Related Experiment Videos
Induction of acute phase gene expression by brain irradiation
J H Hong1, C S Chiang, I L Campbell
1Department of Radiation Oncology, UCLA School of Medicine 90095, USA.
International Journal of Radiation Oncology, Biology, Physics
|October 15, 1995
Summary
Ionizing radiation triggers an acute inflammatory gene response in the brain, with key molecules like TNF-alpha and IL-1 beta increasing post-irradiation. This inflammatory cascade likely underlies early radiotherapy symptoms and is partially suppressed by dexamethasone and pentoxifylline.
Area of Science:
- Neuroscience
- Radiation Biology
- Molecular Biology
Background:
- Ionizing radiation exposure can induce complex biological responses in the central nervous system.
- Understanding the molecular mechanisms underlying brain's reaction to radiation is crucial for managing radiotherapy side effects.
Purpose of the Study:
- To investigate the in vivo acute phase molecular response of the brain to ionizing radiation.
- To identify specific genes and pathways involved in the brain's immediate reaction to radiation exposure.
Main Methods:
- Mice (C3Hf/Sed/Kam) underwent midbrain or whole-body irradiation with varying doses.
- Cerebral gene expression of cytokines (ILs, TNF-alpha/beta), adhesion molecules (ICAM-1), and other markers (iNOS, vWF, EB22/5.3, GFAP) was measured using ribonuclease protection assay.
- The impact of dexamethasone and pentoxifylline treatments on radiation-induced gene expression was evaluated.
Main Results:
- Irradiation increased messenger RNA levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3, IL-1 alpha, and GFAP in the brain, dose-dependently.
- Responses were generally rapid (peaking within 4-8 hours), with exceptions like EB22/5.3 and GFAP showing delayed elevation.
- Dexamethasone and pentoxifylline partially or completely suppressed radiation-induced gene expression, with dexamethasone being more potent.
Conclusions:
- The brain's initial response to irradiation involves the expression of inflammatory gene products.
- These inflammatory mediators are likely responsible for early clinical symptoms observed after brain radiotherapy.
- The findings support the clinical use of steroids to mitigate radiation-induced brain injury.