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Traumatic brain injury

Descriptive

TitleInfo
Title
Traumatic brain injury
SubTitle
novel targets for potential therapies
Name (type = personal)
NamePart (type = family)
Swiatkowski
NamePart (type = given)
Przemyslaw
NamePart (type = date)
1987-
DisplayForm
Przemyslaw Swiatkowski
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Firestein
NamePart (type = given)
Bonnie L.
DisplayForm
Bonnie L. Firestein
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Alder
NamePart (type = given)
Janet
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Janet Alder
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Zhou
NamePart (type = given)
Renping
DisplayForm
Renping Zhou
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Cai
NamePart (type = given)
Li
DisplayForm
Li Cai
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
D'Arcangelo
NamePart (type = given)
Gabriella
DisplayForm
Gabriella D'Arcangelo
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2018
DateOther (qualifier = exact); (type = degree)
2018-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2018
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Traumatic brain injury (TBI) induces severe neurological damage leading to significant deficits in learning and memory and poor quality of life. It is a pathology that involves a variety of molecular and physiological responses, and in order to find an effective treatment these responses need to be addressed in a comprehensive manner. This study involves several approaches that aim to investigate specific proteins, molecular pathways, as well as cellular responses to brain injury. Cytosolic PSD-95 interactor (cypin), a guanine deaminase, regulates dendritic spine reemergence and promotes neuronal survival in an in vitro N-methyl-D-aspartate (NMDA) induced injury model of TBI. In this study, we identify novel small molecule activators, H9 and G5, and an inhibitor, B9, of cypin and show neuroprotective potential of cypin activators in vitro and in vivo in mice subjected to controlled cortical impact (CCI) injury. Hippocampal neurons pretreated with H9 or G5 display preserved physiology and survival after injury, phenotypes that are lost in cultures pretreated with B9 or when cypin is knocked down. Secondly, we expanded our scope and focused on the role of the PI3K/Akt/mTORC1 pathway in brain injury. We show that exposure to sublethal levels of NMDA does not alter phosphorylation of Akt, S6, and GSK3β at two and twenty-four hours following injury. Electrophysiological recordings show that NMDA-induced injury causes a significant decrease in spontaneous excitatory postsynaptic currents at both two and twenty-four hours, and this phenotype can be prevented by inhibiting mTORC1 or GSK3β, but not Akt. Additionally, inhibition of mTORC1 or GSK3β promotes neuronal survival following NMDA-induced injury. Thus, NMDA-induced excitotoxicity involves a mechanism that requires the permissive activity of mTORC1 and GSK3β, demonstrating the importance of these kinases in the neuronal response to injury. Finally, we investigated the role of microglia, the resident immune cells in the central nervous system, in brain injury using a combination of two-photon imaging, electrophysiology, and genetic tools. We show that ATP-induced outward current in microglia, which has been implicated in microglial chemotaxis in response to injury, is largely dependent on P2Y12R activation and mediated by G-proteins. Similarly, P2Y12R-coupled outward current is also evoked in response to laser-induced single neuron injury. Taken together, we progress our understanding of the complexity of brain injury using a multidimensional approach and propose new therapeutic targets for further investigation.
Subject (authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8664
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (vii, 132 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Brain--Wounds and injuries--Treatment
Note (type = statement of responsibility)
by Przemyslaw Swiatkowski
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3JQ148X
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Swiatkowski
GivenName
Przemyslaw
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-01-11 20:00:59
AssociatedEntity
Name
Przemyslaw Swiatkowski
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2018-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2020-01-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 31st, 2020.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

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2018-01-11T19:58:52
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2018-01-11T19:58:52
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