S. Y. Ho1, L. T. Shieh2, C. H. Lin1, W. P. Liu3, and C. P. Chang3; 1Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan, 2Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan, 3Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
Purpose/Objective(s): Whole-brain irradiation therapy (WBRT) in rat is associated with increased microglial activation and enhanced phagocytosis, a response that initially serves a neuroprotective purpose by clearing radiation-induced cellular debris. However, prolonged microglial activation transitions into a neurotoxic state, characterized by releasing pro-inflammatory cytokines and increased oxidative stress, exacerbating neural tissue damage. While hyperbaric oxygen therapy (HBOT) has shown benefits in various neurological conditions, its efficacy in addressing radiation-induced brain injury and microglial activation is not well understood. This study investigates the effects of HBOT on neuronal death and microglial activation induced by radiation exposure. Materials/
Methods: A rat model was utilized, receiving varying WBRT doses (0-10 Gy). Rats were categorized into two groups: one undergoing HBOT and the other serving as a control (normal baric air, NBA). HBOT was administered daily for five consecutive days per week over four weeks, starting on the eighth-day post-radiation. Cognitive and motor functions were assessed weekly through behavioral tests. Neuronal death and microglial activation were analyzed on days 7 and 28 post-WBRT using brain tissue samples. Additionally, in vitro studies were conducted on rat primary cortical neurons and microglia in a coculture system to assess the effects of radiation injury (10-30Gy), focusing on neuronal viability, synaptotoxicity, microglial phagocytic capacity, and phenotype. Results: At days 7 and 28 post-WBRT, there was a significant increase in the number of apoptotic neurons within the hippocampus, correlating with enhanced microglial phagocytosis and resulting in cognitive impairments. HBOT effectively improved cognitive functions by attenuating the WBRT-induced neuronal apoptosis and microglial phagocytosis. Moreover, radiation exposure led to axonal injury and diminished viability in cultured primary rat cortical neurons. It similarly affected microglial viability by reducing their phagocytic capacity and increasing the levels of inflammatory mediators, such as TNF-alpha, IL-1 beta, IL-6, iNOS, and COX-2. The radiated microglia displayed a diminished phagocytic capacity and a predominance of CD86+ phenotypes, in contrast to the intact microglia cells, which maintained normal phagocytic capacity and predominantly exhibited CD206+ phenotypes. HBOT normalized cellular death, microglial phagocytosis, and inflammatory responses, including TNF-alpha, IL-1 beta, IL-6, and COX-2 levels. Conclusion: The findings suggest that HBOT significantly alleviates the adverse effects of irradiation-induced brain injury by reducing neuronal apoptosis and microglial activation, highlighting its potential as a therapeutic intervention in managing radiation-induced neurological damage.
