Main Session
Sep 28
PQA 03 - Digital Health Innovation and Informatics, Patient Safety & Quality, and Radiation and Cancer Biology

2434 - Regional Radiosensitivity Differences Following Ionizing Radiation in an Ex Vivo 3D Murine Brain Model

10:45am - 12:00pm ET
Poster Hall - Exhibit Hall A
Screen: 8
POSTER

Presenter(s)

M. Dolores De La Mata Moya, MD, PhD, MPH - Centro Medico ABC, Mexico City, CIUDAD DE MEXICO

M. D. De La Mata Moya1, G. Cuamani2, M. Hernandez-Bojorquez3, S. Linares-Melo4, A. Rodriguez4, D. Limon-Perez de Leon5, and K. M. Rubio-Nava6; 1Centro Medico ABC, MEXICO CITY, Mexico, 2Centro Medico ABC, Mexico City, Mexico, 3Centro Médico ABC, Mexico City, DF, Mexico, 4International Laboratory EPIGEN- CONCYTEP- BUAP, Puebla, Mexico, 5BUAP Laboratory of Neuropharmacology, Puebla, Mexico, 6MGH-Harvard Medical School, Boston, MA

Purpose/Objective(s): Preclinical radiation biology models face challenges in replicating environments in vivo to identify precise molecular mechanisms, since 2D cell culture fails to recapitulate in a physiological and biochemical context to the cellular microenvironment. Therefore, 3D tissues (PTCs) give us a platform to assimilate what happens in the body, these retain the anatomical architecture of the organ, metabolic activity, tissue homeostasis and, to some extent, immune functions. In this study, we implemented (PTCs) of irradiated murine brains exposed to clinically ionizing radiation, to evaluate regional differences in radiosensitivity

Materials/Methods: Brains of 4-week-old male Wistar rats, cut to 400µm using a precision vibratome. Grown in 48-well plates with Dulbecco's Modified Eagle's Medium (DMEM) 10% SFB, 1% pen/strep and subsequently irradiated with 2.66 Gy or 3 Gy, with non-irradiated controls. Different anatomical brain regions were identified. Cell viability was estimated using MTT assay.

Results:

PTCs demonstrated region-specific differences in radiosensitivity following ionizing radiation. The fi/ic (fimbria/internal capsule) and DG/CC (Dentate Gyrus/central channel) structures showed a viability reduction of 31-34% after 3 Gy compared to the average of the different regions (Average 1: 35,403, Average 2: 46,590, SD 2,232, 3,444), and an average reduction of 36-41% with 2.66 Gy and a reduction of 36-44% without irradiation. In contrast, the ON/OB (olfactory nu/olfactory bulb) and Cl/ac (Claustrum/anterior commissure) regions, showed a greater decrease of 46-51% in viability with 3 Gy compared with other regions (average 1: 49,589, average 2: 56,899, SD 3,965, 6687), without differences in reduction with 2.66 Gy (31-35%) or control (35-37%). These findings indicate increased radiosensitivity in structures associated with the frontal cortex compared with other brain regions.

Conclusion:

This ex vivo 3D murine brain PTC model exposed to clinically relevant ionizing radiation reveals pronounced regional heterogeneity in radiosensitivity. The model provides a robust platform for studying spatially resolved molecular responses to radiation and offers a foundation for future mechanistic and epigenetic investigations in radiation neurobiology.