Radiation-induced Brain Injury and the Protective Role of Oxytetracycline: A Multimodal Study Integrating Behavioral, Biochemical, Histopathological, and Spectroscopic Analyses

Radiation-induced brain injury (RIBI) continues to pose a significant clinical problem linked to neuroinflammation, oxidative stress, and neuronal death. This research evaluates the neuroprotective efficacy of oxytetracycline (OTC) in mitigating RIBI, examining its effects on behavioral, histological, biochemical, and metabolic characteristics. Female Wistar albino rats were categorized into three groups: a control group, a group subjected to brain irradiation with saline, and a group subjected to brain irradiation with oxytetracycline therapy at a dosage of 30 mg/kg/day for 15 days. Behavioral results were assessed through daily sociability, open-field, and passive avoidance learning tests. Biochemical studies included the quantification of inflammatory and oxidative stress indicators, including TNF-α, malondialdehyde (MDA), and superoxide dismutase (SOD). Histopathological assessments focused on neuronal integrity and astrocytic activity in hippocampus (CA1 and CA3 areas) and cerebellar tissues. Magnetic resonance (MR) spectroscopy was used to evaluate metabolic alterations, including lactate, N-acetylaspartate (NAA), and creatine (Cr) concentrations. oxytetracycline therapy markedly decreased oxidative stress indicators, including malondialdehyde (MDA), and restored antioxidant enzyme activity (SOD). Inflammatory markers such as TNF-α, Iba-1, and TLR-4 were reduced, however levels of neurotrophic factors (NGF and NRG-1) remained constant. Improvements in behavior were seen in friendliness, memory retention, and inquisitive behaviors. Histopathological analysis indicated maintained neuronal integrity and diminished GFAP immunostaining in the hippocampus and cerebellum. MR spectroscopy revealed reduced lactate levels and normalized NAA and Cr levels, indicating metabolic stability. Thus, oxytetracycline has neuroprotective properties that act via mitigation of inflammation, decreasing oxidative stress, and maintaining neuronal integrity. Furthermore, its capacity to alleviate metabolic dysfunction enhances its prospective use in safeguarding cognitive and neurological processes. These findings underscore the therapeutic efficacy of oxytetracycline in mitigating radiation-induced cerebral damage.