Contributor:

Salińska, Elżbieta (Promotor)

Publisher:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Place of publishing:

Warszawa

Description:

Bibliogr. zawiera 253 pozycje ; 97 s.: il., wykr., fotogr.; 30 cm

Degree name:

doctor

Level of degree:

2

Degree discipline :

medical biology

Abstract:

Hypoxic-ischemic encephalopathy (HIE) results in permanent damage of central nervous system that may lead to neonatal death or developmental disorders. 20-30% of infants with HIE die in the neonatal period, and 33-50% of survivors demonstrate permanent neurodevelopmental abnormalities (such as cerebral paly) and mental retardation.It was shown recently that the group II metabotropic glutamate receptors (mGluR2/3) activation before or after ischemic insult results in neuroprotection but the exact mechanism of this effects is not clear. Neonatal H-I in 7-day-old rats was used as an experimental model of british asphyxia. Rats were injected intra peritoneally with mGluR2 (LY 379268) agonists 1 h or 6 h after H-I (5 mg/kg). The weight deficit of the ischemic brain hemisphere , radical oxygen species (ROS) content levels, antioxidant enzymes activity and the concentrations of reduced glutathione (GSH) were measured. Additionally, the activity of pro-apoptotic enzymes caspase-3 and caspase-9 was measured. The expression of tropphic factors GDNF BDNF, TGF-beta was also measured. Therefore, assuming that the activation of group II mGluRs before H-I may prec=vent ischemic damage and have a neuroprotective effects, we decided to invetigate more closely the molecular mechanism(s) of this effect. The aim of the research was to : 1. determine neuroprotective effects of LY379268 in neonatal rat H-I model, 2. determine the therapeutic window for LY379268 effect, 3. examine the effect of LY 379268 on parameters of oxidative stress, which can be one of the potential factors of neuroprotective action of mGluR2/3 in HI model, 4. determine the effect of LY379268 on apoptotic processes and expression of neurotrophic factors. The main conclusion arising from the results presented in this manuscript is the confirmation that in observed after H-I neuroprotection evoked by LY379268 application, the leading role plays direct effect LY379268 on metabotropic glutamate receptors group II and inhibition of glutamate release that results in decrease of both excitotoxicity and neurodegeneration.

Relation:

Prace doktorskie.

Format:

application/pdf

Resource Identifier:

oai:rcin.org.pl:68295

Source:

IMDiK PAN, call no. ZS 389 ; click here to follow the link

Language:

pol

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego Polskiej Akademii Nauk

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Program Operacyjny Polska Cyfrowa, lata 2014-2020, Działanie 2.3 : Cyfrowa dostępność i użyteczność sektora publicznego; środki z Europejskiego Funduszu Rozwoju Regionalnego oraz współfinansowania krajowego z budżetu państwa

Access:

Open