Ceftriaxone has a neuroprotective effect in a whole brain irradiation-induced neurotoxicity model by increasing GLT-1 and reducing oxidative stress

Background: Radiation-induced brain injury is an evident side effect of brain irradiation (IR). Often leads to severe and debilitating cognitive dysfunction and neuronal damage. Ionizing radiation results in oxidative and inflammatory processes. Radiation-induced cognitive impairments are also associated with alterations in glutamate composition. Increased release or decreased uptake of glutamate results in dysregulation of neuronal homeostasis, leading to oxidative stress, mitochondrial dysfunctions, and neuroinflammation. Materials: and Methods: Twenty-one rats were taken in the study, and 14 of underwent whole brain IR with a 20 Gray single dose. Ceftriaxone (CTX) treatment was applied in addition to the IR, for 15 days. Animals were divided into three groups. Group1:Normal control; Group2:Placebo(IR-only), Group3:IR+CTX. The one-way ANOVA statistical test was used to compare groups. The value of p<0.05 was accepted as statistically significant. Results: : In addition to the IR applied CTX treatment exhibited a positive impact on the results of the three-chamber sociability test, open field test and passive avoidance learning test, hippocampal CA1, CA3, and Purkinje neuron counts, brain levels of brain-derived neurotrophic factor, Glutamate transporter-1 and Superoxide dismutases activity. As well, CTX decreased the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde and tumor necrosis factor-alpha. Conclusion: Ceftriaxone represented a promising effectiveness on radiation-induced neurocognitive impairments and degradation of social-memory capacity by reducing neuronal loss, oxidative stress, and neuroinflammation in the brain. Also, CTX application induces scavenging of glutamate from the synapses helps to prevent glutamate excitotoxicity, and protects neurons from excitotoxic cell death.