PhD Scientific Days 2025
Budapest, 7-9 July 2025
Poster Session II. - J: Theoretical and Translational Medicine
Chemo- and Radiotherapy Promote Cerebrovascular Senescence, Blood–Brain Barrier Dysfunction and Microhemorrhages in a Preclinical Model of Pediatric Medulloblastoma
Előadó neve
Dr. Nagy Dorina
Előadó munkahelye
Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, OUHSC, OKC, OK, USA
Előadó telefonszáma
06302174896
Előadó e-mail címe
dorinanagy1011@gmail.com
Az előadás címe
Chemo- and Radiotherapy Promote Cerebrovascular Senescence, Blood–Brain Barrier Dysfunction and Microhemorrhages in a Preclinical Model of Pediatric Medulloblastoma
Szerző(k) neve és munkahelye
Dorina Nagy1,2, Boglarka Csik2,3, Kiana Vali Kordestan2,3, Roland Patai2,3, Adam Nyul-Toth2,3, Siva Sai Chandragiri2,3, Rafal Gulej2,3, Raghavendra Y. Nagaraja2,3, Santny Shanmugarama2,3, Shoba Ekambaram2,3, Mark Nagykaldi2,3, Zoltan Benyo1, Zoltan Ungvari2,3, Anna Csiszar2,3
1: Institute of Translational Medicine, Budapest, Semmelweis University
2: Oklahoma Center for Geroscience and Healthy Brain Aging, OUHSC, OKC, OK, USA
3: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, OUHSC, OKC, OK, USA
Bemutatás módja
Poszter
Szekció
Poster Session II. - J: Theoretical and Translational Medicine
Language of the presentation
English
Preferred session
Theoretical and Translational Medicine
Összefoglaló szövege
Introduction: Chemotherapy-induced cognitive impairment is a long-term consequence in survivors of pediatric medulloblastoma, particularly prevalent among those treated with combination chemotherapy (CCT) and cranial radiotherapy (CRT). These survivors face late-onset cerebrovascular complications, such as cerebral small vessel disease, microhemorrhages, and stroke, suggesting a possible vascular contribution to cognitive decline. However, the link between therapy-induced vascular injury and neurocognitive dysfunction is not fully understood. Growing evidence suggests that the accumulation of senescent cells in the cerebral microvasculature impairs blood-brain barrier (BBB) integrity and promotes neurovascular injury.
Aims: To determine whether CCT+CRT accelerates cerebrovascular aging by promoting endothelial and microglial senescence, thereby leading to BBB disruption, cerebral microhemorrhage (CMH) formation, and ultimately, neurovascular dysfunction.
Methods: Transgenic p16-3MR mice, which express red fluorescent protein enabling the identification of senescent cells, received clinically relevant fractionated CRT (5 Gy, twice weekly for 2.5 weeks) and CCT (cisplatin, vincristine, cyclophosphamide) treatment. Senescence in brain endothelial cells and microglia was quantified by flow cytometry. BBB permeability was assessed via intravital two-photon imaging using 40kDa, 3kDa, and 0.3kDa fluorescent dextrans. Since mice do not spontaneously develop CMHs, we used a fluctuating high blood pressure model (angiotensin-II and L-NAME) as a vascular stressor to promote CMH formation. Then, the number, volume, and regional distribution of CMHs were quantified.
Results: Preliminary results of flow cytometry confirmed that CCT+CRT significantly increased endothelial senescence. BBB assessment revealed that CCT+CRT causes severe leakage and structural degradation. CCT+CRT significantly accelerated the onset of neurological signs associated with CMHs, and the number and volume of CMHs were markedly higher in the treated group compared to controls.
Conclusion: CCT+CRT-induced cellular senescence compromises cerebrovascular integrity, leading to BBB breakdown and CMH formation. These therapy-induced changes recapitulate an accelerated aging phenotype that may underlie progressive cognitive impairment in childhood brain tumor survivors.
Funds: NCIR01CA255840
University
Other, please specify in the next box
Other university, not listed above
Univirsity of Oklahoma Health Sciences Center
Supervisor
Anna Csiszar
Publication of my abstract
I give consent to the publication of my abstract on the website of the congress.
phd.section.field
after finishing doctoral studies with absolutorium (PhD)
Kind
Szabad
Status
elfogadva
Accepted presentation method
poszter
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
6925
Start
18:30
End
18:36