prikaz prve stranice dokumenta Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury
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doctoral thesis
Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury
2021. urn:nbn:hr:193:651606
Petrović, Antonela
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Petrović, A. (2021). Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury (Doctoral thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:651606

Petrović, Antonela. "Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury." Doctoral thesis, University of Rijeka, 2021. https://urn.nsk.hr/urn:nbn:hr:193:651606

Petrović, Antonela. "Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury." Doctoral thesis, University of Rijeka, 2021. https://urn.nsk.hr/urn:nbn:hr:193:651606

Petrović, A. (2021). 'Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury', Doctoral thesis, University of Rijeka, accessed 29 October 2024, https://urn.nsk.hr/urn:nbn:hr:193:651606

Petrović A. Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury [Doctoral thesis]. Rijeka: University of Rijeka; 2021 [cited 2024 October 29] Available at: https://urn.nsk.hr/urn:nbn:hr:193:651606

A. Petrović, "Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury", Doctoral thesis, University of Rijeka, Rijeka, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:193:651606

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Metadata
TitleRevealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury
Title (english)Revealing molecular and cellular mechanisms involved in neuroprotection and neuroregeneration after central nervous system injury
AuthorAntonela Petrović
MentorMiranda Mladinić Pejatović (mentor)
Committee memberNicholas James Bradshaw (predsjednik povjerenstva)
Committee memberDubravka Švob Štrac (član povjerenstva)
Committee memberAntonija Jurak Begonja (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2021-09-09, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
The inability of adult mammals to regenerate central nervous system (CNS) after injury is one of the greatest challenges of modern neuroscience, which has not yet revealed how to fully restore the lost functions of damaged neuronal tissue in the brain and spinal cord.To address this problem, we established two new experimental in vitro models suitable for CNS injury research: in vitro culture of neonatal rat spinal cord tissue with longer period of viability (more than 24h), in which we investigated molecular and cellular mechanisms of neurodegeneration and neuroprotection, and primary cortical cell cultures derived from postnatal opossums, to investigate CNS development and the possibility of its regeneration after mechanical or pharmacological experimental injury. The main goal of the research was to discover key cellular and molecular mechanisms that control and enable neuroprotection and neuroregeneration of the mammalian CNS, in order to develop new strategies for treatment of CNS injuries.The results of the study showed that the heat shock protein HSP70 plays a major role in the survival of motoneurons after experimental rat spinal cord injury in vitro and thus has a neuroprotective effect. Therefore, we pharmacologically induced HSP70 expression and confirmed early protection of motoneurons during acute in vitro rat spinal cord injury. Furthermore, the results of the neuroregeneration studies on neonatal opossums indicated that transcription factor ATF3 plays an important role in control of maturation of mammalian neural progenitor stem cells, and that, consequently, ATF3 is an important factor in regeneration of brain neurons of young opossum after injury. The overall achievements of this study could, in future, allow the development of new neuroprotective strategies for the treatment of mammalian brain and spinal cord injuries, as well as new strategies to promote neuroregeneration of mammalian CNS, which lose this ability during early embryonic or postnatal development.
Abstract (english)
Nemogućnost odraslih sisavaca da regeneriraju središnji živčani sustav (SŽS) nakon ozljede jedan je od najvećih izazova suvremene neuroznanosti koja još uvijek nije odgovorila na pitanje kako u potpunosti vratiti funkciju oštećenog živčanog tkiva mozga i leđne moždine. Kako bi pridonijeli rješavanju ovog problema, uspostavili smo dva nova eksperimentalna in vitro modela pogodna za istraživanje ozljeda SŽS-a: dugotrajnu (više od 24h) in vitro kulturu tkiva leđne moždine neonatalnog štakora na kojoj smo istraživali molekularne i stanične mehanizme neurodegeneracije i neuroprotekcije, te primarne stanične kulture korteksa postnatalnog oposuma koje smo koristili za istraživanje razvoja SŽS, te mogućnosti njegove regeneracije nakon eksperimentalne mehaničke ili farmakološke ozljede. Glavni cilj istraživanja bio je otkrivanje ključnih staničnih i molekularnih mehanizama koji kontroliraju i omogućuju neuroprotekciju i neuroregeneraciju SŽS-a sisavaca, kako bi se razvile nove strategije liječenja ozljeda istoga. Rezultati istraživanja pokazali su da protein toplinskog šoka HSP70 igra jednu od glavnih uloga u preživljavanju motoneurona nakon eksperimentalne ozljede leđne moždine štakora in vitro te da stoga ima neuroprotektivno djelovanje. Farmakološki smo stoga inducirali ekspresiju HSP70 i potvrdili ranu zaštitu motoneurona tijekom akutne ozljede tkiva leđne moždine štakora in vitro. Nadalje, rezultati istraživanja neuroregeneracije SŽS-a oposuma ukazali su da transkripcijski faktor ATF3 ima važnu ulogu u kontroli sazrijevanja neuralnih matičnih praroditeljskih stanica sisavaca, te posljedično da je važan čimbenik u regeneraciji moždanih neurona mladih oposuma nakon ozljede. Sveukupna postignuća ovog istraživanja mogla bi u budućnosti omogućiti razvoj novih neuroprotetivnih strategija za tretman ozljeda mozga i leđne moždine sisavaca, kao i novih strategija koje bi potaknule neuroregeneraciju SŽS-a sisavaca, koji tu sposobnost gube tijekom ranog embrionalnog ili postnatalnog razvoja.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:193:651606
Promotion2021
Study programmeTitle: Medicinal chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini (doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini)
Type of resourceText
File originBorn digital
Access conditionsClosed access
Terms of useLicence In copyright icon
Created on2021-12-16 11:21:18