal blocks were frozen without fixation for processing by laser capture microdissection to isolate RNA specifically from the CP for gene expression profiling by RNA sequencing analysis.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Zanello SB, Theriot CA, Chevez-Barrios P, Rivera A. "A gene expression and histologic approach to study production and outflow of cerebrospinal fluid in hindlimb suspended rats." 2022 NASA Human Research Program Investigators' Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators' Workshop, Virtual, February 7-10, 2022. , Feb-2022

Project Title:  A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats Reduce
Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2015  
End Date: 01/01/2021  
Task Last Updated: 08/11/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Rivera, Adreana  M.D. Houston Methodist Hospital 
Theriot, Corey  Ph.D. University of Texas Galveston 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Project Information: Grant/Contract No. 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2013 HERO NNJ13ZSA002N-Crew Health (FLAGSHIP & NSBRI) 
Grant/Contract No.: 80NSSC19K1666 ; Internal Project ; NNX15AW48G 
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) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 1/1/2021; note also with PI move to imec USA-Florida the PI's 3 projects were combined into one grant, 80NSSC19K1666 ; however, reporting will be required individually, per HRP (Ed., 11/4/19)

NOTE: End date changed to 9/30/2019 per HRP (Ed., 11/19/18)

Task Description: The etiology of the Spaceflight-Associated Neuro-Ocular Syndrome (SANS) (formerly called Visual Impariment Intracranial Pressure) is unknown. It is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with elevated intracranial pressure (ICP), may play a critical role. Cerebrospinal fluid (CSF) dynamics changes may be involved in the ICP increase. Leveraging on an existing hindlimb suspension (HS) analog in rats, we propose to study the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in these two processes of CSF dynamics, namely choroid plexus (CP) and arachnoid granulations (AG), respectively. On available tissue shared from the parent animal experiment (cohorts 3 and 4), we will perform differential gene expression profiling in the CP and AG of rats subjected to HS and their normal posture controls. In addition, we will compare the ultrastructure of the CP and AG and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporins and cellular junction proteins) of the CP and the endothelial cell layer of the venous sinuses, in normal posture and in HR rats within each cohort. The research groups involved in this proposal have the necessary resources and techniques in place at their laboratories in order to maximize the likelihood of success in this project. An anticipated product of this study is the reduction of the uncertainty in the likelihood or consequence of the visual impairment risk by gaining a study tool (validated animal model) and knowledge on the molecular basis of the biological processes involved in CSF dynamics changes generated by HS.

Research Impact/Earth Benefits: By understanding the processes associated with fluid shift and its concomitant increase in intracranial pressure (ICP), we anticipate gaining clues as to ways to mitigate and reduce the impact of increased ICP in disease conditions like idiopathic intracranial hypertension, glaucoma, and traumatic brain injury.

Task Progress & Bibliography Information FY2020 
Task Progress: This project studies the molecular bases of cerebrospinal fluid (CSF) production and outflow, and their modulation as a result of HS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid granulations or villi (AG/AV) and choroid plexus (CP) of HS rats compared to rats in normal posture. To date, transmission electron microscopy (TEM) has been performed in coronal micro-sections of the brain containing the CP and AV. Results are being interpreted. Laser capture micro-dissection of the CP and AV has been completed. The analysis of the isolated RNA is being conducted by RNA sequencing. Paraffin-embedded sections have been immunostained for GFAP (glial fibrillary acidic protein) and beta-amyloid and results are being collected.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2020
Project Title:  A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats Reduce
Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2015  
End Date: 09/30/2019  
Task Last Updated: 08/01/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Rivera, Adreana  M.D. Houston Methodist Hospital 
Theriot, Corey  Ph.D. University of Texas Galveston 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Project Information: Grant/Contract No. NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2013 HERO NNJ13ZSA002N-Crew Health (FLAGSHIP & NSBRI) 
Grant/Contract No.: NNX15AW48G 
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) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2019 per HRP (Ed., 11/19/18)

Task Description: The etiology of the Spaceflight-Associated Neuro-Ocular Syndrome (SANS) (formerly called Visual Impariment Intracranial Pressure) is unknown. It is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with elevated intracranial pressure (ICP), may play a critical role. Cerebrospinal fluid (CSF) dynamics changes may be involved in the ICP increase. Leveraging on an existing hindlimb suspension (HS) analog in rats, we propose to study the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in these two processes of CSF dynamics, namely choroid plexus (CP) and arachnoid granulations (AG), respectively. On available tissue shared from the parent animal experiment, we will perform differential gene expression profiling in the CP and AG of rats subjected to HS and their normal posture controls. In addition, we will compare the ultrastructure of the CP and AG and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporins and cellular junction proteins) of the CP and the endothelial cell layer of the venous sinuses. An anticipated product of this study is the reduction of the uncertainty in the likelihood or consequence of the SANS risk by gaining a study tool (validated animal model) and knowledge on the molecular basis of the biological processes involved in CSF dynamics changes generated by HS.

Research Impact/Earth Benefits: By understanding the processes associated with fluid shift and its concomitant increase in intracranial pressure (ICP), we will gain clues to mitigate and reduce the impact of increased ICP in disease conditions like idiopathic intracranial hypertension and traumatic brain injury.

Task Progress & Bibliography Information FY2018 
Task Progress: A NASA-funded study using the hindlimb suspension (HS) analog in rats to model the physiological changes observed in the Spaceflight-Associated Neuro-Ocular Syndrome (SANS) was conducted. Animal experimentation has been completed, and sample and data analysis is ongoing. The project proposes to study the molecular bases of cerebrospinal fluid (CSF) production and outflow, and their modulation as a result of HS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid granulations or villi (AG/AV) and choroid plexus (CP) of HS rats compared to rats in normal posture. To date, transmission electron microscopy (TEM) has been performed in coronal microsections of the brain containing the CP and AV, and laser capture microdissection of the CP and AV is being conducted in order to extract RNA from these specialized areas.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Zanello SB, Tadigotla V, Hurley J, Skog J, Stevens B, Calvillo E, Bershad E. "Inflammatory gene expression signatures in idiopathic intracranial hypertension: Possible implications in microgravity-induced ICP elevation." npj Microgravity. 2018 Jan 11;4(1):1. https://doi.org/10.1038/s41526-017-0036-6 ; PubMed PMID: 29354685; PubMed Central PMCID: PMC5764966 , Jan-2018
Articles in Peer-reviewed Journals Cromwell RL, Scott JM, Downs M, Yarbough PO, Zanello SB, Ploutz-Snyder L. "Overview of the NASA 70-day Bed Rest Study." Med Sci Sports Exerc. 2018 Sep;50(9):1909-19. Epub 2018 Mar 22. https://doi.org/10.1249/MSS.0000000000001617 ; PubMed PMID: 29570535 , Sep-2018
Project Title:  A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2015  
End Date: 09/30/2018  
Task Last Updated: 07/26/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Rivera, Adreana  M.D. Houston Methodist Hospital 
Theriot, Corey  Ph.D. University of Texas Galveston 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Project Information: Grant/Contract No. NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2013 HERO NNJ13ZSA002N-Crew Health (FLAGSHIP & NSBRI) 
Grant/Contract No.: NNX15AW48G 
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) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Task Description: The etiology of the Visual Impairment and Intracranial Pressure (VIIP) syndrome is unknown. It is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with elevated intracranial pressure (ICP), may play a critical role. Cerebrospinal fluid (CSF) dynamics changes may be involved in the ICP increase. Leveraging on an existing hindlimb suspension (HS) analog in rats, we propose to study the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in these two processes of CSF dynamics, namely choroid plexus (CP) and arachnoid granulations (AG), respectively. On available tissue shared from the parent animal experiment (cohorts 3 and 4), we will perform differential gene expression profiling in the CP and AG of rats subjected to HS and their normal posture controls. In addition, we will compare the ultrastructure of the CP and AG and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporins and cellular junction proteins) of the CP and the endothelial cell layer of the venous sinuses, in normal posture and in HR rats within each cohort. The research groups involved in this proposal have the necessary resources and techniques in place at their laboratories in order to maximize the likelihood of success in this project. An anticipated product of this study is the reduction of the uncertainty in the likelihood or consequence of the visual impairment risk by gaining a study tool (validated animal model) and knowledge on the molecular basis of the biological processes involved in CSF dynamics changes generated by HS.

Research Impact/Earth Benefits: By understanding the processes associated with fluid shift and its concomitant increase in intracranial pressure (ICP), we anticipate gaining clues as to ways to mitigate and reduce the impact of increased ICP in disease conditions like idiopathic intracranial hypertension, glaucoma, and traumatic brain injury.

Task Progress & Bibliography Information FY2017 
Task Progress: One of the responses to exposure to the microgravity spaceflight environment is a pronounced cephalic fluid shift. This project tests the hypothesis that this fluid shift is a causative factor in the ocular changes seen in astronauts during and following long-duration spaceflight. The study uses the well-documented rat hindlimb suspension (HLS) model to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. The experimental protocol uses HLS durations of 7, 14, 28, and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28, or 90 days. All HLS animals have age-matched cage controls. All animals have ad lib access to food and water. A 12:12 LD cycle is present. Eyes are collected at baseline, 7, 14, 28, and 90 days of HLS, and at 7, 14, 28, and 90 days of recovery, for histologic and gene expression evaluations. The study has started with the young adult male, young adult female, and old males cohorts. Comparing data between these cohorts will allow to determine if there is a gender and age difference in the responses. Following completion of these two groups, there will be one additional cohort exposed to elevated CO2 levels similar to those experienced on ISS (International Space Station). This last group will allow to determine if a mild (~1%) hypercapnic environment plays a role in the cephalic shift response and possible development of VIIP (Vision Impairment and Intracranial Pressure).

The continuation of this project entitled "A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats" addresses the mechanisms of production and resorption of cerebrospinal fluid in the brain at the molecular and histologic levels, and how these processes are affected by the fluid shift imposed by hindlimb suspension as a model of microgravity.

This study depends on the availability of tissue samples from collaborators at University of California (UC) Davis. Due to the schedule of collections and delays in the conduction of the study at UC Davis, this project is delayed accordingly. We anticipate samples to be provided during FY17.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2017
Project Title:  A Gene Expression and Histologic Approach to the Study of Cerebrospinal Fluid Production and Outflow in Hindlimb Suspended Rats Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/01/2015  
End Date: 09/30/2018  
Task Last Updated: 11/21/2014 
Download report in PDF pdf
Principal Investigator/Affiliation:   Zanello, Susana  Ph.D. / KBR/NASA Johnson Space Center 
Address:  Human Research Program Chief Scientist Office 
 
Houston , TX 77058 
Email: susana.b.zanello@nasa.gov 
Phone: 832-576-6059  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: KBR/NASA Johnson Space Center 
Joint Agency:  
Comments: NOTE (January 2021): PI now at KBR/NASA JSC as of December 2020. Previously at imec USA from June 2019-November 2020; NASA JSC (KBRwyle) from August 2017 until spring 2019. Prior to August 2017, PI was with Universities Space Research Association. 
Co-Investigator(s)
Affiliation: 
Rivera, Adreana  M.D. Houston Methodist Hospital 
Theriot, Corey  Ph.D. University of Texas Galveston 
Chevez-Barrios, Patricia  M.D. The Methodist Hospital Research Institute 
Project Information: Grant/Contract No. NNX15AW48G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2013 HERO NNJ13ZSA002N-Crew Health (FLAGSHIP & NSBRI) 
Grant/Contract No.: NNX15AW48G 
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) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) SANS-104:Determine whether ocular manifestations can be induced by fluid shifts in rodents and whether this model can be used for more detailed mechanistic insights (IRP Rev L)
Task Description: The etiology of the Visual Impairment and Intracranial Pressure (VIIP) syndrome is unknown. It is hypothesized that weightlessness-induced cephalad fluid shift, possibly associated with elevated intracranial pressure (ICP), may play a critical role. Cerebrospinal fluid (CSF) dynamics changes may be involved in the ICP increase. Leveraging on an existing hindlimb suspension (HS) analog in rats, we propose to study the molecular aspects of CSF production and outflow modulation as a result of HS in the tissues involved in these two processes of CSF dynamics, namely choroid plexus (CP) and arachnoid granulations (AG), respectively. On available tissue shared from the parent animal experiment (cohorts 3 and 4), we will perform differential gene expression profiling in the CP and AG of rats subjected to HS and their normal posture controls. In addition, we will compare the ultrastructure of the CP and AG and the histologic localization and distribution of putative targets implicated in CSF dynamics (aquaporins and cellular junction proteins) of the CP and the endothelial cell layer of the venous sinuses, in normal posture and in HR rats within each cohort. The research groups involved in this proposal have the necessary resources and techniques in place at their laboratories in order to maximize the likelihood of success in this project. An anticipated product of this study is the reduction of the uncertainty in the likelihood or consequence of the visual impairment risk by gaining a study tool (validated animal model) and knowledge on the molecular basis of the biological processes involved in CSF dynamics changes generated by HS.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2016 
Task Progress: New project for FY2016.

Bibliography Type: Description: (Last Updated: 12/14/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2016