Effects of antioxidant U-74389G on a porcine model of intracerebral haemorrhage: Determination of inflammatory markers and crucial enzymes

Doctoral Dissertation uoadl:1308448 332 Read counter

Unit:
Τομέας Βασικών Επιστημών
Library of the School of Health Sciences
Deposit date:
2013-05-27
Year:
2013
Author:
Μπιμπής Αλέξιος
Dissertation committee:
Χαρις Λιάπη, Στυλιανός Τσακίρης, Κωνσταντίνος Βουμβουράκης
Original Title:
Effects of antioxidant U-74389G on a porcine model of intracerebral haemorrhage: Determination of inflammatory markers and crucial enzymes
Languages:
English
Translated title:
Δράση του αντιοξειδωτικού παράγοντα U-74389G, σε πειραματικό πρότυπο ενδοεγκεφαλικού αιματώματος σε χοίρο: Προσδιορισμός παραμέτρων φλεγμονής και σημαντικών ενζύμων
Summary:
Spontaneous intracerebral haemorrhage (ICH) represents a partially understood
cerebrovascular disease of high incidence, morbidity and mortality, accounting
for 10-15% of all strokes. In my study, I investigated the pathophysiological
changes that follow intracerebral haematoma induction on a porcine model of
ICH. The study focused on the determination of changes in tumour necrosis
factor α (TNF-α) and interleukin 1 (IL-1) the first 4 and 24 hrs of ICH as well
as the changes of the crucial enzymes adenosinetriphosphatases (ATPases), in
combination with a study of the effectiveness of the lazaroid antioxidant
U-74389G. Regarding both TNF-α and IL-1, statistically significant increase was
observed in the ipsilateral side of the haematoma as early as 4 hrs and
decrease again 24 hrs after the onset. U-74389G when administered resulted in
statistically significant decrease of TNF-α, (at the heamatoma site in
comparison to the controls) and non statistically significant decrease of IL-1
when compared to the controls. Regarding the ATPases, my study demonstrated
that the examined ICH model does not cause a decrease in Na+,K+-ATPase activity
(the levels of which are responsible for very large part of neuronal energy
expenditure) in the perihaematomal basal ganglia territory, nor a change in the
activity of Mg2+-ATPase. The administration of U-74389G (an established
neuroprotectant) in this ICH model revealed an injury specific type of
behavior, that could be considered as neuroprotective.
I also investigated the role of acetylocholinesterase (AChE; a crucial membrane
bound enzyme involved in cholinergic neurotransmission) in the same porcine
model of spontaneous ICH, with a focus on the first 4 and 24 hrs following the
lesion’s induction, in combination with a study of the effectiveness of the
lazaroid antioxidant U- 74389G administration. My study demonstrates the
activation of AChE activity following U-74389G administration. The lazaroid
U-74389G seems to be an established neuroprotectant and this is the first
report of its supporting role in the enhancement of cholinergic response to the
induction of ICH.
Keywords:
Intracerebral haemorrhage, Lazaroid, Acetylocholinesterase, Na+, K+-ATPase, Tumour Necrosis Factor-α
Index:
Yes
Number of index pages:
21-23
Contains images:
Yes
Number of references:
780
Number of pages:
221
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