dc.contributor.author |
Möderscheim, Tanja Anna Elisabeth |
en |
dc.date.accessioned |
2007-07-03T21:02:08Z |
en |
dc.date.available |
2007-07-03T21:02:08Z |
en |
dc.date.issued |
2006 |
en |
dc.identifier.citation |
Thesis (PhD--Physiology)--University of Auckland, 2006. |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/612 |
en |
dc.description.abstract |
Brain injuries such as stroke and birth asphyxia cause major physical and cognitive disabilities.
Accumulating evidence shows that the injured brain produces growth factors as an endogenous
protective and regenerative mechanism. Several of these factors have been identified and include
insulin-like growth factor-I, transforming growth factor and fibroblast growth factor. Recent
work in our laboratory has shown that the growth hormone axis is also upregulated following
hypoxic ischemic injury to the juvenile rat brain. Importantly, central treatment with growth
hormone offered strong neuroprotection in this model.
In vitro studies reported in this thesis have confirmed the neuroprotective properties of growth
hormone. Growth hormone-induced neuroprotection occurs via a neuronal brain-specific growth
hormone receptor, which behaves differently from that found in the periphery. Whereas both
ligands are strongly somatogenic in the periphery, rat but not bovine growth hormone had strong
neuroprotective, neurotrophic and gliatrophic effects in cortical primary cultures. This distinct
ligand specificity agrees with previous in vivo studies in our laboratory. Further, I show for the
first time that the prolactin axis, which is closely related to the growth hormone axis, is also
upregulated within the injured brain. Surprisingly, central treatment with prolactin failed to offer
neuroprotection. Immunohistochemistry however showed that prolactin and its receptor were
strongly and primarily upregulated on reactive glia in the penumbra, with limited staining on
neurons. This neuronal staining contrasts with a persistent and intense staining for the growth
hormone receptor and the growth hormone binding protein on these cells. The lack of any
neuroprotective effect of prolactin in vivo was confirmed using primary cortical cultures. In these
cultures, prolactin had only gliatrophic effects. These findings indicate a primary role for
prolactin in glial wound responses following brain injury. Furthermore, the prolactin axis was
upregulated in the neurogenic subventricular zone and dentate gyrus following hypoxia ischemia.
In a spatio-temporal fashion, the increased prolactin and prolactin receptor immunoreactivity was
specifically associated with an increased neuroblast proliferation and migration within the
neurogenic regions. A strong association between the prolactin axis and neuroblast activity was
also seen in neuroblast migration routes. Interestingly, subsequent in vitro studies by T. Gorba in
our laboratory confirmed that PRL has strong and direct proliferative and migratory effects on
neural stem cells.
In summary, these findings show for the first time that the growth hormone and prolactin axes
i
have distinct roles in the injured brain. The growth hormone axis provides neuroprotection
through a distinct neuronal growth hormone receptor. In contrast, the prolactin axis is associated
with glial wound repair responses, post-injury neurogenesis and neuroblast emigration. Since this
prolactin-associated neuroblast activity was bilateral, prolactin may mediate distal processes such
as the transfer of function to the uninjured hemisphere. In conclusion, the growth hormone and
prolactin axes have distinct neuroprotective and restorative roles in the injured brain respectively.
Activation of both systems may therefore benefit neurological outcome following injury. |
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dc.format |
Scanned from print thesis |
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dc.language.iso |
en |
en |
dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA1692211 |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.title |
Protection and recovery of the injured brain the significance of the cerebral growth hormone and prolactin axes |
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dc.type |
Thesis |
en |
thesis.degree.discipline |
Physiology |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
PhD |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.local.anzsrc |
0606 - Physiology |
en |
pubs.org-id |
Faculty of Medical & Hlth Sci |
en |
dc.identifier.wikidata |
Q112868520 |
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