Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011
DOI:
https://doi.org/10.2298/ABS210129011KKeywords:
Rat brainstem, Irradiation, Radioprotector GL2011, Raman microspectroscopy, glial cell markers, cytokinesAbstract
Paper description:
- We studied a novel radioprotector, GL2011 on the molecular and cellular signatures of neuroinflammation in surviving Wistar rats with focus on the brainstem.
- Raman microspectroscopy served to follow the molecular changes on gamma-irradiated rat brainstem tissue, immunohistochemistry the response of neuroglia, and global inflammation was examined by screening cytokines (IL-6, TNF-α, IL-10) in blood plasma.
- GL2011 mitigated the effect of radiation on nucleic acids and preserved astrocyte and microglia morphology, decreasing microglial infiltration in the brainstem. A global immunomodulatory effect was observed.
- Application of the radioprotector after radiation confers better protection, suggesting translation to treatment of radiation accidents.
Abstract: The search for an effective and non-toxic radioprotector is ongoing. We tested a novel, natural aminothiol-based radioprotector, GL2011, that was applied 30 min, 3 h or 6 h after the exposure of male albino Wistar rats to a 6.7 Gy mild dose of gamma radiation. The molecular signatures of radioprotection were investigated with Raman microspectroscopy of brainstem tissue samples. Morphological changes and activation of astrocytes and microglia were assessed by immunohistochemistry. Global markers of neuroinflammation were followed by ELISA to monitor blood plasma levels of proinflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines. A thirty-day follow-up determined survival of unprotected animals 37.5%. A survival increase was observed after radioprotection (75%, irrespective of the time of application). Raman spectra revealed a slightly deleterious effect of radiation on nucleic acids in surviving animals that was mitigated with the radioprotector, as GL2011 preserved the morphology of both astrocytes and microglia, with reduced microglial infiltration. Cytokine assessment revealed an immunomodulatory effect of the novel radioprotector. The overall results point out the positive effects of a single dose of GL2011 applied at different times. The molecular and cellular changes in the brainstem indicate that the radioprotector applied after radiation conferred better protection, which underlines its translation to cure radiation accidents.
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