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Updated: Sep 3, 2025

Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Physical Training Protects Against Brain Toxicity in Mice Exposed to an Experimental Model of Glioblastoma
Amanda K Costa1, Luis F B Marqueze1, Bruna B Gattiboni1
1Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, Tech Park - Block 4, Laboratory 3. Imaculada Conceição Street, 1155, Prado Velho, Curitiba, PE, 80215-901, Brazil.
Abstract:
Glioma 261 (Gl261) cell-mediated neurotoxicity has been reported in previous studies examining glioblastoma (GBM), and the effects of physical exercise (PE) on this neurotoxicity have been poorly investigated. This study aimed to evaluate the effects of a PE program in animals with experimental GBM. Male C57BL/6J mice were randomized into sham or GBM groups and subjected to a PE program for four weeks. Gl261 cells were administered into the intraventricular region at 48 h after the last exercise session. Body weight, water and feed consumption, and behavior were all evaluated for 21 days followed by euthanasia. The right parietal lobe was removed for the analysis of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), vimentin, C-myc, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), hydrogen peroxide, the glutathione system, and oxidative damage to proteins. The results revealed changes in the behavioral patterns of the trained animals, and no anatomopathological changes were observed in response to PE training. In contrast, animals with GBM subjected to PE exhibited lower immunoexpression of c-MYC, vimentin, and GFAP. Although experimental GBM altered the redox profile and inflammatory mediators, no significant alterations were observed after PE. In conclusion, our data provide consistent evidence of the relationship between PE and the improvement of tumorigenic parameters against the neurotoxicity of GL261 cells.
Insights
Physical exercise (PE) may improve outcomes in experimental glioblastoma (GBM). This study found PE reduced specific tumor markers and altered behavior in mice with GBM, suggesting a beneficial role for exercise in managing brain tumors.
Area of Science:
- Neuroscience
- Oncology
- Exercise Physiology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor associated with neurotoxicity.
- The impact of physical exercise (PE) on GBM-induced neurotoxicity remains largely unexplored.
- Experimental models like Glioma 261 (Gl261) cells offer insights into GBM pathogenesis.
Purpose of the Study:
- To investigate the effects of a structured physical exercise program on experimental glioblastoma (GBM) in mice.
- To assess the influence of PE on neurotoxicity, behavioral changes, and specific molecular markers associated with GBM.
- To evaluate the interplay between physical activity and the tumor microenvironment in a preclinical GBM model.
Main Methods:
- Male C57BL/6J mice were assigned to sham or GBM groups and underwent a four-week PE program.
- Gl261 cells were stereotactically injected into the intraventricular region post-exercise.
- Evaluations included body weight, consumption, behavior, and post-mortem analysis of brain tissue for molecular markers (GFAP, EGFR, vimentin, c-MYC, NF-κB, cytokines, oxidative stress markers).
Main Results:
- PE induced behavioral changes in mice but did not cause adverse anatomopathological effects.
- Mice with GBM that underwent PE showed reduced immunoexpression of c-MYC, vimentin, and glial fibrillary acidic protein (GFAP).
- While GBM affected the redox profile and inflammatory mediators, PE did not significantly alter these parameters.
Conclusions:
- Physical exercise demonstrates a potential role in improving tumorigenic parameters in the context of experimental GBM.
- PE may modulate specific molecular markers associated with GBM progression and neurotoxicity.
- Further research is warranted to elucidate the mechanisms underlying PE's effects on brain tumors.

