Aquaporins: gatekeepers of oedema in traumatic brain injury.
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Date
2014
Authors
Burton, Joshua Luke
Editors
Advisors
Vink, Robert
Yool, Andrea
Yool, Andrea
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Thesis
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Abstract
[Conclusion] In the present thesis, I have shown that single administration of an AQP4 & 1 antagonist at 5
h, an AQP4 agonist at 48 h and the sequential treatment with both of the compounds at their
optimal time points is beneficial to physiological and functional outcome following diffuse
TBI. At a physiological level there was an attenuation of post traumatic cerebral oedema and
of brain albumin content, with these beneficial effects occurring in the absence of any
changes in water channel expression. Functionally, each compound improved functional
motor outcome after TBI when they were administered at their optimal time point. Sequential
treatment with both compounds proved even more efficacious than single interventions. The
sequential treatment with the antagonist and then the agonist augmented what seemed to be a
protective response of the brain against posttraumatic oedema, namely an initial
downregulation of AQP channels followed by a later upregulation. This alteration in
expression was mimicked by initial inhibition with the antagonist followed by facilitation of
water transport during the resolution phase of oedema. Taken together these results provide
evidence in favour of a pharmaceutical treatment for the attenuation of injury-induced brain
swelling, which when administered at the optimal time points may deliver a much needed
novel, therapeutic intervention for this life threatening condition.
School/Discipline
School of Medical Sciences
Dissertation Note
Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2014
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