Fullerene derivatives reduce brain inflammation after cranial radiation therapy

Researchers at the University of Texas Health Science Center in Houston have demonstrated that a water-soluble derivative of [60]fullerene, known as C60-ser, can mitigate cognitive decline and neuroinflammation in mice following cranial radiation therapy. This carbon nanomaterial, with its unique radical-scavenging properties, was shown to restore spatial working memory and suppress chronic brain inflammation when administered 24 hours after irradiation. The findings, published in Biomedical Microdevices, suggest that C60-ser could be a promising candidate for protecting the brains of cancer patients undergoing radiotherapy.

Cranial radiation therapy, a common treatment for brain tumors, often results in cognitive impairments due to the exposure of healthy brain tissue to ionizing radiation. This exposure generates free radicals and reactive oxygen species, leading to an inflammatory cascade that activates microglia and other immune cells, perpetuating damage. The study highlights the potential of C60-ser to intercept this cascade by neutralizing oxidative stress, thereby preventing long-term cognitive deficits.

The research team, led by Naren Gundapaneni, Yuri Mackeyev, and Sunil Krishnan, developed C60-ser through a two-step chemical synthesis process that enhances its solubility and bioavailability. This derivative crosses the blood-brain barrier and remains in brain tissue for over a week, making it an effective agent for targeting radiation-induced damage. Behavioral tests on irradiated mice showed significant improvements in spatial working memory when treated with C60-ser, particularly at higher radiation doses.

Histological analysis revealed that C60-ser significantly reduced the activation of microglia in the hippocampus, a key area for memory formation. This reduction in neuroinflammation supports the compound's role in protecting cognitive function. The study's implications extend beyond oncology, as C60-ser may also serve as a radioprotective agent for astronauts exposed to cosmic radiation on long-duration space missions.

Future research will focus on optimizing the dosage of C60-ser, exploring its effects in female subjects, and evaluating its potential in combination with other emerging radiotherapy modalities. The researchers have filed a provisional patent for C60-ser, indicating their intention to advance this compound towards clinical application.